The main findings of the present analysis can be summarized as follows:
The staging classification of AS-related cardiac changes, derived from randomized trial, maintains its prognostic performance in real-world TAVI patients;
TAVI triggers an early reversal of cardiac dysfunction, mainly driven by the amelioration of LV diastolic and RV function;
Nevertheless, the extent of extra- aortic valve cardiac damage at baseline significantly affects survival at 1-year after the procedure.
The identification of clinical and anatomic factors that affect clinical outcomes of patients with severe AS represents an important unmet need. Several scoring systems that account for baseline features and measures of frailty have been proposed for counselling AS patients.(17, 18) However, their use in clinical practice is challenged by the lack or limited availability of all the required variables. In this context, the staging classification of cardiac damage by Généreaux et al features the unique advantage to be widely applicable as it is based on echocardiographic parameters that are routinely evaluated in patients with severe AS. This system was formulated by leveraging on data of 1,661 patients from the PARTNER 2 trial and proved a powerful predictor of mortality at 1-year after aortic valve intervention (either surgical or transcatheter).(7) In our study, including real-world patients, the system retains its prognostic ability as a greater extent of cardiac damage was associated with increased risk of all-cause mortality after TAVI. These findings are in line with prior studies that applied the staging classification system in larger populations. In a retrospective analysis of 1,189 symptomatic severe AS patients, stage of cardiac injury was independently associated with all-cause mortality and combined endpoint of all-cause mortality, stroke, and cardiac-related hospitalization.(19) Among asymptomatic patients with moderate to severe AS, the staging was significantly associated with excess mortality in multivariable analysis adjusted for aortic valve replacement as a time-dependent variable (hazard ratio: 1.31 per each increase in stage; 95% CI: 1.06 to 1.61; p = 0.01) and proved incremental value over other traditional risk markers.(20) Another study applied the staging system to TAVI patients and found a graded association between cardiac damage and all-cause mortality.(21)
However, our analysis is the first to assess the impact of TAVI on the extent of extra-aortic valve cardiac damage. We found that the procedure triggers an early (within 30-day) re-classification of the stages owing to significant changes in measures of LV diastolic and RV function. LV hypertrophy and collagen abnormalities develop in patients with severe AS and impair diastolic function. Objective evidence of variable degree of LV diastolic dysfunction, indeed, has been reported in up to two-thirds of patients undergoing TAVI.(22) Similarly, RV dysfunction has been documented in up to 1 in 4 patients with severe AS as consequence of transmission of elevated left-sided pressures back through the pulmonary vascular system. The suppression of pressure overload by TAVI ameliorates LV filling pressures (E/e’ ratio), as suggested by the concomitant reduction of left atrial volume. Along the same line, a trend towards normalization of TAPSE may occur after TAVI (23, 24) as well as a reduction of pulmonary hypertension.(25) Nevertheless, these changes do not improve survival after TAVI as baseline conditions predominate in determining prognosis at 1-year. Consistently, we observed an overall improvement of myocardial function suggested by changes in LV-GLS after TAVI with no relevant impact on mortality at 1-year.
The main clinical implication of the results of our study is the need for rethinking the optimal timing of intervention in patients with AS. Multiple lines of evidence indicate that the greater is the extent of cardiac damage before TAVI, the higher is the probability of worse outcomes after the procedure. Moreover, irreversible structural cardiac changes induced by longstanding AS neutralize the beneficial impact of TAVI on some functional parameters. In this perspective, anticipating the intervention might have the potential advantage to obtain the full reversibility of cardiac function and improve survival at a greater extent.
Our study has several limitations. It is a retrospective analysis of data collected at a single center, thus subject to inherent flaws related to that design. A comprehensive assessment of echocardiographic parameters after TAVI was not performed in the overall population affecting the completeness of our observations. Parameters used for staging the extent of cardiac damage are those obtained in the context of the routine echocardiogram of TAVI patients and potentially subject to measurement errors and variability. We did not assess the potential modifying effect of paravalvular aortic regurgitation on echocardiographic and clinical outcomes after TAVI.
In conclusion, the staging classification confirms its utility as additive clinical tool to enhance risk stratification and therapeutic decision making in patients with AS. TAVI might reverse functional cardiac changes associated with AS; however, survival at medium-term is mainly related to the baseline grade of extent of cardiac damage. Further and larger studies are needed to assess the value of the staging classification in the post-procedural setting.