Discussion
Although commonly used for predicting adverse cardiovascular events, current risk stratification models for HCM using a combination of clinical and imaging parameters are limited in identifying all patients, mainly as a result of the heterogeneity of the disease.3 12 27 As adverse events may occur in patients with HCM that are considered at low risk, there is a need to identify additional markers.2
CMR is recommended a class IB indication in patients with HCM and interest has emerged to improve risk stratification models using CMR parameters.4 In this context, one focus has been on the cascade of myocardial ischaemic reactions. The presence of relative ischaemia has already shown to influence the prognosis of patients with HCM on either arrhythmic events or HF.8 28 In CMR, myocardial ischaemia and fibrosis can be imaged using contrast agents or using parametric mapping on the basis of magnetic relaxation properties.14 29 In particular, T2* mapping is able to characterise the relaxation of the transverse magnetisation that is influenced by macroscopic (inhomogeneities of the magnetic field) and mesoscopic (structure of the tissue) magnetic field inhomogeneities.14 20 In this context, reduced T2* values have already shown the potential to describe structural alterations suggestive of ischaemic alterations, collagen areas or haemorrhage in cardiac and extracardiac tissues.15 18 21 According to this, histopathological substrates of T2* and a correlation of T2* to flow analyses have been studied.16 17 19 20 30 Recently, reduced T2* values have been described in a group of patients with HCM potentially triggered through relative ischaemia.22 Another explanation for the reduction of T2* values could be that in areas of reduced perfusion, oxymyoglobin and haemoglobin as oxygen suppliers are decreased, whereas deoxymyoglobin and haemoglobin are increased. In contrast to oxygenated proteins, deoxygenated proteins are paramagnetic and reduce local T2* values. However, further studies will have to confirm the potential substrates for a T2* reduction.
In the present study, patients with HCM showed a varying degree of myocardial T2* values, which supports previous studies that showed heterogeneity in myocardial ischaemic reactions.12 Therefore, individual cut-offs to predict arrhythmic events could be chosen according to quartiles. T2* mapping in the present study was not designed to detect myocardial iron overload that can further decrease T2*-values with an impact on the prognosis of patients with thalassemia major. No further division below 23.4 ms was made.31
Only the endpoint of ventricular arrhythmia alone was associated with T2* values in patients with HNCM in univariate analyses. Combining arrhythmic events, there was an association between T2* and arrhythmic events of the whole HCM cohort. None could be detected for HF. Assuming T2* values to be influenced by relative ischaemia, previous studies have already detected an association of abnormal T2 signal as a sign for myocardial damage and arrhythmia.32 33 In general, the results of the additional parameter of fibrosis were in line with previous studies showing an increased risk of events for patients with fibrosis.12 28 34 One should note that fibrosis, which was measured covering the whole heart, stayed the strongest predictor for arrhythmic events in patients with HCM throughout univariate and multivariate analyses. Whole heart coverage using T2* is not recommended in recent guidelines due to susceptibility artefacts at the epicardial borders of the heart.20 As T2* has shown reduced values in patients with HCM and fibrosis, current analyses of the association of T2* with cardiac events in HCM possibly support results for fibrosis without the need for contrast agent, but with less clear results. This is further supported that T2* and fibrosis showed no linear correlation. Therefore, T2* values may be of potential value in cases of doubt or when patients with HCM are not eligible for contrast administration.
Especially patients with HNCM exhibited an association between T2* values and ventricular arrhythmia or a combined endpoint, but only in univariate analyses. Taking conventional risk stratification models that include LV wall thickness and LVOT gradient, those patients would have been graded to be at lower risk.4 However, the overall significance could have been hampered due to low numbers in the subgroups.
Comparing the patients below the third quartile in common risk stratification parameters, one should note that thickened IVS and HOCM occurrence were significantly higher in patients with reduced T2* values. However, T2* values did not show a correlation to thickened IVS, elevated LVMi or age. As a consequence, T2* may potentially identify additional patients with a higher risk of arrhythmia that were considered at low risk for cardiac events using previous risk model estimations.4 35 It should be noted that higher T2* values do not preclude future cardiac events, suggesting further influencing factors that should be taken into account.8
The study was conducted as a retrospective, single-centre study. Therefore, the size of our study population, especially in subanalyses, must be acknowledged as one limitation and was the reason to only perform logistic regression. Prospective multicentre studies using longer follow-up periods and more patients should be used to further evaluate the influence of T2*.
Owing to our study design, patients with ICD or confirmed CAD had to be excluded, thereby potentially introducing some study bias.
Finally, LGE was not further subdivided according to the extent in % of affected LVMi as those data have already been published before.12
Perfusion sequences and parametric T1* mapping with extracellular volume measurements would have been of additional value to quantify relative ischaemia without the use of contrast agents. Nevertheless, LGE remains still one of the gold standards for the detection of fibrosis.