Surgical pathology of subaortic septal myectomy

Cardiovascular Pathology 33 (2018) 32–38

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Cardiovascular Pathology

Original Article

Surgical pathology of subaortic septal myectomy: histology skips over clinical diagnosis☆,☆☆ João Abecasis a,b,⁎, Rosa Gouveia c,d,e, Mariana Castro a, Maria João Andrade a, Regina Ribeiras a, Sância Ramos c, Miguel Abecasis f, Nuno Cardim b,g, Victor Gil h,i a

Cardiology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental Carnaxide, Portugal Nova Medical School, Lisboa, Portugal Pathology Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental Carnaxide, Portugal d Faculty of Medicine, University of Coimbra, Coimbra, Portugal e Forensic Pathology, Instituto Nacional de Medicina Legal e Ciências Forenses, Coimbra, Portugal f Cardiothoracic Surgery Department, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental Carnaxide, Portugal g Cardiology Department, Hospital da Luz, Lisboa h Cardiology Department, Hospital dos Lusíadas, Lisboa i Faculdade de Medicina, Universidade de Lisboa b c

a r t i c l e

i n f o

Article history: Received 2 December 2017 Received in revised form 17 December 2017 Accepted 20 December 2017 Available online xxxx Keywords: Hypertrophic cardiomyopathy Septal myectomy Reactive myocardial hypertrophy Histomorphology

a b s t r a c t Background: Subaortic septal myectomy is usually performed to mitigate obstruction in patients with the obstructive form of hypertrophic cardiomyopathy (HCM) or in those with congenital subaortic stenosis. Moreover, it is combined with aortic valve replacement in patients with severe aortic valve stenosis (SAS) and asymmetrical septal hypertrophy causing concomitant left ventricular outflow tract obstruction. When both conditions coexist, it is conceptually difficult to identify a cardiomyopathy beyond an adaptive myocardial hypertrophy, strictly related to pressure overload. Myectomy histopathology might be useful to enlighten the cause of the obstruction and establish the diagnosis. Aim: The aim was to describe the pathological findings of surgical septal myectomy specimens obtained from a group of patients with diverse clinical diagnosis, including HCM, severe aortic stenosis, and asymmetrical septal hypertrophy. Methods: This was a retrospective study of 56 patients undergoing septal myectomy along a 10-year period at a tertiary cardiac surgical center. Clinical, interventional, and anatomopathological findings between patients with and without a preoperative diagnosis of HCM were analyzed and compared. Results: Mean age at intervention was 67.5±20.5 years; 37 (66.1%) were female Preoperative diagnosis of sarcomeric obstructive HCM was assumed in 23 (41.1%) patients. All the other patients (58.9%) were referred for surgery with preoperative diagnosis of asymmetric septal hypertrophy, mainly in the context of severe aortic stenosis (24 patients). Twenty-seven (48.2%) patients had a greater than 30 mmHg intraventricular gradient at rest. Patients with presumed HCM were significantly younger (56.5±15.8 vs. 70.2±13.3 years, Pb.001), had higher prevalence of significant intraventricular obstruction at rest [20 (87.0%) vs. 8 (34.8%), Pb.001], and more frequently had moderate or severe mitral regurgitation [9 (39.1%) vs. 5(15.1%), P=.043]. All patients with aortic valve stenosis underwent both aortic valve replacement and septal myectomy. Twelve (52.1%) of the patients with obstructive HCM had isolated septal myectomy, while in the remaining 11, the procedure was combined with intervention on the mitral valve. Histopathological final diagnosis was of nonspecific reactive myocardial hypertrophy in all but 4 (92.2%) patients. In those, 2 (3.6%) had the final diagnosis of HCM and 2 (3.6%) the diagnosis of congenital subaortic membranous stenosis with reactive myocardial hypertrophy. Different grades of subendocardial fibroelastosis and myocardial fibrosis, mainly interstitial, were present [27 (48.2%) and 18 (32%) patients, respectively]. When microscopic data were compared between patients with or without a preoperative clinical diagnosis of HCM, no significant differences were found.

☆ Funding: not applicable. ☆☆ Conflicts of interest: There are no conflicts of interest. ⁎ Corresponding author at: Avenida Professor Reynaldo dos Santos, 2790-134 Carnaxide, Lisboa. Tel.: +351 914054977; fax: +351 214241388. E-mail address: [email protected] (J. Abecasis).

https://doi.org/10.1016/j.carpath.2017.12.002 1054-8807/© 2017 Elsevier Inc. All rights reserved.

J. Abecasis et al. / Cardiovascular Pathology 33 (2018) 32–38

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Conclusion: In patients submitted to surgical septal myectomy, histology was mostly indistinctive among different clinical entities. Since different myocardial hypertrophy etiologies may share similar pathological expression, there is a need for detailed clinical assessment when trying to define the best strategy for clinical management. © 2017 Elsevier Inc. All rights reserved.

1. Introduction Left ventricular septal myectomy is carried out to reduce outflow tract obstruction in patients with either hypertrophic cardiomyopathy (HCM) or the less common forms of congenital subaortic stenosis [1]. Currently, it is increasingly performed in patients with severe aortic stenosis, of which asymmetrical septal hypertrophy may be present in up to 10% [2]. However, pathophysiology behind both conditions is not clearly established, and in most subjects, clinical and imaging evaluations fail to clarify if obstructive septal hypertrophy is merely a consequence of valvular disease imposed afterload. Moreover, the presence of both conditions creates some difficulties when trying to assign predominant hemodynamic contribution to one or the other [3,4]. As a practical consequence, it is still poorly defined when to perform myectomy in patients who are proposed to undergo aortic valve replacement [2,5]. In elderly populations, isolated basal septal hypertrophy, often defined as ≥15-mm septal wall thickness without any other segment involvement, may also result in symptomatic left ventricular outflow tract obstruction. Usually, this clinical entity affects older women with no previous history of familial cardiomyopathy. It has less frequently associated electrocardiographic (ECG) abnormalities suggesting HCM and does not exhibit common HCM echocardiographic features such as papillary muscle abnormalities, several segments’ involvement, or hypertrabeculation, being strictly confined to a hypertrophied, often angulated, basal septum [6,7]. However, application of current HCM definition criteria in these cases would result in HCM diagnosis. In this way, histology might be helpful to differentiate these apparently different clinical cases. Despite being attractive for both diagnostic and management purposes, analysis of microscopic abnormalities of septal myectomy specimens is often nonspecific [8]. Definitive sarcomeric HCM diagnosis obtained from histology is not always recognized in patients with asymmetric septal hypertrophy even when concomitant aortic valve stenosis is absent [9]. In addition, pathology data from septal myectomy specimens in different clinical contexts are scarce. Thus, the purpose of our study is (1) to describe the pathology findings of surgical septal myectomy specimens obtained from a broad and heterogeneous population, which includes not only patients with the presumed diagnosis of HCM but also patients with either isolated septal hypertrophy or septal hypertrophy associated with aortic valve stenosis, and (2) to analyze the microscopic findings taking into account clinical data and interventional procedures, comparing the groups with and without preintervention diagnosis of HCM. 2. Material and methods

procedure and septal myectomy, surgeons’ appraisal of the septum, and complications in close relation to surgery. At our institution, for diagnostic and routine purposes, anatomopathological evaluation is performed in every single cardiac tissue sample. Our surgical informed consent form includes a statement asking permission for patient samples` analysis and eventual anonymized data publication. 2.2. Pathology Data were obtained from surgical specimen’s pathology report, regarding both macroscopic and histological findings, as well as final pathology diagnosis. Microscopic slides were reviewed, and for the purpose of our study, this was performed without knowing the patients’ clinical history and the referral reason for surgery (blind review). The specimens had been fixed in 10% buffered formalin, embedded in paraffin, and stained with hematoxylin–eosin. Additional Masson’s Trichrome stain was used for collagen/fibrosis assessment and elastic van Gieson’s for normal or pathologic elastic fibers. All samples were specifically evaluated in order to confirm or exclude the presence of endocardial/subendocardial fibrotic/fibroelastic thickening, myocyte hypertrophy, myocardial fibrosis, disarray, vascular abnormalities, abnormal substance deposition, or any other lesion. For diagnostic purposes, hypertrophy was diagnosed if myocyte diameters were greater than 20 μm with consistent enlarged and hyperchromatic nuclei. Interstitial fibrosis was defined as increased fibrous tissue in the myocardium interstitium separating myocardial fibers. Replacement fibrosis corresponded to areas of dense fibrous tissue filling foci/areas of myocardial fibers loss [10]. Both were confirmed using histochemical stains (Masson’s Trichrome and elastic van Gieson). Elastic van Gieson also allowed the observation of normal and increased elastic fibers. Cellular interlacing, whirling, or herringbone patterns defined disarray. The definition of sarcomeric HCM relied on the presence of myocyte hypertrophy, disarray, interstitial fibrosis, small vessel abnormalities (thick-walled intramural arteries with medial hypertrophy, intimal hyperplasia, and vascular dysplasia), and subendocardial fibroelastosis [11]. 2.3. Statistical analysis The whole analysis was performed using SPSS (version 21.0; SPSS, Chicago, IL, USA). Data are expressed as mean±S.D., unless otherwise indicated. Discrete variables are given in frequency and percentage. For comparisons, a P value b.05 was considered significant. All P values are two tailed. Comparison of continuous variables were made using the unpaired Student’s t test or Mann–Whitney test for nonnormally distributed data, and for comparison of categorical data, the χ2 test. Our hospital institutional review board approved this retrospective study.

2.1. Group of patients: clinical data 3. Results We performed a retrospective analysis from consecutive patients submitted to septal myectomy in a tertiary Cardiology and Cardiac Surgery Center between January 2006 and December 2016. All patients who underwent this procedure were included. Clinical data from 56 patients were collected regarding gender, age at diagnosis, previous history of systemic hypertension or other cardiac surgery, clinical presentation, ECG findings, echocardiographic data as assessed by basal septal thickness, presence of significant intraventricular gradient and mitral valve disease, presumptive preoperative clinical diagnosis, type of surgical

3.1. Clinical data For the whole group of 56 patients submitted to septal myectomy, mean age was 67.5±20.5 years and 37 (66.1%) were female. Preoperative diagnosis of sarcomeric obstructive HCM was assumed in 23 (41.1%) patients based on familial, clinical, and echocardiographic findings [7 (12.5%) patients with documented familial diagnosis], and 2 of these patients had also aortic valve stenosis. In patients with no

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obstruction at rest, myectomy was performed either because of symptoms and dynamic obstruction at low-load exercise (2 patients) or as included in mitral regurgitation surgical correction. All the other patients (58.9%) were referred for surgery with preoperative diagnosis of asymmetric septal hypertrophy, and in this group, there were 24 (72.7%) patients with severe aortic valve stenosis. Seven (12.5%) patients had the diagnosis of isolated asymmetric septal obstructive hypertrophy, and all of these had previous history of systemic hypertension. This last diagnosis was made in patients with strict basal septal (≥15 mm) hypertrophy and left ventricular outflow obstruction, with no family history of HCM, nonspecific ECG findings, and no other echocardiographic abnormalities. Two of the patients had also the diagnosis of subaortic membrane. Twenty-five (44.6%) patients had previous history of systemic hypertension, and 3 of them had previous myocardial infarction. All patients were symptomatic with predominance of fatigue or dyspnea (37 patients). Nine (16.1%) patients had syncope before surgical intervention. Electrocardiographic criteria for left ventricle hypertrophy were present in 71.4% as assessed by Sokolow–Lyon and/or Cornell criteria [12,13]. By M-mode echocardiography, mean left ventricular mass index was 190.6±51.9 g/m2 and basal septal thickness was 18.8 ±4.9 mm. Intraventricular obstruction at rest measured with continuous wave Doppler was present in 27 (48.2%) patients with a mean gradient of 85.2±39 mmHg. Comparative clinical, ECG, and echocardiographic findings between patients with and without previous diagnosis of HCM are shown in Table 1. Significant differences were found between the presurgical diagnoses of asymmetric septal hypertrophy, including seven patients without aortic valve stenosis, versus HCM. Patients with HCM diagnosis were significantly younger and had higher prevalence of significant intraventricular obstruction at rest and moderate to severe mitral regurgitation. 3.2. Surgical data Transaortic approach was the method of exposure for myectomy in the whole group of patients. All with severe aortic valve stenosis were submitted to both aortic valve replacement and septal myectomy. Isolated myectomy was performed in 12 patients (21.4%), and mitral valve intervention (valvuloplasty, leaflet or papillary muscle shaving, chordae division or replacement) was included in the surgical protocol in 12 patients (2 of the patients with aortic valve stenosis with concomitant mitral valve intervention described as valvuloplasty and papillary muscle shaving). In patients with mitral-valve-associated procedures, intraoperative transesophageal echocardiography was also performed. In surgeons’ procedure reports, there was no particular mention addressing specific septal morphology or appearance. Surgical-related complications occurred in eight of the patients (new-onset left bundle branch block in four patients; high-grade

atrioventricular block requiring pacemaker implantation in two patients; one patient with a small ventricular septal defect; one patient with a septal coronary fistula with no need for intervention).

3.3. Pathology findings Thorough examination of the surgical specimen—endomyocardium, mitral leaflets, chordae or papillary muscles, aortic valve cusps included —was performed.

3.3.1. Macroscopic features Whitish fibroelastic endocardial/subendocardial thickening was observed in the whole group of myectomy specimens and ranged from mild to severe.

3.3.2. Microscopic findings There were no major differences between both groups of patients. There was no recognition of myocardial storage disease both by conventional hematoxylin–eosin and by histochemistry. Neither myocardial infarction nor thrombus was found. Microscopic findings are exhibited in Fig. 1. The majority of patients (n=52; 92.9%) had the final diagnosis of cardiac reactive hypertrophy (Fig. 2). Two (3.6%) of them had the final diagnosis of HCM (Fig. 3). However, one of those with disarray had the presurgical diagnosis of asymmetric septal hypertrophy with aortic valve stenosis. The remaining two (3.6%) patients had the diagnosis of congenital subaortic membranous stenosis with reactive myocardial hypertrophy. When microscopic data were compared among patients with presurgical diagnosis of asymmetric hypertrophy versus HCM, there were no significant differences (Table 2).

4. Discussion In this retrospective work, we tried to assess the myocardial septal histomorphology in a group of patients referred to surgical myectomy with the clinical diagnosis of obstructive sarcomeric HCM or asymmetric septal hypertrophy related to a pressure overload condition. Our main finding was that microscopy is mostly indistinct between both groups, either with the previous diagnosis of cardiomyopathy or with septal hypertrophy in possible relation to left ventricle afterload mismatch, such as in the setting of aortic valve stenosis. Indeed, from our point of view, three discussion topics are raised: (a) different clinical findings between the groups, (b) surgical data, and (c) microscopic features overlap.

Table 1 Clinical, ECG, and echocardiographic findings of both groups of patients, with presurgical diagnosis of asymmetric septal hypertrophy versus presumed diagnosis of HCM.

Age at diagnosis (y) Male gender History of systemic hypertension Severe aortic stenosis History of syncope ECG hypertrophy Left bundle branch block History of atrial fibrillation Left ventricular mass (g/m2) Interventricular septal thickness (mm) Presence of obstruction Presence of mitral regurgitation (any grade) Moderate or severe mitral regurgitation a

Asymmetric septal hypertrophya n=33

HCM n=23

P value

70.2±13.3 11 (33.3%) 21 (63.6%) 24 (72.7%) 4 (12.1%) 26 (78.8%) 4 (12.1%) 9 (27.3%) 191.4±53.6 17.0±4.3 8 (24.2%) 18 (54.5%) 5 (15.2%)

56.4±15.9 8 (34.8%) 10 (43.5%) 2 (8.7%) 5 (21.7%) 14 (60.9%) 6 (26.1%) 4 (17.4%) 189.4±50.9 18.6±6.5 20 (87.0%) 14 (60.9%) 9 (39.1%)

b.001 .567 .111 b.001 .274 .123 .162 .298 .963 .153 b.001 .423 .043

In this group of patients, asymmetric septal hypertrophy could be secondary to aortic valve stenosis, subaortic membrane, and systemic arterial hypertension.


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Fig. 1. Microscopic findings of the whole group of patients. Data are expressed in absolute number of patients with the specified finding.

4.1. Clinical findings Extended left ventricular septal myectomy is currently the treatment of choice for symptomatic obstructive HCM, being the preferred first-line therapy according to American College of Cardiology Foundation/American Heart Association guidelines (Class IIa of recommendation, level of evidence C) [9,14,15]. In experienced centers, mortality is below 1% and complications are uncommon (lower than 2%), except for the occurrence of postoperative partial or complete left bundle branch block [16]. However, this procedure is increasingly performed beyond the classical idiopathic hypertrophic subaortic stenosis, in conditions with left ventricular hypertrophy with septal predominance such as aortic valve stenosis or systemic hypertension. In fact, it has been reported that both left ventricular mass regression and diastolic function were significantly improved in patients who underwent concomitant septal myectomy with aortic valve replacement as compared with those with aortic valve replacement without septal intervention [3,17,18]. The group of 23 patients who were referred to surgical myectomy because of obstructive HCM was younger, had higher prevalence of intraventricular obstruction, and more often had moderate to severe mitral regurgitation. This presurgical diagnosis was made according to several clinical data, and only two patients had concomitant diagnosis of aortic valve stenosis, which could hinder cardiomyopathy diagnosis. On the other hand, aortic valve stenosis was significantly predominant in patients with asymmetric septal hypertrophy, and myectomy was made in accordance to septal thickness description and/or as the surgeon decision during transaortic approach. As it is recognized, possible associated subvalvular obstruction is not always obvious in this setting

until after aortic valve replacement [19], and this should be kept in mind when planning to perform concomitant septal myectomy. In the remaining seven patients with no obvious diagnosis of obstructive HCM and asymmetric septal hypertrophy, some of them could actually have the diagnosis of isolated hypertrophy of the basal ventricular septum. However, we should emphasize that this assumption was merely based in presurgery clinical and echocardiographic data, following a mostly nonconsensual definition, as mentioned above. Current guidelines generally define HCM as any hypertrophy in the absence of a cardiac or systemic overload condition. Still, asymmetric hypertrophy with left ventricular septum to posterior wall ratio exceeding 1.5 is a major criterion for HCM, and it is increasingly recognized in elderly patients with less typical forms of the disease. In this way, only complementary data provided by genetic testing and detailed morphological and functional assessment, by advanced imaging tools, can help distinguish the two entities. As previously reported, even the presence of left ventricular outflow tract obstruction to identify HCM patients is not supported by any data [7]. Age group follows the usual time of disease presentation since acquired valve disease typically occurs three to four decades later than symptomatic obstructive HCM [5]. On the contrary, in older patients with left ventricular hypertrophy and a history of systemic hypertension or aortic valve stenosis, coexistence of HCM must be ruled out, especially when marked septal and asymmetric wall thickness or obstruction is present [3]. However, cardiomyopathy diagnosis is difficult to achieve in this context when supportive clinical data are absent. As this was the case with our group of patients, it should be noted that clinical presentation was not different between groups, as ECG hypertrophy criteria, despite frequent, were also not significantly different.

Fig. 2. Cardiac reactive hypertrophy. (A–B) Myocardial hypertrophy with no significant interstitial fibrosis; (C) mild subendocardial fibroelastosis (*). HE, hematoxylin-eosin; MT, Masson’s Trichrome; EvG, elastic van Gieson’s.

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Fig. 3. Microscopic findings typical of sarcomeric HCM as assessed by the presence of myocardial hypertrophy and disarray (A), interstitial fibrosis (B), thick-walled interstitial vessels (C), and severe subendocardial fibroelastosis (*) (D).

In fact, as it is known, ECG abnormalities do not correlate with hypertrophy severity or pattern as determined by echocardiography [20]. Moreover, echo septal thickness was also not distinctive. As it is mentioned, the likelihood of concomitant cardiomyopathy should be determined by identification of a diagnostic sarcomere mutation or inferred by massive left ventricular thickness (above 25 mm in the case of concomitant severe aortic valve stenosis) and/or intraventricular obstruction with systolic anterior motion and mitral–septal contact [4,21]. Anyhow, significant left ventricular outflow obstruction may be difficult to assess in the presence of severe aortic valve stenosis, and this is why mitral valve dysfunction may be regarded as important for both differential diagnosis and therapeutic target.

patients [16,22], as this was the case in our group of HCM patients. Furthermore, significant mitral valve regurgitation was more prevalent in patients without aortic valve disease, and this further emphasizes specific mitral valve disease involvement in this setting. Only two patients with aortic valve stenosis had mitral valve intervention, and it could be related to concomitant degenerative mitral valve disease, despite not being specified. In the remaining two patients with subaortic stenosis, there was no mitral valve intervention, even though mitral apparatus abnormalities with rotation and anterior displacement are also described in this particular entity [23]. Overall, detailed assessment of the mitral valve could be useful when trying to define preoperatively the cause of septal hypertrophy, as mitral apparatus abnormalities should not be present in pure pressure overload.

4.2. Surgical data 4.3. Microscopic findings Distinctive mitral valve and its support apparatus’ abnormalities are key features in HCM phenotypes. The physiopathology of obstruction is complex in this context, being mainly explained by the interaction between interventricular septum and the mitral valve itself. This is why additional surgical approaches are valuable when treating these

No findings suggesting metabolic or infiltrative storage diseases were observed, though histomorphology may be useful for the identification of rare disorders with specific therapeutic targets and eventual reversible phenotype.

Table 2 Microscopic findings across both groups of patients

Endocardial/subendocardial fibrosis/fibroelastosis Mild Moderate Severe Interstitial fibrosis Focal replacement fibrosis Disarray Vascular hyperplasia Neovascularization Myofibroblast proliferation Fat infiltration

Asymmetric septal hypertrophy n=33

HCM n=23

P value

15 (45.5%) 6 (18.2%) 5 (15.2%) 4 (12.1%) 8 (24.2%) 3 (9.1%) 1 (3.0%) 1 (3.0%) 2 (6.1%) 1 (3.0%) 2 (6.1%)

12 (52.2%) 2 (8.7%) 8 (34.8%) 2 (8.7%) 4 (17.4%) 3 (13.0%) 1 (4.3%) 3 (13.0%) 0 0 1 (4.3%)

.412 .276 .083 .521 .393 .497 .657 .183 .343 .589 .635


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There are few data specially addressing histological evaluation of myectomy specimens, and small studies have shown that there is no single microscopic finding or pattern that could provide differential diagnosis between HCM and cardiac hypertrophy in the setting of abnormal loading conditions [1,24]. In our study, histology was mainly not able to distinguish between different clinical entities and hypertrophy etiologies. This reinforces that clinical diagnosis of sarcomeric HCM should be supported by features such as family history, mitral valve abnormalities, abnormal tissue characterization at cardiac magnetic resonance, tachyarrhythmia, and ultimately genetics. Furthermore, we would also not expect to make the diagnosis of isolated hypertrophy of the basal ventricular septum by histology in patients who were submitted to septal myectomy because of asymmetric septal hypertrophy without aortic valve stenosis. Only combined data from imaging studies might help to clarify the presence of isolated septal hypertrophy. As it was mentioned, this entity actually shares several morphological features with HCM, which hinders diagnosis [7]. Significant overlap was noted among microscopic findings in the whole group of patients. Even “disarray,” typical of HCM, may not be present or may appear focally as a nonspecific feature at the interventricular septum [9,25]. In our study, only two patients had the final histological diagnosis of sarcomeric HCM, and one of the patients with aortic stenosis also showed myocardial disarray. Being defined as a haphazard alignment of adjacent myocytes with myofibrils crisscrossing and branching, it should be noted that several features might compromise its accurate diagnosis: there are four main histological types; three-dimensional architecture affects fiber disposition and the plane of histological sectioning; it may occur in normal hearts, particularly at septal right and left ventricle fiber junction, as well as in conditions that result in increased myocardial mechanical stretch. No strict relation was found between disarray and wall thickness in terms of extend and distribution [8,9,11]. Like in two previous studies [1,24], considerable overlap also occurred concerning several other microscopic findings, which precluded histomorphology differential diagnosis. As subendocardial fibrosis/ fibroelastosis could be potentially related to collagen and elastin deposition in areas of imposed shear stress, it could be expected to occur predominantly in overload conditions other than in primary muscle disease. However, this was not the case according to presurgical supposed diagnosis. Anyhow, subendocardial thickening could be explained by subaortic mitral contact lesion in elderly patients with asymmetric septal hypertrophy and angulation, as well as in HCM patients with mitral valve anterior leaflet elongation and abnormalities. Increasing amounts of interstitial fibrosis may have direct quantitative relation to septal wall thickness, regional function, and arrhythmogenesis in HCM [26,27]. Yet, this was not particularly assessed in our study, and both interstitial and focal replacement fibrosis, as previously demonstrated, were present, without significant differences, throughout the whole group of patients. As a final word, indistinct pathology findings might be eventually explained by a common pressure overload condition that goes beyond disease definition: a dynamic left ventricular outflow tract obstruction in patients with obstructive HCM; the presence of a fixed obstruction in aortic valve stenosis and subaortic membrane; and increased peripheral vascular resistances in systemic arterial hypertension.

diastolic improvement in patients with “reactive” hypertrophy. Ideally, these patients should have been studied with cardiac magnetic resonance before intervention. This imaging tool would not only better characterize myocardial hypertrophy and support presurgical diagnosis, but it would also provide information towards tissue characterization, namely, defining interstitial and focal replacement fibrosis with both T1 mapping and delayed enhancement, respectively [28]. However, we should underline that further characterization was not possible in the majority of patients, as they were referred to our Surgical Center to perform the septal myectomy (with or without concomitant aortic valve replacement), with strict previous investigations. In the same way, this work reflects the analysis of a heterogeneous group of patients in whom myectomy was performed. The small group of patients with asymmetric septal hypertrophy in the absence of aortic valve disease had by definition the diagnosis of HCM. However, histology was not able to identify or distinguish sarcomeric HCM, as this diagnosis has to rely on a complementary set of data.

5. Limitations

References

This study did not include the genetic analysis of the patients, at least of those presumed to have the diagnosis of HCM following combined clinical data. It also did not include detailed echocardiographic data, namely, related to diastolic function and regional function as assessed by deformation imaging. These could have been of help when trying to better define different septal hypertrophy patterns. Furthermore, it would be useful to perform echocardiographic evaluation after septal myectomy to eventually ascertain left ventricular mass regression and

6. Conclusion Since different myocardial hypertrophy etiologies may share similar pathological expression, our descriptive study completes previous reports and stresses the need for detailed clinical and advanced imagiological assessment when trying to define the best interventional approach. Furthermore, detailed characterization helps to define patient’s follow-up, further therapeutic approach, and family screening. This remains important, as the reason why some patients with a paradigmatic pressure overload condition, such as aortic valve stenosis, or even hypertensive disease, also develop or present with clinically significant asymmetric left ventricular hypertrophy is still unknown. However, anatomopathological evaluation in patients submitted to surgical septal myectomy is important to (a) confirm myocardial hypertrophy; (b) disclose and/or characterize specific hypertrophic patterns, when present; and (c) rule out other diseases, namely, metabolic/infiltrative disorders. Declarations Ethics approval and consent to participate Not applicable Consent for publication Not applicable Availability of data and materials Included within the article Authors’ contributions J.A., M.J.A., M.A., R.R., and R.G. were responsible for original idea, clinical data collection, and manuscript writing. M.A. made surgical interventions. R.G. performed pathological interpretation. All the authors reviewed and approved the final manuscript. Acknowledgments Not applicable

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