Hypertrophic cardiomyopathy (HCM) is a primary cardiac disorder characterized by myocardial hypertrophy in the absence of any detectable increase in afterload (i.e., systemic hypertension or aortic stenosis). Still considered a disease burden worldwide, HCM has an estimated population prevalence of 0.2% (1/500) and is among the most common causes of sudden cardiac death (SCD), especially in patients under 35 years of age [1]. Therefore, the early and accurate diagnosis of HCM is crucial in the direction of care, timely treatment, and preventing complications.

HCM is divided into obstructive and non-obstructive groups based on peak gradient at the left ventricular outflow tract (LVOT) or mid-left ventricular cavity. LVOT obstruction is defined as a gradient greater than 30 mmHg that can lead to adverse outcomes. Usually, echocardiography is used to assess LVOT obstruction; however, echocardiography may not always be sufficient to diagnose HCM definitively, particularly in patients whose ultrasound window is limited and whose signs of hypertrophy are unclear [2]. In recent years, the emergence of cardiac magnetic resonance (CMR) imaging has overcome these echocardiography limitations and presents many obvious advantages, such as visualization of the myocardium and high reproducibility. CMR is now considered the reference standard for quantifying left ventricular (LV) volume, mass, wall thickness, function, and phenotypic classification. CMR has been recommended to aid echocardiography in definitive diagnosis, differential diagnosis, and treatment of HCM [3]. However, the correlation between the LVOT/aortic valve (AO) diameter ratio on CMR imaging and the LVOT pressure gradient (PG) on echocardiography has yet to be assessed adequately. In addition, HCM phenotypes vary among Europeans and Asians [4] and different countries within Asia [5, 6]. Therefore, we conducted this study to provide additional information on the imaging characteristics of HCM in Asians and evaluate the correlations of selected CMR parameters with echocardiography.

In this cohort, the 46 patients diagnosed with HCM had an average age of 51.2 $\pm$ 18.43 years. The male-to-female ratio was 1:4, which was consistent with the study by Corona-Villalobos et al. [7]. HCM is caused primarily by an autosomal dominant mutation that can be passed to the next generation; the risk is 50% if either parent has HCM [8]. In this study, 32.5% of the patients had a family history of HCM, 30.4% had a family history of SCD, and 2.2% had a family history of implantable cardioverter–defibrillator use, rates that were notably higher than those reported by Chan et al. [9], who found rates of 13.3%, 3.9%, and 2.2% respectively. The rates reported in this study were also much higher than those reported by Alashi et al. [10], who found a family history of HCM and SCD in 2% and 5% of cases, respectively. These differences could be attributable to variations in sample size, study subjects, and research locations. In particular, Alashi et al. [10] recruited 1110 older patients aged 75–92 years (mean: 80 $\pm$ 5 years) in the United States. Chan et al. [9] recruited 564 Chinese children with a median age at diagnosis of 1.0 years.

In this study, patients experienced syncope, dyspnea, and chest pain as their most common symptoms. The prevalence of dyspnea, at 73.9% (approaching New York Heart Association class II), was comparable to findings reported by Alashi et al. [10]. However, the rates of chest pain and syncope in the current study (78.3% and 23.9%, respectively) were higher than the 19% and 12% reported in the study by Alashi et al. [10], although the variations in age distribution and a higher proportion of patients with heart failure in the current study might have influenced these differences.

Our study revealed a strong negative correlation between LVOT PG on echocardiography and the LVOT/AO diameter ratio on CMR (r = –0.66). Using a receiver operating characteristic curve, we established that an LVOT/AO diameter ratio of 0.38 measured by CMR, with an area under the curve of 0.87, a sensitivity of 87%, and a specificity of 78.3%, allowed for the detection of an LVOT PG 30 mmHg in patients with HCM at rest. To our knowledge, this is one of the few studies that determine a LVOT/AO diameter ratio cut-off value for CMR in assessing LVOT obstruction. In comparison, Vogel-Claussen et al. [11] studied 92 patients and identified an LVOT/AO diameter ratio cut-off point of 0.33, with an area under the curve of 0.91, a sensitivity of 91%, and a specificity of 80%. This variance in cut-off points could be attributable to differences in sample size and patient characteristics.

The mean maximum LV wall thickness observed in this study was similar to the previously reported value of 22 $\pm$ 5 mm [12]. The mid-anteroseptal, mid-inferoseptal, and basal anterior segments had the highest mean thicknesses, whereas the basal inferior segment had the smallest thickness, consistent with values reported by Maron et al. [12]. Bilateral ventricular hypertrophy was present in 6.5% of the patients in this study. The predominant phenotypes were diffuse asymmetric HCM and septal HCM, followed by apical HCM at 6.5%. This ranking aligns with the findings of Thao et al. [13], who observed asymmetric hypertrophy (40.7%), diffuse hypertrophy (44.5%), apical HCM (14.8%), and bilateral ventricular hypertrophy (18.5%) in 27 patients with HCM. Compared with a study of 25 patients with HCM by Kim et al. [14], this study found a similar predominance of diffuse asymmetric HCM (32%) and septal HCM (52%), with a slightly higher prevalence of apical HCM (16%). The proportion of apical hypertrophic cardiomyopathy of 6.5% in our study was lower than those reported in Asia (31%) and Europe (13%) [4]. On the contrary, the proportion of septal hypertrophic cardiomyopathy in this study (37%) was higher than those in Asia and Europe (17% and 28%, respectively) [4]. This difference may be partly attributed to regional variations and the small sample size in the study.

An outstanding advantage of CMR imaging compared with echocardiography is the detection of myocardial fibrosis by LGE, not only in hypertrophic segments but also in non-hypertrophic areas. LGE mass plays a role in disease progression and prognosis and is possibly the cause of ventricular arrhythmias. Half of the study patients had LGE, a proportion lower than that reported by Thao et al. [13] (88.9%), likely because of differences in sample size, study location, time, and disease stage. Some studies have revealed that the rate of LGE varies and can be as high as 60%–70% in adults and 46% in children [13, 15]. These results are similar to those reported by Mentias et al. [16]. The distribution of LGE mainly in the mid-wall of the hypertrophic segments with plaque pattern in the current study accords with findings in a previous series [17]. These features are consistent with the characteristics of nonischemic cardiomyopathy and do not fall into coronary artery territory. The LGE measurement indicated the amount of fibrous tissue, denoting disease progression and prognosis. In this study, the mean LGE mass in the obstructive HCM group was twice that in the non-obstructive HCM group. In addition, native T1 values could reflect histologic remodeling of the myocardium and become widely used in clinical practice [18]. In this study, the native T1 value was higher in the obstructive HCM group than in the non-obstructive HCM group, denoting more advanced myocardial tissue remodeling in the obstructive group.

In cardiovascular disease, echocardiography is a non-invasive, widely available, and valuable diagnostic tool, whereas CMR is a high-cost test that can complement and address the limitations of echocardiography. A LV wall thickness $\ge$30 mm represents a prognostic factor independently associated with SCD. Therefore, accurate wall thickness assessment is pivotal in diagnostic and therapeutic decision-making, such as for pacemaker implantation. In a study that compared maximum wall thickness measured by echocardiography and CMR, the discrepancy ranged from 3 mm to 17 mm, indicating that methodology differences could affect treatment decisions [19]. Echocardiography has been reported to potentially either overestimate or underestimate HCM because of the challenges in obtaining optimal images for all LV areas [19, 20]. Since measurement discrepancies can influence diagnosis and treatment, CMR is increasingly considered a routine investigation for all patients with HCM, particularly when the ultrasound window is limited. In this study, we observed no differences in the EF values obtained using the two methods. This finding contrasts with a study by Jenkins et al. [21], in which EF measured by CMR and 3 dimension (3D) echocardiography demonstrated accuracy superior to that obtained with 2 dimension (2D) echocardiography. The discrepancy might stem from differences in patient populations.

The 2020 American College of Cardiology/American Heart Association guideline outlines seven risk factors for HCM SCD risk stratification, including a family history of sudden death from HCM, wall thickness $\ge$30 mm, unexplained syncope, LV apical aneurysm, extensive LGE on CMR imaging, and non-sustained ventricular tachycardia diagnosed by ambulatory monitor. In this study, echocardiography detected 80.4% of patients at risk of SCD; CMR could identify up to 91.3%, necessitating consideration for pacemaker placement. This observation underscores the superiority of CMR to echocardiography. Further, with its high resolution and ability to delineate fibrous tissue, CMR provides more accurate information. However, in clinical practice, ideal prognostic parameters should be simple and readily available, highlighting structural anomalies such as myocardial fibrosis and systolic and diastolic dysfunction. We therefore aver that an effective SCD screening strategy combines echocardiography and CMR. In this study, 8.7% of patients had extensive LGE ($\ge$15% of LV mass), independently predicting SCD risk in patients with HCM. In a study that followed 1293 patients with HCM for over 3.3 years, every 10% increase in LGE mass was associated with a 1.46 increased risk of SCD [22], underscoring the prognostic significance of LGE.

This study further identified a negative correlation between the LVOT/AO diameter ratio according to CMR and the LVOT PG according to echocardiography, consistent with previous reports [11, 23]. SAM of the mitral valve narrows the LVOT, reducing the LV ejection volume. As a compensatory mechanism, the heart contracts rapidly and forcefully, elevating the velocity through the LVOT and resulting in increased LVOT PG. In this study, without examining LVOT PG directly, we found that those with SAM had a 5.7 times greater likelihood of having an LVOT/AO diameter ratio 0.38 than those without SAM. To our knowledge, this is the first study on SAM of the mitral valve on echocardiography to predict LVOT/AO diameter ratio on CMR in patients with HCM.

The LVOT/AO diameter ratio measured by CMR represents a precise index for categorizing hemodynamic HCM groups. The findings of this study suggest that CMR outperforms echocardiography in the stratification of SCD risk.

The datasets analyzed during this study are available from the corresponding author upon reasonable request.

HCM, hypertrophic cardiomyopathy; CMR, cardiac magnetic resonance; LV, left ventricular; LVOT, LV outflow tract; AO, aortic valve; PG, pressure gradient; LGE, late gadolinium enhancement; SCD, sudden cardiac death; SAM, systolic anterior motion.

VDL and PMH, YLW designed the research study. PBN, VTKT, NNT and NKV performed the research. HTVH, NTH and LTTL analyzed the data. PBN, NNT and NTH wrote the manuscript. NNT and YLW revised the manuscript and gave final approval of the version. All authors contributed to editorial changes in the manuscript and approved the final version. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was approved by the Institutional Review Board of the Bach Mai Hospital, Hanoi, Vietnam approval for this study (ID # 2338), and the board decided to waive the requirement for obtaining informed consent, in accordance with the Declaration of Helsinki (1989) by the World Medical Association.

This research received no external funding.

The authors declare no conflict of interest. Yung Liang Wan is serving as Guest Editor of this journal. We declare that Yung Liang Wan had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Sophie Mavrogeni and John Lynn Jefferies.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/j.rcm2509341.