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