Study Shows Aortic Valve Replacement Was Associated With Better Outcomes in Patients with Low-Gradient Aortic Stenosis and Preserved Left Ventricular Ejection Fraction Compared With High-Gradient Aortic Stenosis Analysis of PARTNER 2A randomized trial and SAPIEN 3 registry

Sahar Memar Montazerin, MD
By Sahar Memar Montazerin, MD on

A recent study by Dr. Salaun, published in Circulation: Cardiovascular Interventions, demonstrated that aortic valve replacement in patients with the low gradient (LG, defined as mean gradient <40 mmHg) severe aortic stenosis (AS) and preserved ejection fraction (EF) has resulted in better outcomes versus in those with the high gradient (HG, defined as a mean transvalvular gradient (MG) 40 mmHg) AS. Also, the study revealed that patients with classical low flow, low gradient (CLF-LG, defined as MG <40 mmHg and LVEF <50%) AS were at higher risk of death, rehospitalization, or stroke at 2 years.

Aortic stenosis is one of the most common valvular heart diseases, especially among elderly individuals. Aortic valve replacement (AVR) is recommended for patients with severe AS and left ventricular EF < 50% by the current American Heart Association guideline. Previous studies have supported the beneficial effects of AVR in the survival of patients with high gradient severe AS. However, there is conflicting data in this regard for patients with low gradient severe AS. The analysis of the PARTNER 2A randomized trial and SAPIEN 3 registry addressed this issue.

This analysis included 3511 patients from the PARTNER 2 Cohort A randomized trial (n=1910) and SAPIEN 3 registry (n=1601). Transthoracic echocardiography was performed in all the participants at the baseline to identify the pattern of the flow-gradient and at follow-ups. All the participants had symptomatic severe AS which is defined as having aortic valve area lowe than 1.0 cm2. AS subclassified to the following four categories based on the flow gradient pattern: 1) HG, defined as a mean transvalvular gradient (MG) 40 mmHg; 2) CLF-LG, defined as MG <40 mmHg and LVEF <50%; 3) paradoxical low flow, low gradient (PLF-LG),  defined as MG <40 mmHg, LVEF 50%, and stroke volume index <35 mL/m2; 4) normal-flow, low gradient (NF-LG), defined as MG <40 mmHg, LVEF 50%, and stroke volume index 35 mL/m2.  The primary endpoints were death, rehospitalization for heart failure symptoms or valve prosthesis complications as well as stroke within the first 2 years following AVR.

The analysis has demonstrated that 2229 individuals (63.5%) had HG AS. Of the 1282 (36.5%) with LG pattern, 689 patients (19.6%) had a CLF-LG AS, 247 (7.0%)had a PLF-LG AS, and 346 (9.9%) had an NF-LG AS. Over the 2-years follow-up period, the primary endpoints of the study were observed in 31. 8% HG, 38.8% of CLF LG, 33.6 % of PLF LG, and 32.1% of NF LG. CLF was the most prevalent subtype of the LG AS and was significantly associated with worse outcomes versus the HG pattern (P=0.002). No statistically significant differences were observed between HG and other subtypes of LG flow patterns. Even after adjustment for baseline risk factors, comorbidities, surgical risk score, and type of AVR, the association between CLF LG and worse primary outcomes remained consistent. Also, the 2-year rates of clinical events were reported to be similar between the transcatheter AVR versus surgical AVR in the whole group and among flow gradient patterns. 

There are some limitations to consider while interpreting the results of this study: The PARTNER inclusion criteria affect the sample population, and the various flow gradient estimates in this study may not be representative of the real-life practice. The Doppler echocardiography which has been used for the evaluation of AS severity is another limitation. As the flow gradient or left ventricular outflow tract diameter might have been underestimated.

Finally, this study supported the consideration of AVR in patients with severe LG AS and preserved EF. However, for patients with severe LG AS and reduced EF, AVR may lead to worse outcomes compared to HG AS. Future randomized clinical trials are needed to further compare its safety and efficacy versus conservative management in this population.





Leave a Reply