This study shows that myocardial fibrosis (detected as LGE on MRI) may influence the development of LVOT gradient during exercise in patients with HCM and normal EF: patients with higher exercise-induced gradients show a lesser degree of myocardial fibrosis and vice versa (). This negative association is more evident in patients with an obstructive form at rest.
Figure 3 Myocardial fibrosis and changes in left ventricular (LV) outflow tract gradient during exercise. (A) Patient with a large amount of myocardial fibrosis and modest increase in LV outflow tract gradient. (B) Patient with a limited amount of fibrosis and (more ...)
In recent years, myocardial fibrosis has been emerging as an important factor in the complex pathophysiology of HCM. It has been suggested that impairment in collagen turnover could be a component of the disease phenotype and that it appears as an early manifestation of sarcomere gene mutations, before the development of overt LV hypertrophy.19
When hypertrophy develops, increasing amounts of interstitial fibrosis can be detected non-invasively by gadolinium-enhanced cardiac MRI.6–8
The exact mechanism leading to fibrosis remains unknown but it has been hypothesised that the main triggers for the fibrotic process include molecular factors at the cellular level (induced by sarcomeric mutations), haemodynamic factors (overall ventricular afterload resulting from the sum of LV outflow obstruction and systolic blood pressure), and ischaemia (mainly related to small intramural coronary vessel disease).8
Myocardial fibrosis in HCM has been associated with the risk of life-threatening arrhythmias and with a wide spectrum of systolic dysfunction, ranging from a mild LV EF reduction to the end-stage phase.9–14
The present study confirmed the association between myocardial fibrosis and contractility, assuming that LV systolic function is one of the major determinants of the LVOT gradient increase during effort. The prevalence of myocardial fibrosis (71%) in our study is comparable with that of the largest published series;12
in most cases, however, LGE was modest and presented a patchy distribution. Our results therefore support the concept of a continuum of haemodynamic effect of myocardial fibrosis on LV function. Large ‘scar-like’ areas of fibrosis are a determinant of the end-stage evolution, lesser degrees of fibrosis are associated with slight EF reduction,14
while even lesser degrees of fibrosis, while not influencing EF at rest, seem to result in a lesser contractility recruitment during exercise, leading to a lower LV outflow gradient. Notably, the effects of myocardial fibrosis were particularly evident among patients with LV outflow gradient already present at rest. Indeed LV contractility is not the only determinant of LV outflow obstruction; excessive length of the anterior mitral leaflet, abnormalities in the subvalvular apparatus and load conditions also play a role.21
In patients with no LV outflow obstruction at rest (related eg, to the large anatomical size of LVOT and/or a non-redundant mitral valve), the increase in contractility could fail to generate a significant LV gradient increase regardless of the amount of myocardial fibrosis.
When interpreting our findings one must consider the low absolute number of patients as well as the fact that the results derived from the analysis of multiple subgroups, even though these were identified with a solid pathophysiological rationale.
The lack of direct haemodynamic measurement of LV pressures limits the pathophysiological interpretation of our data which are essentially based on the behaviour of LV outflow gradient and indexes of ventricular and myocardial function. Also, our study did not include a detailed analysis of the behaviour of LV volumes during exercise and of their correlation with other variables. Indeed, the small absolute values of LV end-systolic volume in this disease during exercise (often below the repeatability threshold) make echocardiography an unreliable technique for this purpose.