Int J Cardiovasc Imaging DOI 10.1007/s10554-013-0355-y
ORIGINAL PAPER
Evaluation of apical pouches in hypertrophic cardiomyopathy using cardiac MRI Kalie Y. Kebed • Raed I. Al Adham • Kalkidan Bishu • J. Wells Askew • Kyle W. Klarich • Jae K. Oh • Paul R. Julsrud • Thomas A. Foley • James F. Glockner • Rick A. Nishimura • Steve R. Ommen • Nandan S. Anavekar
Received: 7 October 2013 / Accepted: 23 December 2013 Ó Springer Science+Business Media Dordrecht 2014
Abstract The presence of apical pouches in hypertrophic cardiomyopathy (HCM) may portend poor prognosis. We sought to study if the use cardiac magnetic resonance imaging (CMR) improves the detection of apical pouches in HCM compared to echocardiography. A retrospective review was performed of all consecutive HCM patients with an apical pouch identified by CMR at Mayo Clinic from May 2004 to Sept 2011. Clinical data was abstracted and CMR and echocardiographic images were analyzed. There were 56 consecutive HCM patients with an apical pouch identified by CMR. The predominant morphological type was apical in 41 (73.2 %), followed by sigmoid in 6 (10.7 %), reversed curve in 6 (10.7 %) and neutral in 3 (5.4 %). Obstructive physiology or systolic anterior motion of the mitral valve leaflet was evident in 23 (41.1 %). Late gadolinium enhancement was present in 47 (87.0 %) patients. Apical pouches were detected in only 18 (32.1 %) patients on echocardiography. Even when intravenous contrast was used (29/56 patients), in 16/29 (55.2 %)
K. Y. Kebed (&) Department of Internal Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA e-mail: [email protected] R. I. Al Adham Department of Internal Medicine, St. Joseph’s Hospital, Phoenix, AZ, USA K. Bishu J. W. Askew K. W. Klarich J. K. Oh R. A. Nishimura S. R. Ommen N. S. Anavekar Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA P. R. Julsrud T. A. Foley J. F. Glockner Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
pouches were missed on echocardiography. Pouch length and neck dimensions in systole and diastole, measured on CMR, were larger among those patients in whom pouches were detected on echocardiography suggesting only larger pouches can be identified on echocardiography. In the largest CMR series to date of apical pouches in HCM, we show that while apical pouches are most commonly seen in apical HCM, they can be found in other phenotypic variants. CMR is better suited for the evaluation of apical pouches compared to echocardiography even with the use of intravenous contrast. CMR is likely a better tool for evaluating the cardiac apical structures including apical pouches when clinically indicated. Keywords Apical pouches Hypertrophic cardiomyopathy Cardiac MRI Echocardiography Abbreviations HCM Hypertrophic cardiomyopathy LV Left ventricle SCD Sudden cardiac death ICD Implantable cardioverter-defibrillator CMR Cardiac magnetic resonance NSVT Non-sustained ventricular tachycardia LVOT Left ventricular outflow tract SAM Systolic anterior motion SSFP Steady state free precession LGE Late gadolinium enhancement
Background Hypertrophic cardiomyopathy (HCM), a relatively common genetic cardiovascular disease, is characterized by a hypertrophied, non-dilated left ventricle (LV) in the absence of
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other diseases capable of explaining the extent of hypertrophy. HCM is phenotypically classified into four morphological subtypes (apical, sigmoid, reversed curve, and neutral) [1, 2]. Within the diverse phenotypic spectrum of HCM, a subset of patients with apical pouches has been described, with a reported prevalence of 2 % [3]. Proposed mechanisms for the development of apical pouches have included LV wall stress secondary to mid-cavitary obstruction and genetic predisposition [4–8]. Earlier studies have suggested a poor prognosis in patients with apical pouches [3, 9–11]. Maron et al. [3] reported a combined adverse event [sudden cardiac death (SCD), appropriate implantable cardioverter-defibrillator (ICD) discharges, nonfatal thromboembolic stroke, progressive heart failure and death] rate of 10.5 % per year in HCM patients with apical pouches. The presence of an apical pouch has thus been identified as an SCD risk modifier in the latest HCM guidelines [12]. More data is needed to determine the best way to diagnose apical pouch so that further clinical assessments regarding the benefits of anticoagulation and surgical resection can be assessed more accurately. Given the prognostic implications, accurate identification of apical pouches is important for counseling patients on the expected risks and future investigations regarding the clinical implication of apical pouches. We aim to characterize cardiac magnetic resonance (CMR) findings of apical pouches in HCM and determine the incremental diagnostic value of CMR.
Methods Patient selection This was a retrospective review of 56 consecutive HCM patients with an apical pouch identified by CMR at Mayo Clinic from May 2004 to Sept 2011. Apical pouches were defined as an area of wall thinning and dyskinesis involving the LV apex. CMR and echocardiographic images were analyzed to determine pouch size and incremental diagnostic value of CMR. The study was approved by the Mayo Clinic Institutional Review Board. Clinical data Clinical and demographic data from the electronic medical records at the time of CMR study was abstracted. This included age, gender, ethnicity, genotype, and structural subtype. Co-morbidities included hypertension; diabetes mellitus; coronary artery disease, defined by either angiographically (invasive or CT) proven 50 % stenosis or prior myocardial infarction; history of atrial fibrillation; and history of syncope. First-degree family history of HCM
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and SCD were recorded. Presence of severe symptoms was defined as the presence of either New York Heart Association class C3 dyspnea or Canadian Cardiovascular Society angina class C3. ECG and Holter monitoring Additional data was abstracted in patients with ECG and Holter monitoring within 6 months of CMR. ECGs were examined for PR, QRS and QT interval duration, ST segment and T wave changes, presence of bundle branch block and atrial fibrillation. Holter reports were examined for the presence of total ventricular beats, ventricular couplets or bigeminy, and number of non-sustained ventricular tachycardia episodes (NSVT) defined as 3 or more consecutive ventricular beats. Echocardiography Two-dimensional echocardiograms performed within 6 months of the CMR study were reviewed in each patient. Magnitude and distribution of LV hypertrophy, intracavitary and LV outflow tract (LVOT) velocities, strain rate analysis, and presence or absence of apical pouches and thrombus were recorded. A single reviewer (K.B.), blinded to clinical and CMR data, reviewed the echocardiograms. Cardiac MRI Cardiac magnetic resonance studies were reviewed for magnitude and distribution of LV hypertrophy, apical pouch, thrombus, LVOT obstruction, systolic anterior motion (SAM) of the mitral valve, and late gadolinium enhancement (LGE) presence and distribution. Apical pouch anatomy and dimensions; LV ejection fraction, LV end-systolic and end-diastolic diameters and volumes, LV end-diastolic mass, and maximal (end diastolic) septal thickness were analyzed using steady state free precession (SSFP) sequences in multiple imaging planes. The product delayed enhancement sequence that was used to assessment of myocardial viability is a conventional 2D inversion recovery gradient echo pulse sequence. A double dose of gadolinium (0.2 mol/kg) was infused, and LGE imaging occurred at approximately 10 min after the administration of contrast. Apical pouch anatomy was best demonstrated in long axis views including the two, three and four chamber views. Volumetric and mass data were recorded from the short-axis imaging plane. A single reviewer (N.A.), blinded to clinical and echocardiography data, reviewed the CMR studies and measured the apical pouch dimensions. Pouch measurements were made on the Advantage Workstation. A single reviewer (N.A.) performed the MRI
Int J Cardiovasc Imaging Table 1 Clinical features of the study patients Variables
Table 2 Electrocardiographic finding of the study patients
Value
n
Demographics Age, years
57.5 ± 16.5
Atrial Fibrillation (ECG) n (%)
4 (7)
56
Atrial Fibrillation (History) n (%)
13 (23)
56
PR interval (ms)
172 ± 29
52 56
31 (55.4)
56
Ethnicity, white n (%)
42 (85.7)
49
Risk factors and comorbidities Diabetes mellitus (%) Coronary artery disease, angiographic (%) Prior myocardial infarction
n
56
Gender, male n (%)
Hypertension n (%)
Apical pouches
QRS interval (ms)
105 ± 26
QTc interval (ms)
450 ± 65
56
Axis, degree
24 ± 33
56
26 (46.4)
56
3 (5.4)
56
ST depression C 1 mm n (%)
15 (27)
56
56
T-wave inversion C 5 mm n (%)
33 (59)
56
56
T-wave inversion C 10 mm n (%)
9 (16)
56
14 (25) 7 (12.5)
Atrial fibrillation (%)
13 (23.2)
56
Positive T-wave C 10 mm n (%)
2 (4)
56
Syncope (%) Severe symptoms (%)
4 (7.1) 23 (41.1)
56 56
Abnormal Q-wave n (%) RBBB n (%)
0 (0) 1 (2)
56 56
LBBB n (%)
6 (11)
56
First degree relative with HCM (%)
8 (14.3)
56
Sudden cardiac death in first degree relative (%)
1 (1.8)
56
Results measurements twice per study. The pouches were identified on the clinical report. The long dimension was from the tip of the pouch to the neck and the transverse dimension across the neck of the pouch at systole and diastole. Reproducibility of the measurement was not performed but the measurements were systematically larger than that recorded on echocardiography by a blinded second reviewer (K.B.). The difference between two different modalities was the goal of the measurements since the size of the apical pouches is not routinely reported on the clinical reports. For this reason, our group did not think that it was necessary to perform procedures to test the reproducibility of the measurement. LGE enhancement was taken from the clinical report and did not use any automated software to ascribe a threshold for enhancement. All studies were performed on a 1.5-Tesla MRI scanner (Signa Twin Speed Excite, General Electric, Waukesha, Wis).
Clinical and demographic features
Statistical analysis
Electrocardiography and holter monitoring
Mean ± standard deviation or number (frequency) are presented to summarize data for continuous and nominal variables, respectively. Pouch length and neck dimensions in systole and diastole were compared using independent, two-sample t tests. Pearson’s Chi square test was used to compare the proportion of use of intravenous contrast among patients in whom pouches were diagnosed and missed on echocardiography. Fisher’s exact test was used to compare the proportion of patients with LGE on CMR and detection of a pouch on echocardiography as 2 cells had expected counts [5. p \ 0.05 was considered statistically significant. Analysis was performed using IBM SPSS Statistics software Version 19 (Armonk, NY).
ECGs at the time of the CMR were available in all patients, and the results are summarized in Table 2. Mean PR, QRS, and QTc intervals were 172 ± 29, 105 ± 26 and 450 ± 65 ms, respectively. Of the 13 (23 %) patients with a history of atrial fibrillation, 4 (7 %) were in atrial fibrillation at the time of ECG study. ST depression was present in 15 (27 %). T wave inversions C5 and C10 mm were seen in 33 (59 %) and 9 (16 %), respectively. None had abnormal Q waves. Right bundle branch block was present in 1 (2 %). Left bundle branch block was present in 6 (11 %). A 24-hour Holter ECG was performed in 42 patients. Of these, 11 (26.2 %) had C1 run of NSVT. Mean total
There were 817 consecutive patients evaluated at our center with echo and CMR with a diagnosis of HCM at the Mayo Clinic (Rochester, MN) from May 2004 to Sept 2011. Of these, there were 56 (6.9 %) patients with an apical pouch identified by CMR. Demographics and comorbidities are summarized in Table 1. Mean age was 57.5 ± 16.5 years, 31 (55.4 %) were male, and 42 (85.7 %) were Caucasian. Comorbidities included hypertension in 26 (46.4 %), diabetes mellitus in 3 (5.4 %) and atrial fibrillation in 13 (23.2 %) patients. Coronary artery disease was present in 14 (25.0 %), and 7 (12.5 %) patients had a prior myocardial infarction. A history of syncope was reported in 4 (7.1 %) while 23 (41.1 %) patients had severe symptoms. There was known family history of HCM in 8 (14.3 %), and 1 (1.8 %) has SCD in a first degree relative.
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Int J Cardiovasc Imaging Table 3 Echocardiography findings of the study patients Variables
Value
Available
Septal thickness (mm)
15.5 ± 4.8
54
Posterior wall thickness (mm)
13.1 ± 3.2
53
Ejection fraction (%)
69.3 ± 7.0
55
LVOT velocity resting (m/s)
1.9 ± 1.4
42
Basal Strain average (%)
-7.2 ± 15.5
24
Mid Strain average (%)
-4.3 ± 11.9
25
Apical Strain average (%)
-4.8 ± 7.9
18
Average LV strain (%)
-7.7 ± 7.4
16
Apical pouch (%)
18 (32)
56
Apical thrombus (%)
1 (2.2)
46
Table 4 CMR findings of the study patients Variables
Value
n
LV EF (%)
67.1 ± 9.9
56
LV end diastolic volume (ml)
131.7 ± 34.6
55
LV end systolic volume (ml)
44.1 ± 19.5
55
Maximal thickness (mm)
21.5 ± 4.5
44
Apical pouch length in diastole (mm)
15.7 ± 7.5
56
Apical pouch neck in diastole (mm)
17.0 ± 8.4
56
Apical pouch length in systole (mm)
18.2 ± 10.8
56
Apical pouch neck in systole (mm)
17.2 ± 10.4
56
Obstructive physiology or SAM (%)
23 (41)
56
Systolic anterior motion of mitral valve leaflets (%)
19 (34)
56
Late gadolinium enhancement (LGE) n (%)
47 (87)
54
Apical pouch n (%)
56 (100)
56
Apical Thrombus n (%)
2 (3.6)
56
ventricular beats was 402 ± 1682 and ventricular couplets or bigeminy was 9.3 ± 45.9.
Fig. 1 Compares the pouch dimensions measured on CMR between those patients with prior diagnosis of apical pouch on echocardiography (black bars) and those with apical pouches only diagnosed on CMR (white bars). The dimension standard deviations are represented by the thin ‘‘T’’ lines. The y-axis is length measured in millimeters. Compared using independent, two-sample t tests. p \ 0.05 comparing dimensions measured on CMR between patients in which pouch was and was not seen on echo
Cardiac MRI The CMR findings are summarized in Table 4. On CMR, the predominant morphological type was apical in 41 (73.2 %), followed by sigmoid in 6 (10.7 %), reversed curve in 6 (10.7 %) and neutral in 3 (5.4 %). LV ejection fraction was 67 ± 10 %, range 45.0–79.0 %. LV end-diastolic and end-systolic volumes were 131.7 ± 34.6 and 44.1 ± 19.5 ml, respectively. Maximum LV thickness was 21.5 ± 4.5 mm. Obstructive physiology or SAM was evident in 23 (41.1 %) patients. LGE was present in 47 (83.9 %) patients. Of those 47, the distribution involved the apex in 28 (77.8 %) patients. The mean pouch length was 15.7 ± 7.5 and 18.2 ± 10.8 mm in diastole and systole, respectively. The mean pouch neck was 17.0 ± 8.4 and 17.2 ± 10.4 mm in diastole and systole, respectively. Thrombus was present in 2 (3.6 %) of pouches. The diagnostic value of echocardiography and CMR
Echocardiography All 56 patients had an echocardiogram performed within 6 months of the CMR study. Intravenous contrast (Definity or Optison) was used in 29 (52 %) patients. The echocardiography findings are summarized in Table 3. Apical pouches were detected in 18 (32.1 %) patients. Of the 18 apical pouches detected, 13 examinations utilized intravenous contrast agent. The pouch length was 20.2 ± 6.4 and 18.1 ± 5.9 mm in diastole and systole, respectively. The pouch neck was 13.0 ± 4.3 and 10.2 ± 3.6 mm in diastole and systole, respectively. Echocardiography detected thrombus in 1 apical pouch.
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All the pouches seen on echocardiography were also demonstrated on CMR. Patients in whom pouches were detected on echocardiography had larger measured pouch dimensions on CMR. The pouch length in diastole was 18.3 ± 6.0 and 14.4 ± 7.9 mm in those seen on echocardiography versus those that were missed, respectively (p \ 0.05). Likewise, the pouch length in systole was 24.9 ± 8.0 and 15.5 ± 10.9 mm, respectively (p \ 0.05). The pouch neck in diastole was 20.8 ± 7.6 and 15.1 ± 8.2 mm, respectively (p \ 0.05). The pouch neck in systole was 23.3 ± 8.0 and 14.4 ± 10.2 mm, respectively (p \ 0.05). These findings are summarized in Fig. 1. Intravenous contrast was
Int J Cardiovasc Imaging
Discussion
Fig. 2 CMR steady state free precession four chamber view demonstrating apical HCM with an apical pouch
Fig. 3 Echo 2D apical long axis view without contrast enhancement demonstrating abnormal LV wall thickness
used in 13 of 18 (72.2 %) patients who had pouches detected on echocardiography while 16 of 38 (42.1 %) of patients in whom pouches were missed on echocardiography had used intravenous contrast (p = 0.16). Of the 29 patients receiving contrast, 16 (55.2 %) of pouches were not detected on echocardiography. Figure 2 is a CMR SSFP four chamber view demonstrating apical HCM with an apical pouch that was not seen on Fig. 3, the corresponding echo 2D apical long axis view. The finding of LGE was not associated with identification of apical pouch on echo. 2 (11 %) of those with pouches found on echo had LGE whereas 5 (14 %) of those with pouches not detected on echo had LGE (p = 0.6).
This study is the largest series of apical pouches in the current literature demonstrating, primarily anatomic features of apical pouches, and secondarily differences in their identification comparing CMR and echocardiographic imaging modalities. We have demonstrated a much higher prevalence of apical pouches (6.9 %) than previously reported in predominately echocardiographic studies. In a large study reporting a prevalence of 2.2 %, only 22 of 1299 patients were evaluated with CMR [3]. Similarly, in a purely echocardiography study, true apical pouches were seen in 6 of 193 patients (3.1 %) [13]. Our higher prevalence is a reflection of the superiority of CMR in detecting apical pouches. Given the clinical implications of apical pouches, specifically their relation to SCD and the role of adjunctive medical therapies, this study provides novel insight regarding imaging evaluation. The main findings of this study suggest that CMR is superior to echocardiography in the identification and qualification of apical cardiac structures, even after accounting for echocardiographic techniques used to enhance endocardial border definition. The genotypic and phenotypic expression in HCM is wide, and there is an underappreciated subset with thin walled apical pouches seen typically in apical HCM. Echocardiography is the standard imaging modality in HCM, although, CMR is emerging as a valuable adjunct that is primarily used to assess for LGE but may have an equally important role in detecting apical pouches. CMR is recommended in patients with known HCM when additional information may have an impact on management [14–16]. Some authors have suggested that CMR provides more accurate information on LV morphology [14] and is superior in detecting apical pouches. In recent studies, nearly one in two apical pouches seen on CMR were undetected by prior echocardiography [3, 17, 18]. In 2008, Maron et al. [3] identified 28 HCM patients with apical pouches using CMR, 12 (43 %) of which were undetected by echocardiography. In 2010, Fattori et al. [18] studied 13 apical HCM patients, 9 with prior echocardiographic diagnosis of apical HCM and 4 with normal or inconclusive results. Apical pouch was identified in 4 (31 %) patients on CMR, three (75 %) of which were not seen on prior echocardiography. In 2012, Kim et al. [17] published a report of 40 apical HCM patients and discovered 5 (12.5 %) with apical pouches on CMR, 3 (60 %) of which were not seen on routine echocardiography. A poor prognosis with SCD in patients with apical pouches has been reported [3, 9–11], although, more recent studies suggest a more favorable prognosis [13, 17]. In the aforementioned study published by Maron et al. 12
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(43 %) apical pouch patients experienced adverse disease complications with a combined adverse event rate of 10.5 % per year. Greater than 40 % of patients with SCD or appropriate ICD discharges had 0 of the 5 conventional primary prevention risk factors, suggesting apical pouch formation might be a novel, independent risk factor. This led to the updated guidelines recognizing apical pouches as potential SCD risk modifier [3, 12]. In the 5 apical pouch patients reported by Kim et al. [17] at 2 year follow-up, no patient had the composite endpoint of SCD, all-cause mortality, or hospitalization for heart failure. Binder et al. [13] studied 193 apical HCM patients, of which 29 patients had a spectrum of apical outpouching identified on echocardiography. Overall mortality, SCD, and ICD discharge events were not more common in patients with apical outpouching. Although the recent prognostic data initially appears conflicting, the methodologies of the studies have key differences that need to be accounted for. Kim et al. had a very small sample size (n = 5) and a short 2 year follow-up period preventing definitive conclusions regarding prognosis. Maron et al. followed the clinical course of all identified apical pouch patients regardless of morphology, whereas the Binder et al. analysis compared apical HCM patients with and without pouches and excluded those with LVOT obstruction, an accepted SCD risk modifier [12, 19, 20]. The literature in its entirety is based on small sample sizes, and more data is needed to clarify the prognosis. Further, there is a paucity of data on the therapeutic implications of apical pouches, and there is no consensus on the role of anticoagulation and prophylactic surgical resection, which is currently managed on a case-by-case basis. Given the potential prognostic implications, identification of apical pouches is important for counseling and management of HCM patients. To characterize the findings of apical pouches and determine the incremental diagnostic value of CMR, we have compiled the largest series of apical pouches detected using CMR. Further, this is the largest series of apical pouches irrespective of imaging technique. We have shown CMR is superior to echocardiography in detecting apical pouches, especially with smaller pouch dimension. The use of intravenous contrast aids in the detection of apical pouches using echocardiography. Nonetheless, even with contrast more than half of the apical pouches in our series were not detected on echocardiography. These findings have important implications when considering the role of apical pouches in risk stratification of patients with HCM. Our findings suggest that there may be an increased probability of missing apical pouches in contemporary echocardiographic studies, and in this setting, the evaluation of clinical risk of SCD may be untowardly influenced by the limitations of the imaging technique.
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Moreover, the current study has demonstrated that apical pouches, although usually considered a complication of apical subtype HCM, may also be associated with other morphologic subtypes (reversed curve, sigmoid, neutral), as noted in 26.8 % of our series.
Limitations Some limitations of this study warrant discussion. First, there has been a spectrum of apical abnormalities described starting from apical hypokinesis, leading to outpouching, with an end result of an aneurysm formation [13]. In our study, apical outpouching and apical aneurysms were not analyzed as separate entities, but were collectively referred to as apical pouches. Patients with angiographically proven CAD that could contribute to a different mechanism of apical pouch formation were included. Second, although a retrospective study design may be regarded as a limitation of the study, our primary goal of defining anatomic findings of apical pouches using CMR and comparing all CMR examinations with echocardiographic findings should not be negatively influenced by a retrospective study design. Third, our study was not primarily designed to evaluate clinical outcomes; however, our findings do influence future study of the spectrum of disease under the umbrella of HCM. Given the main finding of CMR being superior to echocardiography in the assessment of apical cardiac structures future study of HCM and clinical risk stratification, would indicate that in addition to LGE findings, CMR would play a greater role with regard to anatomic substrate for risk of SCD. While we did not assess if there are any patients in whom apical pouches were detected on echocardiography and missed on CMR, we believe this is less likely as CMR found apical pouches in a substantial proportion where echocardiography had missed the diagnosis. Additionally, the primary aim of this study was to study the anatomic variation of apical pouches using CMR in this the largest study of its kind. Secondarily, we were able to compare differences between CMR and echocardiographic findings.
Conclusion Patients with apical pouches represent an important, underdiagnosed subset of HCM patients. Apical pouches are most common in apical HCM, but can be found in other phenotypic variants. While the use of IV contrast aids in the detection of apical pouches using echocardiography, CMR is better suited for the evaluation of apical pouches in HCM. If clinical suspicion is high, even in the absence of an apical pouch on echocardiography, CMR should be used
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because timely identification of apical pouches can significantly impact management and outcomes.
Conflict of interest
None.
References 1. Klues HG, Schiffers A, Maron BJ (1995) Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol 26(7):1699–1708 2. Binder J et al (2006) Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations. Mayo Clinic Proc 81(4):459–467 3. Maron MS et al (2008) Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation 118(15):1541–1549 4. Ando H et al (1990) Apical segmental dysfunction in hypertrophic cardiomyopathy: subgroup with unique clinical features. J Am Coll Cardiol 16(7):1579–1588 5. Wigle ED, Rakowski H (1992) Hypertrophic cardiomyopathy: when do you diagnose midventricular obstruction versus apical cavity obliteration with a small nonobliterated area at the apex of the left ventricle? J Am Coll Cardiol 19(3):525–526 6. Nakamura T et al (1992) Diastolic paradoxic jet flow in patients with hypertrophic cardiomyopathy: evidence of concealed apical asynergy with cavity obliteration. J Am Coll Cardiol 19(3):516–524 7. Fighali S et al (1987) Progression of hypertrophic cardiomyopathy into a hypokinetic left ventricle: higher incidence in patients with midventricular obstruction. J Am Coll Cardiol 9(2):288–294 8. Matsubara K et al (2003) Sustained cavity obliteration and apical aneurysm formation in apical hypertrophic cardiomyopathy. J Am Coll Cardiol 42(2):288–295
9. Sanghvi NK, Tracy CM (2007) Sustained ventricular tachycardia in apical hypertrophic cardiomyopathy, midcavitary obstruction, and apical aneurysm. Pacing Clin Electrophysiol PACE 30(6):799–803 10. Tse HF, Ho HH (2003) Sudden cardiac death caused by hypertrophic cardiomyopathy associated with midventricular obstruction and apical aneurysm. Heart 89(2):178 11. Lazaros G et al (2007) Apical hypertrophic cardiomyopathy with midventricular obstruction and apical aneurysm. Int J Cardiol 114(2):E45–E47 12. Gersh BJ et al (2011) ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 124(24):2761–2796 13. Binder J et al (2011) Apical hypertrophic cardiomyopathy: prevalence and correlates of apical outpouching. J Am Soc Echocardiogr 24(7):775–781 14. Moon JC et al (2004) Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart 90(6):645–649 15. Rickers C et al (2005) Utility of cardiac magnetic resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circulation 112(6):855–861 16. Maron MS, Lesser JR, Maron BJ (2010) Management implications of massive left ventricular hypertrophy in hypertrophic cardiomyopathy significantly underestimated by echocardiography but identified by cardiovascular magnetic resonance. Am J Cardiol 105(12):1842–1843 17. Kim KH et al (2012) Myocardial scarring on cardiovascular magnetic resonance in asymptomatic or minimally symptomatic patients with ‘‘pure’’ apical hypertrophic cardiomyopathy. J cardiovasc Magn Reson 14:52 18. Fattori R et al (2010) Significance of magnetic resonance imaging in apical hypertrophic cardiomyopathy. Am J Cardiol 105(11):1592–1596 19. McKenna W et al (1981) Prognosis in hypertrophic cardiomyopathy: role of age and clinical, electrocardiographic and hemodynamic features. Am J Cardiol 47(3):532–538 20. Elliott P et al (2006) Left ventricular outflow tract obstruction and sudden death in hypertrophic cardiomyopathy. Eur Heart J 27(24):3073 author reply 3073-4
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ORIGINAL PAPER
Evaluation of apical pouches in hypertrophic cardiomyopathy using cardiac MRI Kalie Y. Kebed • Raed I. Al Adham • Kalkidan Bishu • J. Wells Askew • Kyle W. Klarich • Jae K. Oh • Paul R. Julsrud • Thomas A. Foley • James F. Glockner • Rick A. Nishimura • Steve R. Ommen • Nandan S. Anavekar
Received: 7 October 2013 / Accepted: 23 December 2013 Ó Springer Science+Business Media Dordrecht 2014
Abstract The presence of apical pouches in hypertrophic cardiomyopathy (HCM) may portend poor prognosis. We sought to study if the use cardiac magnetic resonance imaging (CMR) improves the detection of apical pouches in HCM compared to echocardiography. A retrospective review was performed of all consecutive HCM patients with an apical pouch identified by CMR at Mayo Clinic from May 2004 to Sept 2011. Clinical data was abstracted and CMR and echocardiographic images were analyzed. There were 56 consecutive HCM patients with an apical pouch identified by CMR. The predominant morphological type was apical in 41 (73.2 %), followed by sigmoid in 6 (10.7 %), reversed curve in 6 (10.7 %) and neutral in 3 (5.4 %). Obstructive physiology or systolic anterior motion of the mitral valve leaflet was evident in 23 (41.1 %). Late gadolinium enhancement was present in 47 (87.0 %) patients. Apical pouches were detected in only 18 (32.1 %) patients on echocardiography. Even when intravenous contrast was used (29/56 patients), in 16/29 (55.2 %)
K. Y. Kebed (&) Department of Internal Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA e-mail: [email protected] R. I. Al Adham Department of Internal Medicine, St. Joseph’s Hospital, Phoenix, AZ, USA K. Bishu J. W. Askew K. W. Klarich J. K. Oh R. A. Nishimura S. R. Ommen N. S. Anavekar Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA P. R. Julsrud T. A. Foley J. F. Glockner Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
pouches were missed on echocardiography. Pouch length and neck dimensions in systole and diastole, measured on CMR, were larger among those patients in whom pouches were detected on echocardiography suggesting only larger pouches can be identified on echocardiography. In the largest CMR series to date of apical pouches in HCM, we show that while apical pouches are most commonly seen in apical HCM, they can be found in other phenotypic variants. CMR is better suited for the evaluation of apical pouches compared to echocardiography even with the use of intravenous contrast. CMR is likely a better tool for evaluating the cardiac apical structures including apical pouches when clinically indicated. Keywords Apical pouches Hypertrophic cardiomyopathy Cardiac MRI Echocardiography Abbreviations HCM Hypertrophic cardiomyopathy LV Left ventricle SCD Sudden cardiac death ICD Implantable cardioverter-defibrillator CMR Cardiac magnetic resonance NSVT Non-sustained ventricular tachycardia LVOT Left ventricular outflow tract SAM Systolic anterior motion SSFP Steady state free precession LGE Late gadolinium enhancement
Background Hypertrophic cardiomyopathy (HCM), a relatively common genetic cardiovascular disease, is characterized by a hypertrophied, non-dilated left ventricle (LV) in the absence of
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other diseases capable of explaining the extent of hypertrophy. HCM is phenotypically classified into four morphological subtypes (apical, sigmoid, reversed curve, and neutral) [1, 2]. Within the diverse phenotypic spectrum of HCM, a subset of patients with apical pouches has been described, with a reported prevalence of 2 % [3]. Proposed mechanisms for the development of apical pouches have included LV wall stress secondary to mid-cavitary obstruction and genetic predisposition [4–8]. Earlier studies have suggested a poor prognosis in patients with apical pouches [3, 9–11]. Maron et al. [3] reported a combined adverse event [sudden cardiac death (SCD), appropriate implantable cardioverter-defibrillator (ICD) discharges, nonfatal thromboembolic stroke, progressive heart failure and death] rate of 10.5 % per year in HCM patients with apical pouches. The presence of an apical pouch has thus been identified as an SCD risk modifier in the latest HCM guidelines [12]. More data is needed to determine the best way to diagnose apical pouch so that further clinical assessments regarding the benefits of anticoagulation and surgical resection can be assessed more accurately. Given the prognostic implications, accurate identification of apical pouches is important for counseling patients on the expected risks and future investigations regarding the clinical implication of apical pouches. We aim to characterize cardiac magnetic resonance (CMR) findings of apical pouches in HCM and determine the incremental diagnostic value of CMR.
Methods Patient selection This was a retrospective review of 56 consecutive HCM patients with an apical pouch identified by CMR at Mayo Clinic from May 2004 to Sept 2011. Apical pouches were defined as an area of wall thinning and dyskinesis involving the LV apex. CMR and echocardiographic images were analyzed to determine pouch size and incremental diagnostic value of CMR. The study was approved by the Mayo Clinic Institutional Review Board. Clinical data Clinical and demographic data from the electronic medical records at the time of CMR study was abstracted. This included age, gender, ethnicity, genotype, and structural subtype. Co-morbidities included hypertension; diabetes mellitus; coronary artery disease, defined by either angiographically (invasive or CT) proven 50 % stenosis or prior myocardial infarction; history of atrial fibrillation; and history of syncope. First-degree family history of HCM
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and SCD were recorded. Presence of severe symptoms was defined as the presence of either New York Heart Association class C3 dyspnea or Canadian Cardiovascular Society angina class C3. ECG and Holter monitoring Additional data was abstracted in patients with ECG and Holter monitoring within 6 months of CMR. ECGs were examined for PR, QRS and QT interval duration, ST segment and T wave changes, presence of bundle branch block and atrial fibrillation. Holter reports were examined for the presence of total ventricular beats, ventricular couplets or bigeminy, and number of non-sustained ventricular tachycardia episodes (NSVT) defined as 3 or more consecutive ventricular beats. Echocardiography Two-dimensional echocardiograms performed within 6 months of the CMR study were reviewed in each patient. Magnitude and distribution of LV hypertrophy, intracavitary and LV outflow tract (LVOT) velocities, strain rate analysis, and presence or absence of apical pouches and thrombus were recorded. A single reviewer (K.B.), blinded to clinical and CMR data, reviewed the echocardiograms. Cardiac MRI Cardiac magnetic resonance studies were reviewed for magnitude and distribution of LV hypertrophy, apical pouch, thrombus, LVOT obstruction, systolic anterior motion (SAM) of the mitral valve, and late gadolinium enhancement (LGE) presence and distribution. Apical pouch anatomy and dimensions; LV ejection fraction, LV end-systolic and end-diastolic diameters and volumes, LV end-diastolic mass, and maximal (end diastolic) septal thickness were analyzed using steady state free precession (SSFP) sequences in multiple imaging planes. The product delayed enhancement sequence that was used to assessment of myocardial viability is a conventional 2D inversion recovery gradient echo pulse sequence. A double dose of gadolinium (0.2 mol/kg) was infused, and LGE imaging occurred at approximately 10 min after the administration of contrast. Apical pouch anatomy was best demonstrated in long axis views including the two, three and four chamber views. Volumetric and mass data were recorded from the short-axis imaging plane. A single reviewer (N.A.), blinded to clinical and echocardiography data, reviewed the CMR studies and measured the apical pouch dimensions. Pouch measurements were made on the Advantage Workstation. A single reviewer (N.A.) performed the MRI
Int J Cardiovasc Imaging Table 1 Clinical features of the study patients Variables
Table 2 Electrocardiographic finding of the study patients
Value
n
Demographics Age, years
57.5 ± 16.5
Atrial Fibrillation (ECG) n (%)
4 (7)
56
Atrial Fibrillation (History) n (%)
13 (23)
56
PR interval (ms)
172 ± 29
52 56
31 (55.4)
56
Ethnicity, white n (%)
42 (85.7)
49
Risk factors and comorbidities Diabetes mellitus (%) Coronary artery disease, angiographic (%) Prior myocardial infarction
n
56
Gender, male n (%)
Hypertension n (%)
Apical pouches
QRS interval (ms)
105 ± 26
QTc interval (ms)
450 ± 65
56
Axis, degree
24 ± 33
56
26 (46.4)
56
3 (5.4)
56
ST depression C 1 mm n (%)
15 (27)
56
56
T-wave inversion C 5 mm n (%)
33 (59)
56
56
T-wave inversion C 10 mm n (%)
9 (16)
56
14 (25) 7 (12.5)
Atrial fibrillation (%)
13 (23.2)
56
Positive T-wave C 10 mm n (%)
2 (4)
56
Syncope (%) Severe symptoms (%)
4 (7.1) 23 (41.1)
56 56
Abnormal Q-wave n (%) RBBB n (%)
0 (0) 1 (2)
56 56
LBBB n (%)
6 (11)
56
First degree relative with HCM (%)
8 (14.3)
56
Sudden cardiac death in first degree relative (%)
1 (1.8)
56
Results measurements twice per study. The pouches were identified on the clinical report. The long dimension was from the tip of the pouch to the neck and the transverse dimension across the neck of the pouch at systole and diastole. Reproducibility of the measurement was not performed but the measurements were systematically larger than that recorded on echocardiography by a blinded second reviewer (K.B.). The difference between two different modalities was the goal of the measurements since the size of the apical pouches is not routinely reported on the clinical reports. For this reason, our group did not think that it was necessary to perform procedures to test the reproducibility of the measurement. LGE enhancement was taken from the clinical report and did not use any automated software to ascribe a threshold for enhancement. All studies were performed on a 1.5-Tesla MRI scanner (Signa Twin Speed Excite, General Electric, Waukesha, Wis).
Clinical and demographic features
Statistical analysis
Electrocardiography and holter monitoring
Mean ± standard deviation or number (frequency) are presented to summarize data for continuous and nominal variables, respectively. Pouch length and neck dimensions in systole and diastole were compared using independent, two-sample t tests. Pearson’s Chi square test was used to compare the proportion of use of intravenous contrast among patients in whom pouches were diagnosed and missed on echocardiography. Fisher’s exact test was used to compare the proportion of patients with LGE on CMR and detection of a pouch on echocardiography as 2 cells had expected counts [5. p \ 0.05 was considered statistically significant. Analysis was performed using IBM SPSS Statistics software Version 19 (Armonk, NY).
ECGs at the time of the CMR were available in all patients, and the results are summarized in Table 2. Mean PR, QRS, and QTc intervals were 172 ± 29, 105 ± 26 and 450 ± 65 ms, respectively. Of the 13 (23 %) patients with a history of atrial fibrillation, 4 (7 %) were in atrial fibrillation at the time of ECG study. ST depression was present in 15 (27 %). T wave inversions C5 and C10 mm were seen in 33 (59 %) and 9 (16 %), respectively. None had abnormal Q waves. Right bundle branch block was present in 1 (2 %). Left bundle branch block was present in 6 (11 %). A 24-hour Holter ECG was performed in 42 patients. Of these, 11 (26.2 %) had C1 run of NSVT. Mean total
There were 817 consecutive patients evaluated at our center with echo and CMR with a diagnosis of HCM at the Mayo Clinic (Rochester, MN) from May 2004 to Sept 2011. Of these, there were 56 (6.9 %) patients with an apical pouch identified by CMR. Demographics and comorbidities are summarized in Table 1. Mean age was 57.5 ± 16.5 years, 31 (55.4 %) were male, and 42 (85.7 %) were Caucasian. Comorbidities included hypertension in 26 (46.4 %), diabetes mellitus in 3 (5.4 %) and atrial fibrillation in 13 (23.2 %) patients. Coronary artery disease was present in 14 (25.0 %), and 7 (12.5 %) patients had a prior myocardial infarction. A history of syncope was reported in 4 (7.1 %) while 23 (41.1 %) patients had severe symptoms. There was known family history of HCM in 8 (14.3 %), and 1 (1.8 %) has SCD in a first degree relative.
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Int J Cardiovasc Imaging Table 3 Echocardiography findings of the study patients Variables
Value
Available
Septal thickness (mm)
15.5 ± 4.8
54
Posterior wall thickness (mm)
13.1 ± 3.2
53
Ejection fraction (%)
69.3 ± 7.0
55
LVOT velocity resting (m/s)
1.9 ± 1.4
42
Basal Strain average (%)
-7.2 ± 15.5
24
Mid Strain average (%)
-4.3 ± 11.9
25
Apical Strain average (%)
-4.8 ± 7.9
18
Average LV strain (%)
-7.7 ± 7.4
16
Apical pouch (%)
18 (32)
56
Apical thrombus (%)
1 (2.2)
46
Table 4 CMR findings of the study patients Variables
Value
n
LV EF (%)
67.1 ± 9.9
56
LV end diastolic volume (ml)
131.7 ± 34.6
55
LV end systolic volume (ml)
44.1 ± 19.5
55
Maximal thickness (mm)
21.5 ± 4.5
44
Apical pouch length in diastole (mm)
15.7 ± 7.5
56
Apical pouch neck in diastole (mm)
17.0 ± 8.4
56
Apical pouch length in systole (mm)
18.2 ± 10.8
56
Apical pouch neck in systole (mm)
17.2 ± 10.4
56
Obstructive physiology or SAM (%)
23 (41)
56
Systolic anterior motion of mitral valve leaflets (%)
19 (34)
56
Late gadolinium enhancement (LGE) n (%)
47 (87)
54
Apical pouch n (%)
56 (100)
56
Apical Thrombus n (%)
2 (3.6)
56
ventricular beats was 402 ± 1682 and ventricular couplets or bigeminy was 9.3 ± 45.9.
Fig. 1 Compares the pouch dimensions measured on CMR between those patients with prior diagnosis of apical pouch on echocardiography (black bars) and those with apical pouches only diagnosed on CMR (white bars). The dimension standard deviations are represented by the thin ‘‘T’’ lines. The y-axis is length measured in millimeters. Compared using independent, two-sample t tests. p \ 0.05 comparing dimensions measured on CMR between patients in which pouch was and was not seen on echo
Cardiac MRI The CMR findings are summarized in Table 4. On CMR, the predominant morphological type was apical in 41 (73.2 %), followed by sigmoid in 6 (10.7 %), reversed curve in 6 (10.7 %) and neutral in 3 (5.4 %). LV ejection fraction was 67 ± 10 %, range 45.0–79.0 %. LV end-diastolic and end-systolic volumes were 131.7 ± 34.6 and 44.1 ± 19.5 ml, respectively. Maximum LV thickness was 21.5 ± 4.5 mm. Obstructive physiology or SAM was evident in 23 (41.1 %) patients. LGE was present in 47 (83.9 %) patients. Of those 47, the distribution involved the apex in 28 (77.8 %) patients. The mean pouch length was 15.7 ± 7.5 and 18.2 ± 10.8 mm in diastole and systole, respectively. The mean pouch neck was 17.0 ± 8.4 and 17.2 ± 10.4 mm in diastole and systole, respectively. Thrombus was present in 2 (3.6 %) of pouches. The diagnostic value of echocardiography and CMR
Echocardiography All 56 patients had an echocardiogram performed within 6 months of the CMR study. Intravenous contrast (Definity or Optison) was used in 29 (52 %) patients. The echocardiography findings are summarized in Table 3. Apical pouches were detected in 18 (32.1 %) patients. Of the 18 apical pouches detected, 13 examinations utilized intravenous contrast agent. The pouch length was 20.2 ± 6.4 and 18.1 ± 5.9 mm in diastole and systole, respectively. The pouch neck was 13.0 ± 4.3 and 10.2 ± 3.6 mm in diastole and systole, respectively. Echocardiography detected thrombus in 1 apical pouch.
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All the pouches seen on echocardiography were also demonstrated on CMR. Patients in whom pouches were detected on echocardiography had larger measured pouch dimensions on CMR. The pouch length in diastole was 18.3 ± 6.0 and 14.4 ± 7.9 mm in those seen on echocardiography versus those that were missed, respectively (p \ 0.05). Likewise, the pouch length in systole was 24.9 ± 8.0 and 15.5 ± 10.9 mm, respectively (p \ 0.05). The pouch neck in diastole was 20.8 ± 7.6 and 15.1 ± 8.2 mm, respectively (p \ 0.05). The pouch neck in systole was 23.3 ± 8.0 and 14.4 ± 10.2 mm, respectively (p \ 0.05). These findings are summarized in Fig. 1. Intravenous contrast was
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Discussion
Fig. 2 CMR steady state free precession four chamber view demonstrating apical HCM with an apical pouch
Fig. 3 Echo 2D apical long axis view without contrast enhancement demonstrating abnormal LV wall thickness
used in 13 of 18 (72.2 %) patients who had pouches detected on echocardiography while 16 of 38 (42.1 %) of patients in whom pouches were missed on echocardiography had used intravenous contrast (p = 0.16). Of the 29 patients receiving contrast, 16 (55.2 %) of pouches were not detected on echocardiography. Figure 2 is a CMR SSFP four chamber view demonstrating apical HCM with an apical pouch that was not seen on Fig. 3, the corresponding echo 2D apical long axis view. The finding of LGE was not associated with identification of apical pouch on echo. 2 (11 %) of those with pouches found on echo had LGE whereas 5 (14 %) of those with pouches not detected on echo had LGE (p = 0.6).
This study is the largest series of apical pouches in the current literature demonstrating, primarily anatomic features of apical pouches, and secondarily differences in their identification comparing CMR and echocardiographic imaging modalities. We have demonstrated a much higher prevalence of apical pouches (6.9 %) than previously reported in predominately echocardiographic studies. In a large study reporting a prevalence of 2.2 %, only 22 of 1299 patients were evaluated with CMR [3]. Similarly, in a purely echocardiography study, true apical pouches were seen in 6 of 193 patients (3.1 %) [13]. Our higher prevalence is a reflection of the superiority of CMR in detecting apical pouches. Given the clinical implications of apical pouches, specifically their relation to SCD and the role of adjunctive medical therapies, this study provides novel insight regarding imaging evaluation. The main findings of this study suggest that CMR is superior to echocardiography in the identification and qualification of apical cardiac structures, even after accounting for echocardiographic techniques used to enhance endocardial border definition. The genotypic and phenotypic expression in HCM is wide, and there is an underappreciated subset with thin walled apical pouches seen typically in apical HCM. Echocardiography is the standard imaging modality in HCM, although, CMR is emerging as a valuable adjunct that is primarily used to assess for LGE but may have an equally important role in detecting apical pouches. CMR is recommended in patients with known HCM when additional information may have an impact on management [14–16]. Some authors have suggested that CMR provides more accurate information on LV morphology [14] and is superior in detecting apical pouches. In recent studies, nearly one in two apical pouches seen on CMR were undetected by prior echocardiography [3, 17, 18]. In 2008, Maron et al. [3] identified 28 HCM patients with apical pouches using CMR, 12 (43 %) of which were undetected by echocardiography. In 2010, Fattori et al. [18] studied 13 apical HCM patients, 9 with prior echocardiographic diagnosis of apical HCM and 4 with normal or inconclusive results. Apical pouch was identified in 4 (31 %) patients on CMR, three (75 %) of which were not seen on prior echocardiography. In 2012, Kim et al. [17] published a report of 40 apical HCM patients and discovered 5 (12.5 %) with apical pouches on CMR, 3 (60 %) of which were not seen on routine echocardiography. A poor prognosis with SCD in patients with apical pouches has been reported [3, 9–11], although, more recent studies suggest a more favorable prognosis [13, 17]. In the aforementioned study published by Maron et al. 12
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(43 %) apical pouch patients experienced adverse disease complications with a combined adverse event rate of 10.5 % per year. Greater than 40 % of patients with SCD or appropriate ICD discharges had 0 of the 5 conventional primary prevention risk factors, suggesting apical pouch formation might be a novel, independent risk factor. This led to the updated guidelines recognizing apical pouches as potential SCD risk modifier [3, 12]. In the 5 apical pouch patients reported by Kim et al. [17] at 2 year follow-up, no patient had the composite endpoint of SCD, all-cause mortality, or hospitalization for heart failure. Binder et al. [13] studied 193 apical HCM patients, of which 29 patients had a spectrum of apical outpouching identified on echocardiography. Overall mortality, SCD, and ICD discharge events were not more common in patients with apical outpouching. Although the recent prognostic data initially appears conflicting, the methodologies of the studies have key differences that need to be accounted for. Kim et al. had a very small sample size (n = 5) and a short 2 year follow-up period preventing definitive conclusions regarding prognosis. Maron et al. followed the clinical course of all identified apical pouch patients regardless of morphology, whereas the Binder et al. analysis compared apical HCM patients with and without pouches and excluded those with LVOT obstruction, an accepted SCD risk modifier [12, 19, 20]. The literature in its entirety is based on small sample sizes, and more data is needed to clarify the prognosis. Further, there is a paucity of data on the therapeutic implications of apical pouches, and there is no consensus on the role of anticoagulation and prophylactic surgical resection, which is currently managed on a case-by-case basis. Given the potential prognostic implications, identification of apical pouches is important for counseling and management of HCM patients. To characterize the findings of apical pouches and determine the incremental diagnostic value of CMR, we have compiled the largest series of apical pouches detected using CMR. Further, this is the largest series of apical pouches irrespective of imaging technique. We have shown CMR is superior to echocardiography in detecting apical pouches, especially with smaller pouch dimension. The use of intravenous contrast aids in the detection of apical pouches using echocardiography. Nonetheless, even with contrast more than half of the apical pouches in our series were not detected on echocardiography. These findings have important implications when considering the role of apical pouches in risk stratification of patients with HCM. Our findings suggest that there may be an increased probability of missing apical pouches in contemporary echocardiographic studies, and in this setting, the evaluation of clinical risk of SCD may be untowardly influenced by the limitations of the imaging technique.
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Moreover, the current study has demonstrated that apical pouches, although usually considered a complication of apical subtype HCM, may also be associated with other morphologic subtypes (reversed curve, sigmoid, neutral), as noted in 26.8 % of our series.
Limitations Some limitations of this study warrant discussion. First, there has been a spectrum of apical abnormalities described starting from apical hypokinesis, leading to outpouching, with an end result of an aneurysm formation [13]. In our study, apical outpouching and apical aneurysms were not analyzed as separate entities, but were collectively referred to as apical pouches. Patients with angiographically proven CAD that could contribute to a different mechanism of apical pouch formation were included. Second, although a retrospective study design may be regarded as a limitation of the study, our primary goal of defining anatomic findings of apical pouches using CMR and comparing all CMR examinations with echocardiographic findings should not be negatively influenced by a retrospective study design. Third, our study was not primarily designed to evaluate clinical outcomes; however, our findings do influence future study of the spectrum of disease under the umbrella of HCM. Given the main finding of CMR being superior to echocardiography in the assessment of apical cardiac structures future study of HCM and clinical risk stratification, would indicate that in addition to LGE findings, CMR would play a greater role with regard to anatomic substrate for risk of SCD. While we did not assess if there are any patients in whom apical pouches were detected on echocardiography and missed on CMR, we believe this is less likely as CMR found apical pouches in a substantial proportion where echocardiography had missed the diagnosis. Additionally, the primary aim of this study was to study the anatomic variation of apical pouches using CMR in this the largest study of its kind. Secondarily, we were able to compare differences between CMR and echocardiographic findings.
Conclusion Patients with apical pouches represent an important, underdiagnosed subset of HCM patients. Apical pouches are most common in apical HCM, but can be found in other phenotypic variants. While the use of IV contrast aids in the detection of apical pouches using echocardiography, CMR is better suited for the evaluation of apical pouches in HCM. If clinical suspicion is high, even in the absence of an apical pouch on echocardiography, CMR should be used
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because timely identification of apical pouches can significantly impact management and outcomes.
Conflict of interest
None.
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