Patterns of Left Ventricular Hypertrophy and Late Gadolinium Enhancement on Cardiac MRI in Patients with Hypertrophic Cardiomyopathy and their Prognostic Significance – An Experience from a South Asian Country

INTRODUCTION

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in young people worldwide. It is a genetic cardiac disease with a heterogeneous phenotypic expression caused by autosomal dominant mutations in contractile sarcomeric proteins. It has a prevalence of 1:500 in general population.^[1,2]. Conventionally, it is diagnosed by the presence of left ventricular (LV) hypertrophy on 2D-echocardiography; however, cardiac magnetic resonance (CMR) is increasingly being used as a specific imaging modality.

CMR is more pertinent not only in the diagnosis of HCM but also in predicting the prognosis by detection of late gadolinium enhancement (LGE). CMR has an edge over echocardiography as it provides more accurate assessment of LV function and LV hypertrophy.^[3] It can also accurately detect the different patterns of LV hypertrophy, that is, asymmetric, symmetric, apical, and mid ventricular.

Worldwide, much data are available on the patterns of hypertrophy and LGE on CMR in HCM. However, there is paucity of data on this topic in our population. This study was conducted to assess the patterns of LV hypertrophy and LGE on CMR, in HCM patients in Pakistani population. We also determined the prognostic significance of LGE in these patients. This is the first study of its kind in Pakistani population. As Aga Khan University Hospital (AKUH) is the first and the only center offering comprehensive CMR services in the country since 2011, so this was the best place to conduct such study.

MATERIAL AND METHODS

This study was conducted after approval from the ethical review committee. All the patients who had undergone CMR at AKUH with the suspected diagnosis of HCM, during the period 2011 to 2019 were identified using Health Information Management Services. Only those patients were included in the study who had confirmed diagnosis of HCM on CMR.

A pre-designed data entry form was filled for each patient after reviewing their medical records. Information was collected regarding age, gender, clinical features at presentation, Electrocardiogram (EKG) findings, echo data, and CMR findings. Follow-up data regarding death, arrhythmias and hospital admissions for heart failure were also collected by reviewing the medical records.

RESULTS

A total of 74 patients who fulfilled the inclusion criteria were included in the study. Baseline clinical and demographic characteristics are summarized in Table 1. Mean age was 45.6 ± 15 years with the majority 71.6 % (n = 53) being male. Dyspnea (62.2%, n = 46) was the main symptom at presentation, followed by syncope (39.2%, n = 29).

Findings of CMR are shown in Table 2. Maximal LV wall thickness was 21.1 ± 5 mm with more than half of patients 56.8% (n = 42) having severe LV hypertrophy. Asymmetrical septal hypertrophy was the most common pattern of hypertrophy present in 62.2% (n = 46) of the patients, followed by septal and anterior wall hypertrophy (17.6%, n = 13). Various patterns of LV hypertrophy are shown in Figures 1-5.

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Figure 1:

A 70-year old male with hypertension presented with history of syncope. Cardiac magnetic resonance steady-state free precession still frame 3chamber view showing asymmetrical septal hypertrophy (arrow).

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Figure 2:

A 55-year old male with history of palpitation and left ventricular hypertrophy on echo. Cardiac magnetic resonance steady-state free precession still frame short axis view showing septal and anterior wall hypertrophy (arrow).

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Figure 3:

A 71-year old male with history of syncope. Cardiac magnetic resonance steady-state free precession still frame 2chamber view showing mid ventricular hypertrophy (arrow).

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Figure 4:

A 38-year old male with history of chest pain, diffuse T wave changes on ECG and normal coronary angiogram. Cardiac magnetic resonance steady-state free precession still frame 2chamber view showing apical hypertrophy (arrow).

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Figure 5:

A 49-year old female with history of shortness of breath and left ventricular hypertrophy but no hypertension or aortic stenosis. Cardiac magnetic resonance steady-state free precession still frame 4chamber view showing symmetrical hypertrophy (arrow).

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LGE was present in 75.7% (n = 56) of the patients [Figures 6 and 7] and most common site was septum plus LV free wall (32.1%, n = 18), followed by apical site (17.8%, n = 10). Most common pattern of LGE was patchy which was present in 73.2% (n = 41).

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Figure 6:

A 71-year old male with history of syncope. Cardiac magnetic resonance late gadolinium image showing apical hyper-enhancement in mid ventricular hypertrophy variant (arrow).

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Figure 7:

A 50-year old male with history of palpitation and syncope. (a) Cardiac magnetic resonance late gadolinium image 2chamber view showing hyper-enhancement in the anterior wall (arrow). (b) Cardiac magnetic resonance late gadolinium image short axis view showing hyper-enhancement in the anterior wall and adjacent septum (arrow).

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Patients were divided into two groups on the basis of presence or absence of LGE [Table 3]. There was no statistically significant difference between two groups on basis of age and gender. However, patients with LGE were more likely to have systolic dysfunction (P = 0.018) and mean EF was also found to be lower in patients with LGE (P < 0.001). Maximal LV wall thickness and mean LV mass was also greater in patients with LGE (P = 0.001 and 0.016) compared to those without LGE.

Follow-up was available in all patients and mean follow-up duration was 39.6 + 27.3 months. Major adverse cardiac events (MACE) (Death, heart failure, VT/VF) were observed in 40.5% (30/74) of the study population [Table 4].

Patients were divided into two groups on the basis of presence or absence of MACE [Table 5]. The presence of LGE and RV involvement was found to have a statistically significant association with MACE. In multivariable analysis, only LGE was significantly associated with MACE (odd ratio: 4.65; 95% CI: 1.21–17.88).

DISCUSSION

This is the first study of its kind from this part of the world, describing the patterns of LV hypertrophy and LGE in patients with HCM on CMR, and looking at their prognostic significance. This will highlight the importance of CMR in the diagnosis and management of HCM in our population.

CMR plays a pivotal role in the diagnosis and risk stratification of patients with HCM. Due to high resolution, CMR determines the LV wall thickness accurately, compared to echocardiography. There are multiple morphological variants of HCM which are easily recognized by CMR. Asymmetrical septal hypertrophy was the most common morphologic presentation of HCM in our series. In this variant hypertrophy predominantly involves the septum.^[4] Septal and anterior wall hypertrophy was the next common pattern of hypertrophy. In this variant hypertrophy predominantly involves the basal anterior wall and contiguous portion of the anterior inter-ventricular septum.^[4]

These findings are consistent with the findings in the literature, asymmetric HCM or septal HCM is the most common morphologic presentation accounting for about two thirds of the spectrum.^[4,5]

In mid ventricular hypertrophy variant, the hypertrophy predominantly involves the mid segments of the left ventricle and may result in mid ventricular obstruction.^[6,7] It may be associated with the formation of an apical aneurysm. This variant was seen in small number of patients in our study.

In apical variant, the hypertrophy predominantly involves the apical segments. Diagnostic criteria for apical HCM include an absolute apical wall thickness of >15 mm or a ratio comparing apical LV and basal LV wall thicknesses of ≥1.3–1.5.^[8,9] Apical HCM also called “Yamaguchi syndrome” is a relatively uncommon form of HCM. This variant is more frequent in the Japanese population. In this condition, there is obliteration of LV cavity at the apex, giving a characteristic spade-like configuration. In our study, apical variant was found in 6.8% (n = 5), which is a little higher than the figures reported from western countries (~2%) but significantly lower than that of Japan (~25%).^[4,8]

In the variant with symmetrical hypertrophy, the hypertrophy involves the ventricular wall symmetrically with no regional preferences. LV cavity dimensions are reduced in a concentric fashion.^[7,10] This entity should be evaluated closely to differentiate it from other causes of symmetric LV thickening.

On contrast enhanced CMR, areas of LGE can also be detected, which are considered to represent areas of fibrosis. Identification of fibrosis by LGE technique has prognostic significance in predicting adverse clinical outcomes. In our study, LGE was present in 75.7% cases, which is little higher than the figures reported in the literature. LGE was reported in 55% by Maron et al.,^[11] 42% by Chan et al.,^[12] 63% by O’Hanlon et al.,^[13] 68% by Lyon et al.,^[14] 66.2% by Ismail et al.,^[15] and 68.9% by Klopotowski et al.^[16] There are only few studies on the Asian population and, to the best of our knowledge, no data are available on LGE in sub-continental South Asian HCM population. LGE was observed in 73% of study population in Japan by Hen et al.^[17] Choi et al.^[18] reported a significantly higher detection of LGE in 91.5% of study population in South Korea. The pooled prevalence of LGE was found to be 60% in a meta-analysis of four studies which evaluated 1063 patients.^[19] The variable prevalence can be explained by the different study population, study designs, inter-observer variability, and LGE detection methods.

Most common location for LGE in our study was septum and LV free wall, which was also observed in studies by Maron et al. and Olivotto et al.^[11,20] However, apex was the most common site in a study by Hen et al. in Japanese cohort.^[17]

Severity of hypertrophy showed statistically significant association with the presence of LGE in our study, which is in agreement with the findings of studies by Ismail et al. and others.^[11,15,20] Our study found a statistically significant association between LGE and LVOT obstruction, in contrast no such association was found by Maron et al.^[11] Association of LGE with systolic dysfunction and lower EF was reported in the studies,^[11,14,15] and similar findings were observed in our study.

A high rate of MACE was observed in our study population, which is similar to what Songsirisuk et al.^[21] observed. Cardiovascular complications were reported in 47% of Chinese HOCM population by Ho et al.^[22] and in 35.6% by Lee et al.^[23] in Taiwan. However, in contrast lower rate was reported by studies in Europe and USA.^[13,24,25] These differences are probably due to the heterogeneous population, variable definition of MACE, rate of ICD insertion, and health-care resources. MACE were more common in patients with LGE, presence of LGE has been found to increase the risk of SCD, cardiovascular complications, and increase in all-cause mortality.^[26,27]

The prevalence of RV involvement is 16.2% in our study which is similar to 18% reported in the literature.^[4,7] This typically involves the mid-to-apical portion of the RV. RV involvement was also found to be associated with cardiovascular complications in our study and this was in agreement with various other studies,^[28,29] in which RV involvement was associated with increased risk of sudden death and ventricular arrhythmias.

LVOT obstruction was present in 28.4% of the patients in our study, which is comparable to that found in the studies done by Songsirisuk et al. (24%) and Maron et al. (25%).^[21,30] However, in a study done by Lee et al. on Taiwanese population, LVOT obstruction was demonstrated in a much higher percentage (48.1%) of HCM patients.^[23]

LVOT obstruction was also associated with MACE^[22] and was a strong, independent predictor of progression to severe symptoms of heart failure and death^[30] in studies done by Ho et al. and Maron et al., respectively, which was not the case in our study group.

CONCLUSION

Asymmetrical septal hypertrophy was the most common pattern of hypertrophy, followed by septal and anterior wall hypertrophy. LGE was present in three fourth of the study population, with patchy enhancement being the most common pattern. Patients with LGE were more likely to have systolic dysfunction and mean EF was found to be lower in patients with LGE. MACE (Death, heart Failure, and VT/VF) were observed in less than half of the patients. The presence of LGE and RV involvement was found to have statistically significant association with MACE.

Despite the limitations of this study, the presence of LGE seems to be a promising additional risk marker in predicting outcome in HCM patients, in this region too. After the availability of this local data, there should be no hesitancy in early use of CMR for diagnosis and risk stratification of patients with HCM in our population.