In patients with severe aortic stenosis (AS), a reduced left ventricular (LV) ejection fraction (LVEF) is associated with increased mortality after aortic valve replacement (AVR). Both the American and European valve guidelines indicate that LVEF < 50% is a class I indication for AVR, even in the absence of symptoms, although a recent large single-center study suggested that the LVEF cut point should be even higher. Among patients with LVEF < 50%, those with “classic” low-flow, low-gradient (LFLG) AS (as opposed to “paradoxical” LFLG AS) represent a unique clinical challenge. Dobutamine stress echocardiography is recommended to distinguish between truly severe versus pseudosevere AS (to determine whether to perform AVR) and to determine whether there is flow reserve, which has implications for procedural risk and postoperative survival. Even in the absence of flow reserve, however, AVR appears to be associated with improved survival. To date, a limited number of studies performed on this subgroup of patients with AS have demonstrated that medical therapy, a lower mean transvalvular gradient at rest, the lack of flow reserve with dobutamine, multivessel coronary disease, and reduced global longitudinal strain at rest and with dobutamine are associated with increased mortality. Notably, these studies have all focused on the association between left-sided factors and clinical outcomes. Might an evaluation of the right side of the heart be informative to risk-stratify these patients?
Prognostic Value of Right Ventricular Function in Patients without AS
More than three decades ago, studies emerged demonstrating the adverse prognosis associated with right ventricular (RV) dysfunction in patients with congestive heart failure, including increased mortality and reduced exercise capacity. These findings were confirmed in later, larger studies. More recently, RV dysfunction has been associated with increased mortality in patients with heart failure and preserved LVEF.
Does RV Function Risk-Stratify Patients with AS?
Given the prognostic significance of RV dysfunction in patients with non-AS heart failure, attention has turned to evaluating RV function in patients with AS. Emerging studies demonstrate that RV dysfunction occurs in one quarter to one third of patients with severe AS. In a recent analysis of the Placement of Aortic Transcatheter Valves (PARTNER) II inoperable cohort, RV dysfunction was associated with increased mortality after transcatheter AVR in univariate analysis, but not after adjustment for confounders. However, that analysis also highlighted that there are multiple factors to consider on the right side of the heart in addition to RV function. In particular, moderate to severe tricuspid regurgitation, RV dilation, and right atrial enlargement were each associated with increased mortality after transcatheter AVR in unadjusted and adjusted models. Similar findings regarding the adverse impact of tricuspid regurgitation were recently confirmed in patients with LFLG AS.
How one evaluates RV function, though, likely matters. In the PARTNER analysis, RV function was evaluated semiquantitatively and often qualitatively. Use of more quantitative methods, including tricuspid annular plane systolic excursion, tissue Doppler, fractional area change, and longitudinal strain, provides more accurate and sensitive ways to evaluate RV function.
In this context, the report by Cavalcante et al . in this issue of JASE provides new and helpful information regarding the prognostic utility of a quantitative assessment of RV function in the subgroup of patients with LFLG AS. Their primary measurement of RV function was tricuspid annular plane systolic excursion, which is a simple and widely used quantitative measurement. Consistent with American Society of Echocardiography guidelines, tricuspid annular plane systolic excursion < 16 mm was defined as abnormal and observed in 57% of the subjects. This is a higher proportion than observed in prior studies in patients with AS, likely because of their focus on a sicker population with concomitant LV dysfunction. Compared with those with normal RV function, those with RV dysfunction were characterized by an increased prevalence of atrial arrhythmias and diabetes, reduced LV longitudinal systolic strain, worse tricuspid regurgitation, and a trend toward a larger left atrial volume index, but a similar LVEF, Society of Thoracic Surgeons (STS) risk score, and frequency of flow reserve with dobutamine. Additionally, patients with RV dysfunction had lower pulmonary artery pressures than those with normal RV function, which could be due to a lower stroke volume generated by the right ventricle, perhaps related to worse tricuspid regurgitation. Finally, and importantly for this analysis, less than half of the cohort was treated with valve replacement (28% surgical AVR and 17% transcatheter AVR), and patients with RV dysfunction were less commonly treated with valve replacement (35% vs 57%, P = .08).
Although this is a large single-center cohort of patients with LFLG AS, 65 patients (with 30 deaths) is still a relatively small number for an outcomes study. Accordingly, the multivariate models were limited in scope. Nonetheless, RV dysfunction had a consistent adjusted hazard of approximately 3 for all-cause mortality; several different models adjusted for all of the key known confounders, including STS score, type of treatment (valve replacement vs medical therapy), severity of tricuspid regurgitation, LV longitudinal strain, and the presence or absence of flow reserve. Although numbers were small, it is important to note that although RV dysfunction was indicative of increased mortality risk, there appeared to be a survival benefit from valve replacement compared with medical therapy in these patients.
Does RV Function Risk-Stratify Patients with AS?
Given the prognostic significance of RV dysfunction in patients with non-AS heart failure, attention has turned to evaluating RV function in patients with AS. Emerging studies demonstrate that RV dysfunction occurs in one quarter to one third of patients with severe AS. In a recent analysis of the Placement of Aortic Transcatheter Valves (PARTNER) II inoperable cohort, RV dysfunction was associated with increased mortality after transcatheter AVR in univariate analysis, but not after adjustment for confounders. However, that analysis also highlighted that there are multiple factors to consider on the right side of the heart in addition to RV function. In particular, moderate to severe tricuspid regurgitation, RV dilation, and right atrial enlargement were each associated with increased mortality after transcatheter AVR in unadjusted and adjusted models. Similar findings regarding the adverse impact of tricuspid regurgitation were recently confirmed in patients with LFLG AS.
How one evaluates RV function, though, likely matters. In the PARTNER analysis, RV function was evaluated semiquantitatively and often qualitatively. Use of more quantitative methods, including tricuspid annular plane systolic excursion, tissue Doppler, fractional area change, and longitudinal strain, provides more accurate and sensitive ways to evaluate RV function.
In this context, the report by Cavalcante et al . in this issue of JASE provides new and helpful information regarding the prognostic utility of a quantitative assessment of RV function in the subgroup of patients with LFLG AS. Their primary measurement of RV function was tricuspid annular plane systolic excursion, which is a simple and widely used quantitative measurement. Consistent with American Society of Echocardiography guidelines, tricuspid annular plane systolic excursion < 16 mm was defined as abnormal and observed in 57% of the subjects. This is a higher proportion than observed in prior studies in patients with AS, likely because of their focus on a sicker population with concomitant LV dysfunction. Compared with those with normal RV function, those with RV dysfunction were characterized by an increased prevalence of atrial arrhythmias and diabetes, reduced LV longitudinal systolic strain, worse tricuspid regurgitation, and a trend toward a larger left atrial volume index, but a similar LVEF, Society of Thoracic Surgeons (STS) risk score, and frequency of flow reserve with dobutamine. Additionally, patients with RV dysfunction had lower pulmonary artery pressures than those with normal RV function, which could be due to a lower stroke volume generated by the right ventricle, perhaps related to worse tricuspid regurgitation. Finally, and importantly for this analysis, less than half of the cohort was treated with valve replacement (28% surgical AVR and 17% transcatheter AVR), and patients with RV dysfunction were less commonly treated with valve replacement (35% vs 57%, P = .08).
Although this is a large single-center cohort of patients with LFLG AS, 65 patients (with 30 deaths) is still a relatively small number for an outcomes study. Accordingly, the multivariate models were limited in scope. Nonetheless, RV dysfunction had a consistent adjusted hazard of approximately 3 for all-cause mortality; several different models adjusted for all of the key known confounders, including STS score, type of treatment (valve replacement vs medical therapy), severity of tricuspid regurgitation, LV longitudinal strain, and the presence or absence of flow reserve. Although numbers were small, it is important to note that although RV dysfunction was indicative of increased mortality risk, there appeared to be a survival benefit from valve replacement compared with medical therapy in these patients.
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