Author + information
- ∗Department of Medicine, Icahn School of Medicine, Department of Cardiology, Mount Sinai Beth Israel, New York, New York
- †Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, Department of CT Surgery, Mount Sinai Beth Israel, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Blase A. Carabello, Icahn School of Medicine, Mt. Sinai Beth Israel, Department of Cardiology, Cardiology, 5th Floor, Baird Hall, 350 East 17th Street, New York, New York 10003.
Transcatheter aortic valve replacement (TAVR) has rapidly become a mainstay in the treatment of high-risk and extremely high-risk patients with aortic stenosis (AS). The procedure improves survival compared with conservative therapy and is equivalent to or even superior to surgical aortic valve replacement (SAVR) in patients at high operative risk (1,2). However, despite the remarkable benefits of TAVR, the design of present TAVR prostheses and the methods of their delivery often lead to post-procedure aortic regurgitation (AR) not usually seen after SAVR. Critically, post-procedure AR is associated with both increased early and late post-TAVR mortality (3–7).
Although the association of AR and increased post-TAVR mortality has been known for some time, the study by Jerez-Valero et al. (8), in this issue of JACC: Cardiovascular Interventions, adds measurably to our understanding of this entity by adding an additional 1,735 patients to our collective data base. They clarify that it is primarily acute, moderate to severe post-TAVR AR that has the most impact on mortality.
Two reasonable types of hypotheses may explain the relationship of AR to TAVR outcome: procedural and hemodynamic. Our procedural hypothesis is that post-TAVR AR is related to both the skills and experience of the operators performing the procedure. In this scenario, operator inexperience affects procedure outcome, and AR is a marker of that inexperience. As such, AR itself is a variable unrelated to outcome but rather a marker of skill sets. In support of this hypothesis are previous data suggesting that even mild AR had an adverse effect on outcome (5,9), an unlikely result of the minimal hemodynamic adversity imposed by mild post-TAVR AR. The current study reduces the plausibility of this hypothesis on 2 counts. First, the operators reporting in this study are highly experienced, and although we do not know the time frame of the incidence of the AR (early or late in their experience), the large number of patients would put the vast majority beyond the operators’ learning curves. Additionally this large study suggests that mild AR does not affect mortality; it seems likely that the negative impact of moderate to severe post-TAVR AR on survival is based on adverse hemodynamics imposed by volume overload.
Acute AR and the Previously Normal Left Ventricle
In chronic AR, left ventricular (LV) eccentric remodeling and hypertrophy compensate for the stroke volume lost to regurgitation, allowing the left ventricle to maintain a nearly normal cardiac output while accommodating the volume overload at tolerable filling pressures (10). This adaptation allows the patient with severe AR to be free of symptoms, even during fairly strenuous activity. However, in acute severe AR, adaptive remodeling has not yet occurred. Thus, forward stroke volume is diminished and rapid LV filling from the AR together with a rapid decrease in aortic pressure causes early equalization of LV and distal diastolic pressures (Figure 1) (11), at which point subendocardial coronary blood flow must cease. The outcome of severe acute AR untreated with aortic valve replacement is poor, almost surely due to these adverse hemodynamics. Importantly, in the current study, it was acute AR, not chronic AR (defined as AR that existed before TAVR), that had negative impact on survival.
Acute AR and the Previously Pressure Overloaded Left Ventricle
Although acute AR after TAVR is rarely as severe as in the patient’s hemodynamics portrayed in Figure 1, it does not have to be to impart serious hemodynamic impairment. Obviously TAVR is performed in patients with severe AS. This long-standing pressure overload results in concentric LV hypertrophy, reducing LV compliance and causing increased LV diastolic pressure for any given LV diastolic volume. The pressure-volume data (Figure 2) obtained by Gaasch et al. (12) are instructive in this regard. By serendipity, pressure-volume data were obtained from a patient with severe AS in whom postoperative AR subsequently developed. The figure demonstrates that as little as 15 ml of additional LV diastolic volume led to LV filling pressures high enough to cause pulmonary edema at rest. Thus, even moderate acute post-TAVR AR would be expected to have significantly negative hemodynamic consequences, likely affecting survival. Further, the additional volume overload in the current study modestly impaired improvement in mitral regurgitation (MR), presumably because the volume overload from AR prevented reverse eccentric remodeling and reduction of functional MR. Persistent MR may also have affected survival.
Although it seems clear that significant AR after TAVR negatively affects prognosis, areas of uncertainty still exist. First. assessment of AR in most centers is qualitative or semiquantitative, at best. Thus, exactly how much additional diastolic volume is added is usually unknown. Further, each patient is different and as such has different LV compliance. It is likely that 15 ml of regurgitant volume may cause hemodynamic embarrassment in 1 patient’s stiff left ventricle but not in another patient with a more compliant ventricle. Thus, measurement of not only the amount of AR but also its effect on hemodynamics would be a better indicator of need to mechanically address post-TAVR AR. Second, post-deployment dilation has risks of its own, including annular rupture and possibly increased incidence of periprocedural stroke. When the benefit of the correction of AR outweighs these risks is as yet unknown. These issues may become moot in the relatively near future as newer valves are engineered to avoid post-deployment AR.
Post-TAVR aortic regurgitation reduces prognosis, almost certainly because of the adverse hemodynamics it imposes. Engineering the design of next-generation prostheses to prevent AR will be crucial to enhancing TAVR outcomes in the future. Meanwhile, improved understanding of when to address post-TAVR AR with additional manipulation will help Heart Team operators optimize outcomes for our shared patients.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Lerakis S.,
- Hayek S.S.,
- Douglas P.S.
- Genereux P.,
- Head S.J.,
- Hahn R.,
- et al.
- Althappan G.,
- Patvardhan E.,
- Tuzcu E.M.,
- et al.
- Hahn R.T.,
- Pibarot P.,
- Stewart W.J.,
- et al.
- Jerez-Valero M.,
- Urena M.,
- Webb J.G.,
- et al.
- Carabello B.A.
- Carabello B.A.,
- Gazes P.C.