DISCUSSION

This study identified four variables, i.e., LV global longitudinal strain, LA volume index, LV mass index and septal TDI E/e’ ratio, as the echocardiographic criteria to distinguish HCM from other forms of LVH.

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LVH can occur as physiological adaptations to intense physical training (i.e., athlete’s heart) or as pathological hypertrophy associated with HTN, HCM, and infiltrative disease. The LVH in athletes may overlap with pathological hypertrophy such as those seen in HCM or HTN-LVH. However, compared to HTN-LVH, LVH associated with HCM is a more worrisome cardiovascular disease that could be clinically silent but could predispose individuals to sudden deaths. Unfortunately, HCM is the single most common disease causally linked to athletic field deaths, accounting for about one-third of sudden deaths among young competitive athletes.^{2, 3, 4} Although certain strategies had been outlined to prevent sudden cardiac deaths in elite athletes, the utility of echocardiography in HCM screening is not mandated in competitive sports.⁶ Furthermore, the detection rate of HCM with history and physical examination screening in the athletic population appears to be relatively low.^{3, 18, 19, 20}

The echocardiography criteria and cutoff values described in previous studies for the detection of HCM were derived from Caucasians and African/American athlete populations and therefore might not be applicable in Asian athlete population, which is characterized by different patterns of LV remodeling.^{12, 13} In the present analysis, we took advantage of studying distinct populations of highly trained athletes; untrained patients with LVH associated with HTN only; untrained patients with HCM whose diagnosis were supported by cardiac magnetic resonance imaging (MRI), who were symptomatic, and presented with pathological outcomes such as sudden cardiac arrests, stroke, requiring cardiopulmonary resuscitation (CPR) and ICU admission, or ICD implantations; and sedentary healthy individuals as controls, matched for sex.

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MORPHOLOGICAL COMPARISON BETWEEN STUDY POPULATION AND WESTERN POPULATION

Similar to previous studies comparing elite athletes with sedentary patients with HCM,¹² the athletes in our cohort showed homogenous distribution of wall thickness, with absolute differences of 0.1 cm between the thickest (septal wall) and thinnest (LV posterior wall) segments. These observations support the principle that physiologic LV remodeling is characterized by a symmetric increase in LV wall thickness as a consequence of the hemodynamic volume overload associated with exercise.^{7, 8} In contrary, the asymmetric and heterogeneous patterns of LVH in HCM represent the phenotypic expression of genetic disease.

Previous studies reported LV cavity dimension as a good discriminator between athlete’s heart and morphologically mild HCM.^{21, 22, 23} A recent report suggested LV cavity dimension (end diastolic) to be a particularly good discriminator, favoring physiological LVH over HCM with both sensitivity and specificity of 100%.¹² In our study cohort, however, no significant differences in LV cavity dimension were identified among athletes, patients with HTN-LVH, and patients with HCM.

In the ROC curve analysis for distinguishing HCM from other variants of LVH, rather than wall thickness, we found LV mass indexed to BSA to be a better discriminator between athlete’s heart and HCM.

A recent report identified the cutoff value of LA size according to the basic measurement of the LA anteroposterior diameter.¹² Although very commonly used in routine clinical practice, the LA anteroposterior diameter is still inadequate for assessing morphologic changes in the LA associated with athletic conditioning.²⁰ Our study assessed and identified the cutoff value for LA size by measuring LA volume according to modified Simpson’s biplane rule and indexing it to the BSA. An LA volume index of 34.7 ml/m² had lower sensitivity compared to LA anteroposterior diameter as suggested in previous report,¹² but the discriminatory ability was better with higher area under the curve, and the false-positive results were also lower.

 

FUNCTIONAL COMPARISON WITH PREVIOUS STUDIES OF DOPPLER-DERIVED, TISSUE DOPPLER, AND 2D SPECKLE-TRACKING ECHOCARDIOGRAPHY PARAMETERS

Among echocardiographic parameters of LV function, we found only two parameters, namely, LV global longitudinal strain and septal TDI E/e’ ratio, to be better discriminators between athlete’s heart and HCM compared to previous studies involving Caucasian and African/American populations.¹³

In accordance with previous literatures,^{24, 25} we observed significantly lower LV global longitudinal strain in patients with HCM than in patients with HTN-LVH, athletes, and HC. Although Alfonso et al.²⁴ noted mitral annular e’ velocity to be superior to LV global longitudinal strain in differentiating LVH from HCM, our analysis, however, revealed that LV global longitudinal strain <-15.4% favoring the diagnosis of HCM offers the best discriminatory ability among all other echocardiography parameters.

In addition, in contrast to previous reports,^{12, 21, 24} the ROC curve analysis in our study did not suggest TDI mitral annular e’ velocity to be a good discriminator. However, our study demonstrated higher area under the curve and better compromise between sensitivity and specificity when discriminating HCM from other variants of LVH with similar cutoff value identified for septal E/e’ ratio.²¹

 

CLINICAL IMPLICATIONS

Sudden cardiac death in an apparently young and healthy athlete is a tragic event. Often, in Europe and America, tragic deaths involving elite athletes are highly publicized and generate considerable attention in the local community, which may commit significant financial resources to prevent future events.¹⁹ Over the years, experts in sports cardiology have worked to quantify the incidence of sudden cardiac deaths in athletes, identify risk factors, and develop pre-participation screening tools. Comparatively, in Asia, the incidence of sudden cardiac deaths in athletes has not been widely reported. The pre-participation screening strategies were adapted from recommendations by multiple societies based on the data which were derived from the European and American athletic populations.^{5, 26,27, 28, 29}

Accurate identification of HCM in athletes has relevant clinical implications, because this disease is one of the most common causes of deaths on athletic field and usually represents the basis for disqualification from competitive and professional sports.^{2, 23, 30, 31, 32} Diagnosis of HCM in young competitive athletes may be clinically challenging when the extent of LVH is mild and mimic athlete’s heart. We recognized that cardiac MRI is the gold standard to confirm the diagnosis of HCM; unfortunately, it is not made available easily, not to mention its associated cost. Hence, we need a cost-effective and easily available diagnostic tool like echocardiography for screening HCM. In this study, we have identified a few variables that make HCM significantly different from all other variants of LVH. The cutoff values were identified for these variables using ROC curve analysis.

Our results have significant practical implications; to our knowledge, our study was the first of its kind in identifying echocardiographic criteria for detection of HCM in elite athletes in a South-East Asian population. Although not an absolute screening method and further investigations remain to be done with focus on Asian athletic populations, the echocardiographic screening using the four criteria is recommended to be the pre-participation evaluation tool prior to competitions in athletes.

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LIMITATIONS

The authors recognized some limitations in this study. First, the relatively small number of athletes with LVH, patients with HTN- LVH, and patients with HCM may underrepresent the overall spectrum of LVH. In view of the small sample size, only male patients were analyzed. A consistent finding across studies is that male athletes have a 3–5 times higher incidence of sudden cardiac deaths than female athletes.^{33, 34} Second, the echocardiographic findings from our athlete cohort were derived from professional footballers only. It is worth comparing different patterns of LV remodeling among elite athletes from various sports disciplines, such as endurance athletes (e.g., runners, swimmers, cyclists), isometric sports athletes (e.g., weightlifters, bowlers), as well as other combined sports athletes (e.g., hockey players, basketball players, squash players) in future studies. In addition, the participants in all four study subgroups were not age-matched. The athletes in our study were much younger compared to patients with HCM and patients with HTN-LVH. Nevertheless, our study showed that the echocardiographic data were not confounded by age. The echocardiographic criteria described in our study had also demonstrated higher discriminatory ability with a significant cutoff value that distinguishes HCM from other variants of LVH. Finally, the cutoff values described in this study were derived from our local athlete population and therefore might not be directly applicable to other athlete populations, such as Caucasians, African Americans, or other Asians.¹³ In addition, our findings may not be extrapolated to patients with reduced LVEF.

 

CONCLUSIONS

Although future studies on Asian athletic population are warranted, LV mass index, LA volume index, septal TDI E/e’ ratio, and LV global longitudinal strain were found to be the echocardiographic variables with higher accuracy to distinguish HCM. Therefore, incorporation of echocardiography as imaging modality in pre-participation screening should be recommended to elite athletes before any competitive professional sporting events. We propose that athletes with LVH in whom these echocardiographic variables, i.e., LV mass index, LA volume index, septal TDI E/e’ ratio and LV global longitudinal strain, exceed the cutoff values (as found in our population) should undergo comprehensive cardiovascular assessment before undertaking strenuous exercise. This practice would prevent sudden cardiac deaths of young athletes on a playing field.

 

ACKNOWLEDGEMENTS

We would like to thank the Director General of Health Malaysia for his permission to publish this article. We thank the State Football Association of Sarawak for their support in this study. We also acknowledge the support and contribution of nurses and doctors at Klinik Kesihatan Kota Sentosa.

 

FUNDING

This work was supported by research grant from the National Institute of Health, Ministry of Health of Malaysia [grant number NMRR-14-1051-22147]. The sponsor had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report. The sponsor approved the article to be submitted for publication.

 

CONFLICT OF INTEREST

None.

AUTHOR CONTRIBUTIONS

Diana Hui Ping Foo Data curation, Funding acquisition, Investigation, Methodology, Project administration, Writing – original draft
Kai Huat Lam Conceptualization, Investigation, Methodology, Supervision, Writing – review & editing
Mohamad Adam Bin Bujang Formal analysis, Methodology, Validation Andrew Kilung Investigation, Methodology Sally Suriani Ahip Resources
Tiong Kiam Ong Resources, Supervision
Alan Yean Yip Fong Conceptualization, Funding acquisition, Resources, Supervision, Writing – review & editing

All the authors have approved the final version of the manuscript.