Waiting for guideline-based ‘triggers’ before addressing severe AR may harm survival

Patients with severe aortic regurgitation (AR) may be better off receiving valve operations before symptoms appear that “trigger” guideline recommendations for these surgeries, according to a new study in JACC: Cardiovascular Imaging.

The research relates to the clinical conundrum of “watchful waiting” versus earlier intervention in patients with severe AR.

Both European and American guidelines define triggers for AR surgery, broken into classes. Class I triggers, including heart failure symptoms and impaired left ventricular ejection fraction (LVEF), are enough to prompt surgery. Class II triggers, mostly related to volume overload, leave some room for clinical judgment.

But these triggers were based on studies performed in the 1990s—with patients operated on even earlier—so any improvements in long-term survival and operational techniques for AR may shift the value of intervening at different time points, Christophe de Meester, PhD, and colleagues wrote in the study.

The researchers studied 356 patients undergoing surgery for severe AR at the Cliniques Universitaires Saint-Luc in Brussels from 1995 through 2014. Adjusted 10-year survival was significantly better for patients who underwent surgery without operative triggers (89 percent) or with Class II triggers (85 percent) compared to those with Class I triggers (71 percent). Rates of cardiovascular mortality and heart failure hospitalizations were also lower in those with no triggers or Class II triggers versus Class I triggers.

The authors also found mortality increases began once LVEF dipped below 55 percent and once LV end-systolic dimension (LVESD) increased above 20 to 22 mm/m2—suggesting patients should be operated on before symptoms develop and before those thresholds are reached. This, too, might require guidelines to be re-evaluated; they use LVEF of 50 percent or lower and LVESD of 25 mm/m2 or higher as the triggers.

“Patients with mild preoperative symptoms (Class II) have usually been grouped with truly asymptomatic patients and were therefore not promptly referred to surgery,” de Meester et al. wrote. “The present study indicates that these patients incur a poorer postoperative survival than patients who were strictly asymptomatic preoperatively. Because this outcome penalty persisted after adjustment for baseline characteristics, we believe these patients should be referred to surgery before the onset of symptoms.”

Notably, LV end-diastolic dimensions, which have been included as Class IIb triggers for AR surgery, weren’t significantly associated with outcomes.

The researchers pointed out most of their patients received aortic valve repair rather than replacement, so it is unknown whether similar results would apply to replacement procedures. They also acknowledged only a randomized trial could definitively prove earlier intervention would result in better outcomes for patients like those in their study, but maintained their results raise important questions regarding the current AR surgery guidelines.

“Guideline-based triggers for AR surgery carry major independent risk implications for long-term outcomes,” de Meester and co-authors wrote. “Class I triggers should be avoided because they imply higher postoperative long-term mortality and higher (heart failure) rates. Among Class II triggers, those linked to LV dilatation at end-systole carry the same risk as LVEF and should probably be considered as Class I triggers.”