Discussion
The goal of our study was to investigate the effects of increased
afterload on ventricular function using STE analysis in rTOF patients
requiring TPVR. We found that increasing RVSP, particularly RVSP> 75% systemic pressure, was associated with worse
RV GLS despite no significant association with RVEF. Our data also
suggests that higher RVSP, specifically > 75%
systemic, prior to TPVR did not appear to show any improvement in the
average RV GLS within 24 hours post or within
18 months post TPVR.
Increased ventricular afterload results in increased myocardial wall
stress and decreased velocity of fiber shortening. Compensatory
ventricular hypertrophy and increased wall thickness reduces myocardial
wall stress and maintains cardiac output. Right ventricular hypertrophy
also decreases the compliance of the RV and may mitigate the degree of
pulmonary regurgitation, leading to the belief that leaving some degree
of pulmonary stenosis may be beneficial in rTOF patients that typically
suffer from “free” pulmonary insufficiency[3]. However, recent
literature from large multicenter trials has shown that there may be
pathological degrees of right ventricular hypertrophy, with increased RV
mass/volume ratio a risk factor for major adverse cardiac events [4]
. Our study shows that RV GLS is worse in patients with higher RVSP
irrespective of age, which may be an early marker of myocardial
dysfunction. This was also supported by the association between elevated
RVEDP and worse RV GLS.
Though EF remains a well-established marker of ventricular function, we
did not find a similar association with elevated RVSP. Our study
suggests that strain is a more sensitive marker for ventricular
dysfunction, which may show regional myocardial change before a global
decline in EF, as seen in many other patient populations[15, 16,
26]. It also suggests that increased afterload can have a detrimental
effect on RV function and may be a marker for adverse RV remodeling,
which could be mitigated if patients undergo earlier TPVR at lower RVSP.
As noted above, higher RV mass/volume ratio was seen in patients who had
more stenosis on their pre-implantation catheterization, which is a
marker of hypertrophy and has been shown to be an independent risk
factor for ventricular tachycardia and death. Freedom from events in
this population was less with concomitant risk factors, including
ventricular dysfunction and older age[4]. With increasing afterload,
hypertrophy worsens over time in rTOF patients and could place them at
increased risk of poor clinical outcomes in mixed pulmonary valve
disease with predominant afterload.
There are several limitations to this study. The retrospective cohort
nature of our study has data limitations, including missing data. Though
we present a sizeable number of patients with mixed pulmonary valve
disease who underwent TPVR, some patients were excluded due to
poor quality echocardiograms.
Older patients often have poor acoustic windows, which make fully
characterizing the RV endocardium challenging. For this reason, we also
limited our strain analysis to just GLS; as opposed to circumferential
or radial strain. Arrhythmia and bundle branch blocks, which are common
in rTOF patients, can also create challenges when analyzing strain. The
amount of pulmonary regurgitation varied in our population; however, we
were not able to assess varying degrees of regurgitation and stenosis in
distinct groups longitudinally. Also, due to the referral pattern of
patients to our institution for TPVR, patients did not undergo a repeat
CMR to evaluate the effect of valve implantation on volumetry and
function within the follow-up evaluation period. Prospective
multi-center studies with a long-term follow-up time are needed with
myocardial strain by STE with validation by CMR strain prior to changing
clinical practice. Finally, we have included many analyses presented at
their nominal values and not adjusted for multiplicity. As such the
results should be interpreted as exploratory.
Tables:
Table 1. Demographic Data