Our study demonstrated that, in BAV patients, the posterior direction of regurgitant jet may cause LV diastolic dysfunction, even in patients with mild AR. Jet impacting on the anterior mitral leaflet was associated to a significant reduction in circumferential and longitudinal diastolic strain rate and peak diastolic velocity as compared to AR patients with non-impacting jet and controls, with no differences in myocardial systolic strain parameters.
To our knowledge, this is the first study that correlates AR jet direction to LV function using CMR.
Although our study population was mainly composed by young and asymptomatic patients, CMR was able to detect the presence of a subtle and clinically silent ventricular function alteration, represented by impaired diastolic function.
After the systolic contraction and the closure of the aortic valve (proto-diastolic phase), the inversion of the pressure gradient between the left atrium and ventricle and relaxation of the ventricular wall cause the opening of the mitral valve, allowing the rapid filling of the ventricle (rapid isotonic diastole).
When posteriorly directed, the eccentric regurgitant jet may hinder normal anterior mitral leaflet mobility causing a fluttering of the valve leaflet and delayed opening [10], resulting in an impairment of the early filling.
Indeed, in our study, PJ group had a delay in peak filling (increase TTPFR), even there were no differences in terms of PFR among three groups.
In cases of moderate-to-severe chronic AR this mechanism may induce asymmetrical mitral valve (MV) remodeling [9], with enlargement and rarely perforation of the anterior leaflet, causing severe mitral insufficiency [17–19].
Diastolic dysfunction, defined as an increased resistance to filling by the LV [20], can be classified in three grades [21] and can be associated to a simple increase in LV end-diastolic pressure and/or to an elevated mean left atrial pressure (which results in a pulmonary venous hypertension, pulmonary congestion and dyspnea) [21].
In our population, PJ patients had both increased end diastolic and systolic LV volumes as compared to nPJ and controls, whereas there were no differences between nPJ and controls, highlighting how the direction of the jet can affect the ventricular filling volumes, even if the regurgitation is not severe enough to cause volume overload.
The early identification of subclinical diastolic dysfunction in BAV patients with preserved ejection fraction and mild AR may be beneficial for improving their risk stratification and predict long-term outcome.
In fact, diastolic dysfunction represents the first altered parameter in the progressive process that may finally result in HF. It is known that the 5-year mortality rate for individuals with HF, preserved ejection fraction and diastolic dysfunction, ranges between 55 to 74% [22].
Moreover, BAV condition per se leads to a greater incidence of cardiovascular complications as compared to the general population (dilation or dissection of the thoracic aorta, aortic valve stenosis or insufficiency, endocarditis and myocardial ischemia) [22–25]. Furthermore, PJ group showed increased aortic annulus diameters as compared to the other groups, suggesting the possibility of additional pathological mechanisms related to the jet eccentricity and cusps asymmetry.
The use of CMR-FT to evaluate LV diastolic impairment has already been performed in asymptomatic patients with BAV and preserved ejection fraction [14], evidencing an alteration in diastolic strain parameters in BAV subjects as compared to control groups [14]. Other studies revealed that CMR-FT myocardial diastolic strain analysis was able to predict adverse outcomes in patients with hypertrophic cardiomyopathy or atherosclerosis [25, 26]
Finally, the use of 4D Flow imaging technique offered a deeper insight on the hemodynamic consequences on intraventricular flows of different patterns of regurgitation jet.
As explained in in-vitro studies conducted on insufficient aortic valves, the presence of a regurgitation jet generates an anticlockwise intraventricular vortex which hampers LV filling, as the degree of regurgitation increases, interacting with the clockwise vortex coming from the mitral valve [27, 28]. We can assume that this mechanism is even more emphasized by the posterior direction of the regurgitation jet, as opposed to non-posterior, which does not seem to interfere with intraventricular hemodynamics in mild AR (Fig. 4).
Indeed, according to our 4D Flow imaging analysis, in PJ group the AR jet deviates the transmitral inflow from the normal direction towards the inferolateral wall, likely increasing local wall stress and influencing intraventricular vortex formation. Conversely, in nPJ group the transmitral diastolic flow direction was preserved with main orientation parallel to the LV longitudinal axis.
The proper vortices generation seems to have a crucial role in the dynamic balance between rotating blood and myocardial tissue contractile activity. Maladaptive intracardiac vortex dynamics may modulate the progressive remodelling of the left ventricle towards cardiac dysfunction (29).
Further 4D flow imaging studies could offer new perspectives to better understand the effect of aortic valve abnormalities not only on downstream flow (30), but also within the ventricular cavity.
Actually, AR is classified by a combination of clinical signs, LV function and size, and aortic regurgitation degree [29]. However, it is poorly known whether specific features (e.g. valve morphology, regurgitation jet pattern) may promote diastolic dysfunction and LV remodeling, even in mild-to-moderate forms.
In our analysis, the presence of posterior jet was most frequently related to the type I L-R configuration where the conjoined cusp was often responsible for the prolapse causing the posteriorly directed jet (it is not a case that, although our study group was rather small, no type 0 or type I L-N were found in the PJ group).
Moreover, the type I L-R configuration is the most frequent form of BAV phenotype, therefore a posterior jet is also a relatively frequent finding.
Finally, given that the AR recurrence after BAV repair is not rare, surgical planning should consider those phenotypes associated to greater risk of residual posteriorly directed jet.
Another aspect of interest would be the evaluation of jet direction effects on intraventricular hemodynamics, during physical or pharmacological stress. Some studies conducted on BAV athletes with mild AR noticed an increase in LV diameters in BAV as compared to tricuspid aortic valve subjects, but LV volumes were within the normal range [30]. How the hemodynamic adaptation to sport activity can influence regurgitation jet direction and, eventually, intracavitary vortexes formation still needs to be investigated.
Study limitations
Our study could be limited by the relatively small sample size of the population, which did not allow the analysis of correlation with the different bicuspid phenotypes. In addition, the low number of individuals who underwent 4D Flow imaging prevented us to elaborate quantitative comparison analysis on 4D Flow data.
We also recognize that the lack of follow-up data did not allow defining the long-term clinical relevance of these phenomena in terms of valve disease progression, ventricular remodeling and ventricular function deterioration.