Author + information
- Blase A. Carabello, MD∗ ()
- East Carolina Heart Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina
- ↵∗Address for correspondence:
Dr. Blase A. Carabello, East Carolina Heart Institute, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, North Carolina 27834.
Some things have to be true. Aortic stenosis (AS) obstructs outflow from the left ventricle, exerting a pressure overload on it, eventually causing left ventricular dysfunction and death; relief of that load relieves symptoms and saves lives. But how do we measure the obstruction? How much obstruction is needed to be pathological, and how big must the pressure overload be to cause damage? How much load must be removed to produce benefit? The report by Webb et al. (1) in this issue of the Journal sheds light on these topics while at the same time giving us important results of transcatheter aortic valve-in-valve replacement (VIV TAVR).
Structural valve deterioration has been known for decades to be the Achilles’ heel of bioprosthetic valves; this deterioration occurs progressively more frequently and sooner after implantation in younger versus older patients. However, most patients prefer bioprostheses to mechanical valves, wishing to avoid the risk of vitamin K antagonists required to reduce thromboembolic complications but which also increase the risk of hemorrhage. Thus, younger patients (age <60 years) often receive bioprosthetic aortic valve replacements that may require re-replacement 10 to 20 years later when patients are now in their seventh, eighth, or ninth decades of life. Indeed, in the current study (1), the majority of VIV TAVRs were placed in octogenarians who were >10 years’ post–initial implantation. Before VIV options, severe symptomatic structural valve deterioration would have required repeat heart surgery in invariably elderly patients, often compromised by the co-morbidities that accompany old age, putting such patients at high surgical risk. In fact, the Society of Thoracic Surgeons–predicted 30-day surgical mortality for the subjects in the current study was approximately 9%, whereas actual overall 30-day mortality for VIV TAVR was 2.7%. The complication rate was also acceptable and lower than what would have been predicted for surgery. The results of the report by Webb et al. are gratifying and offer our patients a safer recourse for failed bioprostheses than was available just a few years ago.
How Do These Data Inform Us?
Apart from the obvious clinical importance of the current study (1), the data contained in it offer some important insights into the nature of AS and parenthetically address some of the questions posed earlier. Parsing the study’s data is complicated by the admixture of patients with AS, those with mixed disease, and patients with predominantly aortic regurgitation. Seventy-six percent of the current patients had either AS or mixed disease (that behaves hemodynamically like AS) (2). There are several factors that we know or can reasonably assume from the data presented. Overall, the mean gradient decreased by 17 mm Hg, stroke volume decreased by 6 cc/m2, and ejection fraction (EF) increased by 4 EF percentage points. It is likely that stroke volume decreased because of correction of aortic regurgitation in those patients who had it and that EF increased because of a reduction in afterload in all patients that exceeded the reduction in preload in the patients with aortic regurgitation. Assuming that the pre-TAVR gradient for the patients with severe aortic regurgitation was 10 mm Hg from the data presented, the average gradient of the AS and mixed disease patients was approximately 43 mm Hg. Reducing that by 25 mm Hg (to 18 mm Hg) resulted in significant clinical improvement. This outcome is similar to the modest reduction in gradient reported by Quere et al. (3) (pre-operative mean gradient 30 mm Hg), relief of which also led to significant clinical and left ventricular improvement and also similar to that seen immediately after balloon aortic valvotomy. Taken together, the data suggest that a very modest reduction in afterload can lead to important clinical improvement, despite that the aortic valve area index was still in the “severe” range at 0.6 cm2/m2.
Perhaps the data are best explained by the study shown in Figure 1 (4). This study implies that individual variability to cope with pressure is prevalent wherein even a small gradient is tolerated poorly by some individuals (seen in the right-hand panel) and a small increase in gradient is even more poorly tolerated (recognizing that decreased stroke volume may have played a role). Conversely, it is then logical to postulate that even a small decrease in gradient might benefit some patients who have such an intolerance to pressure overload. Conversely, very low pre-operative gradients (<20 mm Hg) portend a poor outcome (5). It is likely that there is point at which the left ventricle is so sick that recovery is unusual or the reduction in load is so small that correction is ineffective. Accordingly, if the initial gradient is only 20 mm Hg or if the mean post-TAVR gradient is >20 mm Hg, mortality is increased, presumably because there was very little reduction in load (in the first case too little gradient to start with and in the second case too much to end with). Interestingly, although valve size ≤21 mm and severe patient–prosthesis mismatch (PPM) did not increase 1-year mortality, high gradient did.
Aortic valve area is an important measure of AS severity because it takes into account the stroke volume causing the gradient; however, cardiac output and reserve are likely to be muted in this elderly population, thus reducing the role of patient size in generating cardiac output. Furthermore, it must be recognized that PPM is a manmade definition. Although larger patients surely require larger valves to accommodate their flow requirements, normalizing valve area for body surface area has many pitfalls (6), a weakness in the definition of PPM.
Valve-in-Valve Should Raise the Flag of Caution
In the current series (1), VIV TAVR was used in a safe appropriate fashion to rescue patients at high surgical risk. This approach is a far cry from a prospective strategy in which a relatively young patient is advised to undergo AVR with a surgically implanted bioprosthesis with the hope of performing VIV TAVR if the first valve fails. Although PPM did not affect outcome in this series, post-procedure gradient did. To use a VIV strategy prospectively, a low gradient has to be assured and that seems less likely if a small valve is implanted. Thus, to use VIV as a planned prospective strategy, 2 prerequisites should be in place. First, there should be imaging techniques capable of accurately predicting the size of the surgically implanted valve. We take great pains to take this step before TAVR, and the same should be true for surgical AVR. Second, surgical skills must be available to safely enlarge the aortic root if needed, to accommodate at least a 23-mm bioprosthesis to avoid a high post–VIV TAVR gradient and its risk of mortality.
Webb et al. (1) have substantiated the feasibility, effectiveness, and safety of VIV TAVR for failed aortic bioprostheses in high-risk patients, most of whom had AS pathophysiology. It has to be true that it is the obstruction-caused pressure overload of AS that is the disease’s major pathological instrument. The data herein provide insight into how much pressure overload reduction is necessary to provide adequate clinical improvement. A reduction in mean gradient of as little as 25 mm Hg may be adequate in elderly, relatively sedentary patients, consistent with previous reports of temporary improvement after balloon aortic valvotomy (7). Conversely, a residual gradient of 20 mm Hg may constitute a significant residual pressure overload, impairing prognosis and promoting morbidity. High post-procedure gradient would be especially worrisome if it occurred in relatively young and active patients. In such patients, we need more data to tell us how to use VIV TAVR as a prospective strategy.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Carabello has reported that he has no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
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