The main goal of our study was to compare the exercise-induced physiological adaptation of the heart to the pathological hemodynamic changes induced by pressure overload in hypertensive patients using LV HDF derived from feature-tracking CMR. We had three primary objectives: 1. To provide the range of normal values of HDF in athletes; 2. To compare the HDF in athletes with those in patients with uncomplicated hypertension; and 3. To compare the HDF in endurance vs strength athletes.
The results of the present study provide reference values for athletes, not only for the entire heart beat but also for single time intervals corresponding to the different phases of the cardiac cycle. In addition, HDF analysis was able to provide insights into the different hemodynamic changes induced by physiological physical training compared to a pathological model of increased LV afterload due to hypertension. Finally, when comparing the different types of training, strength athletes had shorter duration of the systolic impulse and higher HDF of the early LV filling, but no changes in the hemodynamic work.
We employed feature-tracking CMR imaging to measure non-invasively the IVPG which has a fundamental role in cardiac adaptation. HDF analysis, which corresponds to the global value of IVPG integrated over the ventricular volume, can identify the hemodynamic pattern associated with adaptation to different pressure overload at an earlier stage compared to LVEF and deformation analysis, and potentially predict the onset of cardiac remodelling. While previous methods for HDF analysis were hampered by low feasibility [12], a new mathematical formulation has shown that the same information can also be obtained from the endocardial motion and the average flow across the mitral valve and the outflow tract [7].
HDF analysis has been already applied in several studies, using either CMR or echocardiography, including normal subjects [13–15], athletes [16], patients with different types of pathologies (such as heart failure [17–23], cardiac resynchronization therapy [24, 25], post-aortic coarctation [26]), and for the assessment of diastolic dysfunction [27]. However, as for most of the new techniques, standardisation of HDF measurements is still lacking, and different parameters have been reported in different studies. We believe that a detailed analysis of HDF during the phases of the cardiac cycle would provide insights into the complex mechanisms of cardiac function and characterise in detail the pathophysiological patterns in different cardiac adaptive models. The analysis of the HDF curves throughout the entire heart beat integrates in a single value all the components of the different phases of a cardiac cycle, and is not able to resolve the individual component. In fact, the results will include the mathematical sum of all the events (positive and negative directions) during the cardiac cycle, and cannot distinguish the HDF behaviour during a specific time interval. To overcome this limitation, we detected early changes in blood flow acceleration from the dV/dt curve and identified the time limits of all the phases of the cardiac cycle, including for example the elastic rebound and the suction period, which allows to quantify and compare the hemodynamic work of each phases of the cardiac cycle.
There is scanty data on HDF in athletes. Arvidsson et al. applied 4D flow magnetic resonance imaging to 14 elite athletes and 25 healthy volunteers [16]. Apart from the different methodology applied, they considered volume-normalised RMS force during systole, early, and late diastole. When compared to normal volunteers, they found no differences between controls and athletes. Preliminary data by Filomena et al in mixed athletes [28] are consistent with our findings. However, they analysed HDF only for the entire cardiac cycle, the systolic phase, and the diastolic phase, while analysis of the different phases of the cardiac cycle was not considered.
The results from our study provide significant insights into the LV hemodynamics in athletes. When we analysed the entire cardiac cycle, longitudinal HDF was higher in athletes compared to hypertensive patients, while the transverse HDF, L-S/A-B ratio and the impulse angle were similar between the two groups (see Table 3). This indicates that athletes and hypertensive patients have the same (normal) orientation of the HDF, albeit with higher apex-to-base oriented IVPG in athletes. Analysis of the HDF curves during the different phases of the cardiac cycle indicates that athletes have a steeper slope of the systolic ejection, and higher peak/higher hemodynamic work during the first phase of systole. These data suggest the development of higher pressure gradients in a short period of time in athletes compared to hypertensive patients. In terms of diastolic function, compared to hypertensive patients, athletes had a less negative AUC values (-0·31 vs -0·44, respectively; p = 0·011) and a shorter duration of the elastic rebound (51·6 vs 70·6 ms, respectively; p < 0·001). This can be explained by the stiffness of the left ventricle in hypertensive patients which needs higher work and longer time to release the elastic energy stored by the preceding systolic deformation. In addition, this method allowed us to evaluate the suction that plays a major role in LV filling. Our results indicate that in hypertensive patients the suction mechanism is lost as demonstrated by the abnormal direction (apex-to-base) of the HDF during this phase. This might be related to an abnormal rate of untwisting in early diastole, a mechanism which has been shown to contribute to the occurrence of diastolic suction. Finally, while the early LV filling is similar, the atrial thrust is significantly higher in hypertensive patients than in athletes (-0·31 vs -0·05, respectively; p < 0·001), indicating the importance of the active LV filling in hypertensive patients.
Comparative analysis between endurance and strength athletes found no significant difference in HDF values along the entire heart beat. Analysis of the single phases of the cardiac cycle showed that strength athletes have a shorter duration of the first phase of the systole and of the systolic impulse. These findings can be explained by the different modalities of generation of IVPG in the two types of exercise, and suggest that strength athletes need less time to reach the systolic peak and generate the same level of hemodynamic work. Additionally, the early filling of the left ventricle was lower in endurance athletes compared to strength athletes. This finding could be explained by the higher LVMi and LVEDVi in endurance athletes, which may affect the LV untwisting and filling.
Study limitations
In our study population, 23% of the hypertensive patients had LVMi higher than the upper normal limits reported by Kawel-Boehm et al. [29]. The relatively low number of hypertensive patients with significant increase in LV mass can be explained by the exclusion of patients with hypertension-related complications, and is in line with the prevalence of LV hypertrophy reported in previous study [30]. The CMR protocol did not include the use of gadolinium contrast medium which prevents the assessment of myocardial fibrosis. In this regard, further studies might address the relation between late gadolinium enhancement and the development of abnormal IVPG.