Diagnostic capabilities of cardiac computed tomography in the preoperative diagnosis of hypertrophic cardiomyopathy

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BACKGROUND

Rapid advancements in cardiovascular medicine have enabled the introduction of novel and significant therapeutic approaches for diseases previously considered incurable. Cardiomyopathies remain among the least researched cardiovascular diseases. Hypertrophic cardiomyopathy (HCM) is one of the most widely recognized among all genetic diseases. It is accompanied by a set of specific morphological and functional alterations and is characterized by left ventricular (LV) myocardial hypertrophy and/or, less frequently, right ventricular hypertrophy. It is frequently asymmetrical, primarily due to interventricular septum (IVS) thickening and/or involvement of other walls, which may lead to left ventricular outflow tract (LVOT) obstruction [1]. Advances in HCM-related study in conjunction with the evolution of diagnostic techniques have led to the progressive integration of clinical, pathological, and physiological features into a unified theory of coherent diseases [2]. The American Society of Cardiovascular Imaging consensus guidelines state that, if institutional resources and adequate expertise are available, cardiac magnetic resonance imaging (MRI) should be used for the initial evaluation of patients with HCM (grade of recommendation I, level of evidence B) [3]. For patients with HCM for whom MRI is contraindicated or technically impractical, contrast-enhanced computed tomography is recommended for assessing linear morphometry and cardiac function (grade of recommendation IIa, level of evidence C) [3]. With balanced contrast enhancement of both ventricular cavities in a single scan, multislice computed tomography angiography (MSCT-A) is a highly informative technique that enables a thorough assessment of the cardiac chamber anatomy, valvular structures, and coronary circulation in patients with HCM. Furthermore, MSCT-A is superior to MRI in evaluating LV anatomy, particularly in the midventricular phenotype of HCM, where it can detect alterations in LV morphology and configuration, such as the “dumbbell” appearance with significant systolic narrowing in the midventricular segment. In patients with the midventricular phenotype of HCM, apical aneurysms are frequently observed because of a sharp rise in systolic pressure caused by midventricular obstruction [4]. The phenotypic features of HCM include a significant association with ventricular arrhythmias, myocardial necrosis, and systemic embolism [5]. Research on the application of delayed contrast enhancement to identify fibrotic myocardial areas in patients with HCM has appeared since the publication of a study demonstrating that dual-energy computed tomography (DECT) can successfully detect myocardial fibrosis in acute myocardial infarction in patients with HCM [6, 7]. A comparative study revealed that DECT angiography provides high diagnostic accuracy, comparable to that of cardiac MRI, in assessing linear and functional parameters as well as structural myocardial abnormalities [8]. The primary limitation of DECT angiography is its lower temporal resolution and reduced soft tissue contrast [8]. The implementation of innovative technologies and computational methods in next-generation scanners with dual-energy sources and a reduced contrast agent volume is becoming a relevant and promising strategy, creating safer conditions for assessing structural myocardial abnormalities in patients with HCM.

AIM

To study the potential of computed tomography for preoperative diagnosis of phenotypic forms of HCM as a substitute for cardiac MRI.

MATERIALS AND METHODS

The Federal State Budgetary Institution A.N. Bakulev National Medical Research Center for Cardiovascular Surgery of the Ministry of Health of the Russian Federation has accumulated extensive experience in the surgical treatment of HCM, employing a range of operative techniques in conjunction with the correction of cardiac rhythm disorders [9]. A retrospective analysis was conducted on data from 47 patients with HCM (mean age, 52 ± 7 years), including 25 males, from 2015 to 2022. The diagnosis was established by attending physicians in compliance with current guidelines, based on a comprehensive assessment and family history review.

Study Design

A scanning procedure we designed and previously published was used with cardiac MSCT-A in 34 patients with HCM to analyze the morphology of the mitral valve (MV), subvalvular structures, and the architecture of the heart chambers and coronary arteries. The scans were conducted on SOMATOM Definition Flash (Siemens Healthineers, Germany) and Brilliance iCT 256 (Philips, Netherlands) scanners [11]. Automatic bolus tracking of the contrast agent was performed in the left atrium, with a predefined threshold of 90 HU, followed by two-phase sequential administration (Fig. 1).

 

Fig. 1. Computed tomography images of premonitoring and monitoring graphs: a — automatic bolus tracking system in the left atrial cavity with a threshold of 90 HU; b — example of a bolus tracking graph.

 

To assess structural alterations in the LV myocardium, a retrospective DECT analysis was performed in 13 patients with HCM who underwent imaging with a second generation dual-source scanner (SOMATOM Force; Siemens Healthineers, Germany). The following scanning parameters with retrospective electrocardiography gating were applied:

• Tube voltage on the first X-ray tube: 100 kV, tube current–time product: 160 mAs;
• Tube voltage on the second X-ray tube: 140 kV, tube current–time product: 130 mAs;
• Collimation: 64 × 0.6 mm;
• Tube rotation time: 0.33 s.

There were two phases to the scanning protocol: angiographic and delayed. Using a SOMATOM Definition Flash scanner (Siemens Healthineers, Germany), the first (angiographic) phase was carried out in accordance with a previously validated protocol (Fig. 2).

 

Fig. 2. Example of postprocessing in cardiac computed tomography angiography in a patient with hypertrophic cardiomyopathy. Visualization of the cardiac chambers, coronary arteries, and papillary muscle heads: a — 3D reconstruction of the four-chamber heart view; b —3D reconstruction of the coronary arteries; c —multiplanar reconstruction in a two-chamber heart view. LA, left atrium, LV, left ventricle, RA, right atrium, RV, right ventricle.

 

Seven minutes following the angiographic phase, the second (delayed) scanning phase was conducted to assess structural changes in the LV myocardium. The scanning area and field of view were adjusted considering each patient’s heart size. By default, the mid-diastole phase was employed as the reconstruction phase with high- and low-energy tube voltage in the axial plane, using the following parameters: slice thickness, 0.75 mm; interval, 0.5 mm; and reconstruction filter, D30f. DECT iodine mapping was performed on a workstation (Syngo.via VB30A; Siemens Healthineers, Germany) using the Heart PBV (perfused blood volume) application. Images from the delayed scanning phase were reformatted onto the short-axis plane with a slice thickness of 8 mm and 0.5 mm intervals (Fig. 3).

 

Fig. 3. Dual-energy computed tomography iodine maps: a — four-chamber heart view (ROI, region of interest—iodine distribution measurement in the left ventricular cavity and interventricular septum); b — short-axis heart view (ROI, iodine distribution measurement in the left ventricular cavity and interventricular septum).

 

Main Study Outcome

All the patients with HCM were classified into five morphological types using the 17-segment LV model, in accordance with the American Heart Association classification [10]. In each patient, the chordo-papillary apparatus anatomy was examined.

Statistical Analysis

The study data were subjected to statistical processing applying both parametric and nonparametric approaches. Statistical analysis was performed in the Microsoft Excel software (Microsoft Inc., USA). Quantitative variables are presented as means (M) and standard deviations. Pearson’s correlation coefficient (r) was utilized to determine the relationship between categorical variables.

RESULTS

Participant Characteristics)

Table 1 provides a summary of the study cohort’s (n = 47) key parameters as determined by MSCT-A and DECT.

 

Table 1. Linear and Volumetric Cardiac Parameters in the Study Group of 47 Patients

Parameter	Value
Left ventricle
LV EDD, mm	41.14±4.6
LV ESD, mm	20.4±5.2
LV EDV, mL	114.9±47.1
LV ESV, mL	28.8±14.0
LV SV, mL	85.7±38.0
LV EF, %	67.5±22.0
LV posterior wall thickness, mm	13.5±5.7
IVS thickness, mm	18.32±5.6
LVOT diameter, mm	24.7±2.8
LVOT area, cm2	3.2±0.6
Left atrium
Anteroposterior diameter, mm	50.9±7.6
Mediolateral diameter, mm	63.2±10.3

Note: LV, left ventricle; EDD, end-diastolic diameter; ESD, end-systolic diameter; EDV, end-diastolic volume; ESV, end-systolic volume; SV, stroke volume; EF, ejection fraction; IVS, interventricular septum; LVOT, left ventricular outflow tract.

 

Primary Findings

Morphological variants of HCM were identified based on the localization of LV myocardial hypertrophy on CT. Our findings demonstrate the phenotypic heterogeneity of HCM, conventionally categorized into five morphological types, though not limited to these classifications. Most patients — 26 out of 47 (55%)—exhibited a diffuse septum morphological phenotype of HCM (Fig. 4).

 

Fig. 4. Example of 3D computed tomography images of the diffuse septum phenotype of HCM: a — two-chamber view of the left heart; b — short-axis heart view; c —four-chamber heart view. LV, left ventricle; LA, left atrium; RV, right ventricle; RA, right atrium.

 

Five out of 47 patients (11%) had the midventricular phenotype (Fig. 5), including two (40%) with midventricular hypertrophy accompanied by LV apical bulging/aneurysm.

 

Fig. 5. Example of MPR and 3D computed tomography images of the midventricular phenotype of hypertrophic cardiomyopathy with signs of systolic cavity obstruction because of a variant anomaly of the chordo-papillary apparatus and asymmetric left ventricular myocardial hypertrophy: a — two-chamber view of the left heart; b — three-chamber heart view; c — four-chamber heart view. Apical displacement of the posterolateral papillary muscle with direct contact with the anterior mitral leaflet; splitting of papillary muscle heads and an additional muscular trabecula.

 

In eight out of 47 (18%) patients, an asymmetric variant of the focal basal phenotype of HCM with an S-shaped/”sigmoid” IVS was detected, characterized by myocardial hypertrophy of the septal segments at the basal level close to the LVOT (Fig. 6).

 

Fig. 6. Example of 3D computed tomography images of the focal basal phenotype of hypertrophic cardiomyopathy: a — two-chamber view of the left heart; b — short-axis heart view.

 

A concentric phenotype, which is defined by symmetrical hypertrophy of the LV walls with a decreased cavity, was seen in four out of 47 patients (8%). Another four (8%) patients exhibited an apical phenotype (Fig. 7).

 

Fig. 7. Example of MPR and 3D computed tomography images of a patient with the apical phenotype of hypertrophic cardiomyopathy after implantable cardioverter-defibrillator placement: a — four-chamber heart view; b — two-chamber view of the left heart; c — 3D VRT reconstruction of the four-chamber heart view.

 

Our study found that patients who underwent myectomy as surgical treatment of HCM typically exhibited a diffuse septum phenotype. All patients with the midventricular phenotype underwent surgical correction using the method outlined by L. A. Bokeria, while those with the focal basal phenotype underwent combined defect correction, including MV replacement or repair, the Morrow procedure, and subvalvular MV apparatus excision.

Extreme hypertrophy ≥30 mm was detected in two out of the 47 (4%) patients with HCM. In accordance with the approach of C. Harrigan and G. Efthimiadis, we examined the magnitude of myocardial hypertrophy in HCM based on MSCT-A and DECT data and established that hypertrophy was more pronounced in patients with the obstructive type of HCM [11].

Secondary Findings

When evaluating the linear parameters of the MV in the population under study, the mean mitral annulus size was 36.8 ± 6.6 mm in the four-chamber view and 37.6 ± 6.5 mm in the two-chamber view. The mitral annulus opening area was 8.8 ± 2.9 cm^², the anterior mitral leaflet (AML) length was 28.9 ± 3.1 mm, and the posterior mitral leaflet (PML) length was 20.8 ± 3.4 mm. The morphological type of chordal apparatus and papillary muscles (PM), as well as the type of PM positioning, were determined in all patients.

Based on the study results, four groups of chordo-papillary apparatus abnormalities were identified [13, 16].

1. Six patients (13%) in the first group included had undivided papillary muscles and distinct chordae connecting the ventricular surface and the free edge of the MV leaflets to the PM head.
2. The second group comprised 23 patients (49%) with the so-called split form of PM, characterized by multiple accessory PM, with one head directly attached to the PML and the others to the commissural area of the AML.
3. The third group consisted of 13 patients (27%) with PM division into several heads, atypical direct attachment of one head to the mitral commissure, disproportionate elongation of the MV chordae resulting in prolapse, and leaflet hypermobility (AML prolapse into the LVOT).
4. The fourth group included five patients (11%) and was characterized by a PM complex with sequential divergence of well-differentiated heads, clearly visible in short-axis heart images.

Notably, based on DECT data, five patients (38%) from the third group of chordo-papillary apparatus abnormalities in the current study underwent surgery for HCM, which was supplemented with PM reorientation and fixation of mobile PM to the posterior LV wall.

All patients underwent coronary artery assessment. The mean diameter of the left coronary artery (LCA) ostium was 3.7 ± 2.3 mm, while that of the right coronary artery was 2.6 ± 1.8 mm. No significant differences were discovered between the CT and selective coronary angiography parameters (p > 0.05) (Table 2).

 

Table 2. Comparative Analysis of Coronary Artery Anatomy and Pathology Utilizing Computed Tomography and Selective Coronary Angiography

Parameter		Computed Tomography, n=47	Coronary Angiography, n=47	p
Ostial anomaly		2% (1)	2% (1)	1.0000
Type of blood supply	Right-dominant	85% (40)	87% (41)	0.5371
	Left-dominant	11% (5)	11% (5)	1.0000
	Balanced	4% (2)	2% (1)	0.3458
Atherosclerosis and calcification of the coronary arteries		28% (13)	34% (16)	0.5015

 

Analysis of coronary artery anatomy revealed an intramyocardial course of the LCA in ten patients (21%), with signs of dynamic narrowing observed in three patients (14%).

Aortic valve morphology assessment is crucial for planning myectomy in patients with HCM. We found that the mean diameter of the aortic valve annulus was 29.1 ± 3.4 mm. A weak correlation was found between LVOT size and the diameter of the aortic valve annulus (r = 0.2, p > 0.05). Additionally, signs of LVOT obstruction due to IVS hypertrophy and thickening of LV muscular trabeculae were detected in 29 patients (62%).

Structural myocardial changes were studied using DECT in 13 patients (27%). All patients exhibited focal iodine accumulation on delayed contrast enhancement maps (Fig. 8).

 

Fig. 8. Example of visual assessment of focal iodine accumulation in left ventricular myocardial segments based on dual-energy computed tomography iodine mapping: a — short-axis heart view; b — axial heart view.

 

Ten out of 13 patients (76%) exhibited focal areas of intramyocardial iodine accumulation localized in the IVS. Extracellular volume fraction (ECV) was calculated at the midventricular level utilizing delayed iodine enhancement maps. The ECV value was determined using the following equation:

$ECV=\frac{\Delta H{U}_m}{\Delta H{U}_b}\times \left(1-hematocrit\right)\times 100\%,$

where ΔHU_m and ΔHU_b represent iodine attenuation in the LV myocardium and in the LV cavity, respectively.

Ten of 13 patients (76%) in our study exhibited an elevated ECV in one or more segments (N = 25.4%). The mean ECV of the LV myocardium, as assessed by DECT, was 30.58% (95% CI, 27%–34%), which exceeded the normal reference ranges.

DISCUSSION

In contemporary cardiovascular surgery, a thorough investigation of HCM utilizing cutting-edge diagnostic tools and scanning techniques ensures high-quality monitoring and treatment efficacy for patients with HCM. Presently, MRI enables the assessment of major macroscopic abnormalities of the LV myocardium, including segmental thickening and replacement fibrosis in delayed contrast phases, as well as alterations in the cellular and extracellular myocardial space through T1 mapping with relaxation time assessment, which specifically detects diffuse myocardial fibrosis (grade of recommendation IIa, level of evidence B) [3]. Despite its advantages, MRI has numerous absolute and relative contraindications [12]. Absolute contraindications to use of MRI include MRI-incompatible pacemakers, cerebral clips, cochlear implants, and other metal-containing devices or implants [12]. Additionally, cardiac imaging is still unavailable in many medical centers despite the increasing availability of MRI. MSCT-A offers a wide range of clinical applications due to its ability to assess both anatomical and functional cardiac properties. However, this method is recommended only in cases of diagnostic uncertainty, poor acoustic windows on echocardiography, and/or contraindications to cardiac MRI. Consequently, cardiac MSCT-A is rarely used as a primary diagnostic tool for patients with HCM. Nevertheless, DECT with iodine mapping can be regarded as an alternative imaging technique for evaluating LV myocardial structural abnormalities [13]. Additionally, computed tomography should be incorporated into the multimodal diagnostic strategy before surgery in patients with HCM undergoing extended myectomy with subvalvular mitral apparatus resection [14]. This method provides precise answers to key questions for cardiac surgeons, such as the type, location, and substrate of obstruction in patients with HCM (i.e., MV and PM abnormalities), allowing for preoperative modifications of surgical maneuvers and the selection of the optimal approach to LV obstruction relief. A comprehensive preoperative assessment of LV anatomy can optimize the diagnostic workflow, lowering both the time and number of diagnostic procedures required in the preoperative period.

In our study, most patients exhibited a diffuse septum morphological phenotype of HCM, characterized by IVS hypertrophy. This phenotype is frequently linked with a mixed type of obstruction, occurring at both the LVOT and intraventricular levels [15], occasionally accompanied by a prominent noncompacted layer of the LV lateral wall [16]. Furthermore, a substantial proportion of patients in the study group had a focal basal phenotype of HCM with an S-shaped/“sigmoid” IVS, characterized by hypertrophy of the septal segments at the basal level near the LVOT. This variant may cause subaortic obstruction and mitral regurgitation [16]. Only five patients were diagnosed with the midventricular phenotype, which is defined by LV midventricular segment hypertrophy, resulting in localized LV cavity narrowing and apical dilatation. A distinctive feature of this HCM phenotype is its high incidence of ventricular arrhythmias, myocardial necrosis, and systemic embolism [4]. A minority of patients had the apical phenotype, which is characterized by complete or partial obliteration of the LV cavity in the apical segments. This phenotype is believed to have a better prognosis than other variants, even though it is more strongly related to ischemia and LV apical myocardial infarction [10].

The study of variant anatomy of the chordo-papillary apparatus of the MV is critical for developing surgical techniques for HCM correction. Abnormal chordal attachment to the base of the AML, AML length, and a greater mobility angle of the anterolateral papillary muscle (AL-PM) have been shown to be significantly associated with dynamic LVOT obstruction, independent of other factors, including IVS thickness [18]. Additionally, AML elongation has been observed to correlate with abnormalities of the MV subvalvular structures (including thickening of the PM heads) and atypical attachment of the PM heads/chords in patients with HCM [18]. A surgeon’s understanding of MV anatomical features aids in preoperatively determining the feasibility of MV preservation or planning for valve replacement to ensure complete elimination of the LVOT gradient. Previous findings from our center suggest that in patients with HCM, a reduction in LVOT area (<2.6 cm²) and an increase in AML length (>27 mm) can predict LVOT obstruction (≥30 mm Hg) [14].

The occurrence of myocardial ischemia in patients with HCM is currently a well-established fact [19]. Notably, the intramyocardial course of the coronary arteries leads to their compression during systole, resulting in coronary insufficiency and even sudden cardiac death [1]. In our study, an intramyocardial course of the LAD branch of the LCA was identified in ten patients.

The pathological structural remodeling of the myocardium, known as fibrotic myocardial remodeling, is largely caused by alterations in the extracellular matrix (ECM) and coronary microcirculation. The calculation of the extracellular volume fraction (ECV) in each LV myocardial segment is a promising tool for the quantitative evaluation of fibrotic remodeling. Recent publications demonstrate growing interest and efforts in incorporating an alternative myocardial structural imaging modality—DECT with iodine mapping—into the diagnostic algorithm for patients with HCM [20, 21]. DECT-derived normal reference ECV values in the LV myocardium have been reported to be 25.4% [13, 20]. In our study, ten patients who were evaluated using DECT exhibited elevated ECV values in one or more segments. A study conducted at Northwestern University Feinberg School of Medicine showed that, based on histological data, diffuse LV myocardial fibrosis was more prevalent in patients with HCM who died of sudden cardiac death than in those with hypertension-related LV myocardial hypertrophy who died due to non-cardiovascular-related etiologies. This implies that high ECV values may serve as a base for arrhythmia [22].

Study Limitations

This study includes data from patients treated at a single medical center. The data was collected using two computed tomography scanners with specially developed protocols. The reproducibility of these results in diverse clinical settings evidently requires further investigation.

CONCLUSION

The accuracy of HCM diagnosis using computed tomography depends on appropriately selected scanning parameters. Our scanning protocols, developed for CT scanners of different generations, enable the identification of distinctive morphological HCM patterns in a single study. Additionally, they allow for a detailed assessment of chamber and valvular geometry, LV function, coronary anatomy, and structural alterations in the LV myocardium. This method provides cardiac surgeons vital information regarding the origin and location of potential dynamic obstruction, which is essential for selecting the optimal surgical strategy.

ADDITIONAL INFORMATION

Funding source. This study was not supported by any external sources of funding.

Competing interests. The authors declare that they have no competing interests.

Authors’ contribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work. O.Yu. Dariy — development of the article concept, writing the text; L.A Yurpolskaya— writing and reviewing the text; I.E. Rychina — development of the article concept; A.V. Dorofeev, E.Z. Golukhova — approval of the final version of the text.

About the authors

Olga Y. Dariy

Bakulev Scientific Center for Cardiovascular Surgery; Research and Practical Clinical Center for Diagnostics and Telemedicine Technologies

Email: dariiolyka@mail.ru
ORCID iD: 0000-0003-0140-8166
SPIN-code: 1844-4944

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; Moscow

Liudmila A. Yurpolskaya

Bakulev Scientific Center for Cardiovascular Surgery

Email: layurpolskaya@bakulev.ru
ORCID iD: 0000-0001-7780-2405
SPIN-code: 8436-9665

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow

Inna E. Rychina

Bakulev Scientific Center for Cardiovascular Surgery

Email: ierychina@bakulev.ru
ORCID iD: 0000-0001-8056-4188
SPIN-code: 3516-0729

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Aleksey V. Dorofeev

Bakulev Scientific Center for Cardiovascular Surgery

Email: avdorofeev@bakulev.ru
ORCID iD: 0000-0003-0833-9650

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Elena Z. Golukhova

Bakulev Scientific Center for Cardiovascular Surgery

Author for correspondence.
Email: egolukhova@bakulev.ru
ORCID iD: 0000-0002-6252-0322
SPIN-code: 9334-5672

MD, Dr. Sci. (Medicine), Academician of Russian Academy of Science

Russian Federation, Moscow

References

Supplementary files