A-fib, Whether Preexisting or New-Onset, Tied to Poor Outcomes in TAVR

Whether it manifests before or after TAVR, A-fib in patients with severe aortic stenosis is associated with higher mortality and morbidity at 1 year, according to a study published in the August 24, 2015, issue of JACC: Cardiovascular Interventions.

“The higher rate of death observed in preexisting [A-fib] patients seems to be linked to heart failure, whereas the poorer outcome in patients in whom new-onset [A-fib] developed after [TAVR] could be related to the procedure,” write Romain Chopard, MD, PhD, of University Hospital Besançon (Besançon, France), and colleagues.

Investigators looked at 3,875 patients from the FRANCE-2 registry who had TAVR performed at 34 centers in France and Monaco between January 2010 and December 2011. About one-quarter (25.8%) of patients had documented A-fib prior to the procedure. These patients were more frequently male, older, and more likely to present with comorbidities and worse NYHA functional class than those without A-fib. Additionally, new-onset A-fib was recorded in 174 patients (6.0%), who also were more likely to be older and present with a higher rate of previous stroke compared with those remaining  in sinus rhythm.

Preexisting A-fib Ups Risk

Between patients with and without preexisting A-fib, the rate of postprocedural aortic regurgitation grade 2 or higher did not differ. However, preexisting A-fib was associated with lower LVEF, higher pulmonary pressure, and a higher rate of significant mitral regurgitation.

Mortality and overall procedure-related complications—including the combined safety endpoint (all-cause mortality, stroke, life-threatening bleeding, acute kidney injury stage 2 or 3, coronary artery obstruction requiring intervention, major vascular complication, or valve-related dysfunction requiring repeat intervention)—were similar between the groups within the first 30 days post-TAVR.

But at 1 year, all-cause and cardiovascular death were higher among patients with preexisting A-fib (P < .001 for both), while stroke and major bleeding did not differ (table 1).

Preexisting A-fib was the second most powerful predictor—with the first being postprocedural aortic regurgitation of at least grade 2—of the combined efficacy endpoint (all-cause mortality, stroke, need for hospitalization for valve-related symptoms or worsening congestive heart failure, NYHA functional class III or IV, valve-related dysfunction, and/or moderate or severe prosthetic valve regurgitation) on Cox analysis (P < .001 for both).

On echocardiographic follow-up, those with preexisting A-fib still had lower LVEF and higher pulmonary pressure and significant mitral regurgitation than those without.

New-Onset A-fib Also Dangerous

Device success and postprocedural aortic regurgitation were similar between those with and without new-onset A-fib after TAVR. However, access other than transfemoral was more frequently used in patients who developed the condition, as was the rate of VARC 2-defined cardiac and hemorrhagic procedure-related events. Hospital stay was longer among patients with new-onset A-fib after TAVR compared with those with no A-fib (12.5 vs 9.9 days; P < .001).

All-cause death at 1 year was higher in those with new-onset A-fib vs without (20.7% vs 11.1%; P = .003), as was the occurrence of the combined efficacy endpoint (41.9% vs 29.1%; P = .02). No differences were seen for any other endpoint.

Independent predictors of new-onset A-fib were a history of stroke (HR 1.66; 95% CI 1.05-2.63), surgical nontransfemoral approach (HR 2.04; 95% CI 1.47-2.81) , and cardiac (HR 1.59; 95% CI 1.08-2.36) and hemorrhagic procedure-related events (HR 1.56; 95% CI 1.004-2.45).

Lastly, Cox analysis showed that, following chronic kidney disease, new-onset A-fib was the second most powerful predictor of the combined efficacy endpoint (P < .001 for both).

Adjusting Risk Scores

“Our results are in line with and strengthen preliminary reports from 2 previous registries and from 2 specific reports. However, these previous studies included limited sample sizes (fewer than 400 patients in each study), and found a 1.44- to 4.11-fold increased risk of all-cause mortality at 1 year,” write Dr. Chopard and colleagues. “In light of these results, the inclusion of preexisting [A-fib] in future risk scores specifically dedicated to selection of patients for either TAVI or [surgery] should be considered.”

Compared with what has been seen with surgical repair, the prevalence of new-onset A-fib in TAVR patients was lower, they say, “but pathophysiological mechanisms could share some common features, especially in the case of a transapical approach.” Thoracic surgery experience has taught that thoracotomy is associated with new-onset A-fib “due to the ventilatory restriction and the hyperadrenergic status generated by postoperative pain,” while bleeding events and myocardial injury such as LV repair or cardiac complications “were previously shown to be strongly related to the occurrence of new-onset [A-fib] after open-heart surgery,” the authors explain.

Preexisting A-fib should be included in future risk scores for both TAVR and surgery, they suggest. “[S]pecific postprocedural management could be envisaged for patients in whom new-onset [A-fib] develops after TAVI.”

How Problematic is A-fib Alone?

In an accompanying editorial, Jonathon M. White, MD, and Susheel K. Kodali, MD, both of the NewYork-Presbyterian Hospital/Columbia University Medical Center (New York, NY), say the study is important because “it is the first, large registry-based analysis to describe the scope of the [A-fib] problem and its potential role in modifying risk in inoperable TAVR patients.” 

But “whether [A-fib] truly modifies risk in these patients or merely reflects other comorbidity and worse heart failure is impossible to know,” they write. “Indeed, the investigators surmise that worse heart failure might drive the worse outcomes observed in [A-fib] patients.”

Further study is needed to know if A-fib “is problematic in and of itself,” the editorialists observe. “Data supporting improved outcomes from the restoration or maintenance of sinus rhythm in the general population are lacking and whether such strategies might benefit TAVR patients is not known.”

In an email with TCTMD, Josep Rodés-Cabau, MD, of the Quebec Heart and Lung Institute (Quebec City, Canada), said that future studies could focus on both how to reduce the occurrence of new-onset A-fib and how to mitigate the risks it carries.

Improvement in clinical outcomes is dependent on a better understanding of the complex relationship between A-fib, heart failure, and procedural outcomes, including stroke and bleeding, the editorialists add. “What is clear, however, is that inoperable patients with [A-fib] carry a large burden of cardiovascular disease and should be considered for comprehensive heart failure and antithrombotic treatment, all directed at reducing the long-term consequences of heart failure even after relief of valvular obstruction from aortic stenosis.”

Sources: 
1. Chopard R, Teiger E, Meneveau N, et al. Baseline characteristics and prognostic implications of pre-existing and new-onset atrial fibrillation after transcatheter aortic valve implantation: results from the FRANCE-2 registry. J Am Coll Cardiol Intv. 2015;8:1346-1355.
2. White JM, Kodali SK. Atrial fibrillation and transcatheter aortic valve replacement: the burden of advanced cardiovascular disease in aortic stenosis [editorial]. J Am Coll Cardiol Intv. 2015;8:1356-1358.

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• Preexisting—But Not New-Onset—A-fib Predicts Worse Long-term Outcomes After TAVR
• A-fib, Dialysis Dramatically Worsen Outlook for TAVR Patients with Advanced CKD
• A-fib Common After Aortic Valve Replacement