Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiovascular disease, with a prevalence of 0.2% in the general population. It has a higher prevalence (0.5%) when both clinical and genetic diagnoses are taken into account [1‐3]. HCM has been regarded as having a poor prognosis with limited management options. During the last 2 decades, important advances in contemporary management strategies have greatly improved the life expectancy and quality of patients with HCM [3‐5].

However, some recent studies have suggested that other cardiac or non-cardiac comorbidities might have a greater impact on survival than long-standing HCM itself [6, 7]. For example, some studies have shown that coronary artery disease (CAD) is associated with an increase in poor prognosis in patients with HCM [8, 9]. The serum concentration of high-sensitivity cardiac troponin T (hs-cTnT), a sensitive and specific marker of myocardial injury, is also reportedly effective in predicting adverse outcomes in patients with HCM [10, 11]. In general, CAD can cause a decrease in coronary blood flow to different degrees, and in patients who have HCM without myocardial infarction, an elevated hs-cTnT concentration may indicate microvascular dysfunction [10, 12]. These parameters might represent the total ischemic burden of the myocardium in HCM, which is considered to be associated with poor outcomes. However, whether evaluations of CAD and hs-cTnT might supplement each other and thus become more reliable prognostic markers in patients with HCM remains unclear. The present study was therefore performed to examine the efficiency of combined evaluation of these two markers for prediction of adverse events in patients with HCM.

We assessed the usefulness of combined evaluation of both CAD and hs-cTnT for prediction of MACEs in patients with HCM. We found that combined evaluation of these two markers is a more reliable predictor of MACEs than evaluation of a single marker. Thus, our findings might be of value to classify the prognosis and guide risk management in patients with HCM.

Many studies have shown that patients with HCM have a relatively benign prognosis and a mortality rate similar to that in the general population [3‐5]; however, other comorbidities might pose a greater threat to survival than long-standing HCM itself [6, 7, 9]. As an important comorbidity, CAD can predict future adverse outcomes in patients with HCM. Sorajja et al. [8] showed that patients with concomitant severe CAD had an increased risk of death. In a recent study, Shin et al. [9] reported that severe CAD served as an independent predictor of adverse cardiovascular events in patients with HCM, and the incidence of clear CAD-related mortality or morbidity was about 25% among the events. In our study, the clinical course was significantly worse in the CAD group, and the incidence of clear CAD-related MACEs was about 20.8% among the events. Therefore, the evaluation of CAD may be important in patients with HCM. Moreover, elevated troponin is commonly seen in patients with HCM, and an elevated hs-cTnT above a cut-off point of 14 ng/l is seen in 26% to 54% of patients with HCM [11]. The hs-cTnT concentration has been positively related to the LV wall thickness [10, 16‐18], hemodynamic parameters [10, 16, 17], clinical symptoms [1, 10, 11, 19], and outcomes [1, 10, 11, 19] in patients with HCM. Furthermore, the risk of adverse cardiovascular events seems to be greater with increased degrees of abnormality in the hs-cTnT concentration. Our study also showed similar results; therefore, hs-cTnT is expected to be useful in the clinical evaluation of patients with HCM. Although our multivariate analysis showed that statistical significance was not achieved, our findings suggested that both CAD and elevated hs-cTnT tended to be positively associated with MACEs. We believe that this might have been caused by the relatively small sample and that our results could be improved by a larger sample. Notably, however, the combined evaluation of the two markers significantly improved the predictive values. This combined evaluation achieved statistical significance in the same sample and therefore indicates the clinical usefulness of combined evaluation.

In the present study, combined evaluation of both CAD and hs-cTnT had better predictive value than evaluation of a single marker. When patients with HCM have CAD, the coronary blood flow might decrease to different degrees, which could cause MACEs. Furthermore, patients with HCM who develop CAD usually have more cardiovascular risk factors [8, 20]. From this viewpoint, our study supports previous findings. These cardiovascular risk factors can exacerbate the structural abnormalities and inherent endothelial dysfunction in patients with HCM [8, 21], further increasing the detrimental impact on the prognosis. However, the mechanisms underlying the release of hs-cTnT in patients with HCM remain unclear. It is speculated that the increase may be caused by relative myocardial ischemia resulting from an imbalance between inappropriate hypertrophy of the myocardium and insufficient coronary arterial supply [10, 12]. In this respect, the present study proposes microvascular dysfunction as an important explanation [12]. Microvascular dysfunction associated with elevated hs-cTnT can result in myocyte injury and subsequent fibrosis in HCM, leading to poor outcomes [10, 12]. Given the increased myocardial mass and high myocardial oxygen demand, patients with microvascular dysfunction might be particularly susceptible to the additional ischemic burden of CAD [22], further increasing the incidence of adverse outcomes. As mentioned above, epicardial CAD might respect a diminished coronary flow and a cluster of cardiovascular risk factors, whereas elevated hs-cTnT could respect myocardial injury and microvascular dysfunction; these might represent the total ischemic burden of the myocardium. Therefore, combined evaluation of both CAD and hs-cTnT should have greater prediction ability than evaluation of a single marker. Notably, performing coronary artery imaging in patients with HCM who have both elevated hs-cTnT and risk factors for CAD is taken for granted. Therefore, we should pay more attention to patients with either elevated hs-cTnT or risk factors for CAD, especially asymptomatic patients; such patients may need further coronary artery imaging.

This study has several limitations. First, this was a single-center retrospective clinical study and therefore may have certain inherent biases. We could only use the patients’ existing data. In total, 321 patients were excluded because of a lack of coronary artery imaging and hs-cTnT data, which may represent a selection bias. Although this was a specially selected group of patients, it still indicates the risk of CAD combination for this type of patient. Additionally, some patients’ baseline data excluded renal function parameters. However, renal insufficiency was not diagnosed in the medical records; therefore, we can partially rule out renal insufficiency as a cause of the rise in troponin. These limitations warrant prospective studies. Second, coronary imaging and hs-cTnT measurement should ideally have been performed during a steady state. In our study, 52 (32.1%) patients had NYHA class III/IV heart failure, which may suggest the acute phase of disease. Therefore, larger prospective studies are needed to confirm and extend the present findings. Third, the number of MACEs was so small (n = 24) that the subanalysis and grouping analysis may have limited the statistical value; however, these analyses still provided useful findings. Although the multivariate analysis showed that statistical significance was not achieved, our findings suggest that both CAD and elevated hs-cTnT tended to be positively associated with MACEs. We believe that this could be improved by a larger sample. Because of the small number of events, the role of combined evaluation of CAD and hs-cTnT in specific subgroups of patients with HCM remains to be further evaluated. Fourth, not all patients agreed to undergo coronary angiography, and 33 (20.4%) patients underwent coronary CT angiography; this might suggest that the study population was somewhat heterogeneous. However, coronary CT angiography has high negative and positive predictive values in patients with HCM [22], and the use of coronary CT angiography should be acceptable. Fifth, because the severity of CAD was assessed by coronary angiography or coronary CT angiography without intravascular ultrasound or optical coherence tomography, the specific causes of stenosis cannot be determined. However, the performance of intravascular ultrasound and optical coherence tomography for all patients was not feasible for pragmatic and logistical reasons. Finally, severe CAD usually requires intervention and has a very poor prognosis. Therefore, the combination of patients with severe CAD and mild to moderate CAD into a single group may have caused bias. However, the additional analysis indicated similar results, further supporting the main analysis.

Combined evaluation of both CAD and hs-cTnT could be a more reliable predictor of MACEs than evaluation of a single marker in patients with HCM. The present study findings may be of value to classify the prognosis and guide risk management in patients with HCM. Larger studies are needed to confirm these findings.