Author + information
- Peter M. Eckman, MD∗ ()
- Department of Medicine, Division of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota
- ↵∗Reprint requests and correspondence:
Dr. Peter M. Eckman, Department of Medicine, Division of Cardiology, University of Minnesota, 420 Delaware Street SE, MMC 508, Minneapolis, Minnesota 55455.
Atrial fibrillation (AF) management poses challenges that are typically distilled into a simple question: rate control or rhythm control? Do the benefits of full anticoagulation outweigh the potential risks in this patient? As an internal medicine resident, I found AF management much less anxiety provoking than acute coronary syndromes. Hours of pathophysiology and lurking in the back of the room on rounds reinforced the relatively “benign” nature of AF. The AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study was published (1), I used the CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or TIA or thromboembolism) score (2), and learned how to address the simple questions. AF was quickly filed under “phone calls that I can handle alone.”
My confidence in managing AF was short-lived. There is nothing like practicing medicine to remind you on a daily basis how much you have yet to learn. AF is a common comorbidity in patients with heart failure (HF), and examples of AF triggering an acute HF decompensation were never hard to find, suggesting that maybe AF patients with concurrent HF should be treated differently. The AF-CHF (Atrial Fibrillation–Congestive Heart Failure) trial tested the hypothesis that AF prevention would improve survival in patients with HF with reduced ejection fraction but failed to find an advantage to a rhythm control strategy (3). However, it is hard to ignore the appeal of rhythm control, and we now place our hopes in a catheter-based rhythm control strategy (4). Results from prospective randomized trials such as RAFT-AF (A Randomized Ablation-based Atrial Fibrillation Rhythm Control Versus Rate Control Trial in Patients with Heart Failure and High Burden Atrial Fibrillation, NCT01420393) and CASTLE-AF (Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation, NCT00643188) are eagerly anticipated but could be our next helpings of humble pie. At least I did not have to worry too much about AF in my ventricular assist device (VAD) patients. All received anticoagulation therapy, and the relative importance of atrial function appeared inconsequential compared to the liters of flow that mechanical circulatory support can provide, nourishing previously flow-starved tissues and organs. Ventricular arrhythmias command a greater share of our attention, and if patients with VADs can tolerate ventricular fibrillation (5), one might assume that if it is hard to show an advantage to rhythm control in HF patients, it would be even harder to observe a difference in the VAD population. Finally, compared to the challenges of balancing risks of hemorrhage and thrombus in VADs, AF in this population was much lower on the priority list. Despite the frequency of AF in HF patients undergoing a VAD implant procedure, little has been published in this area, highlighting a gap in our understanding.
In this issue of the Journal, Enriquez et al. (6) have helped close this gap by reporting their study of the effect of AF in 106 patients who received a HeartMate II (Thoratec, Pleasanton, California) VAD. Most of the population (88%) received VAD implantations with the intention of acquiring a bridge to transplantation, and approximately 50% of patients had AF prior to implantation, a factor previously associated with increased risk of thromboembolic (TE) events after VAD (7). It is difficult to find clear data for the prevalence of AF in patients undergoing VAD implantation and appears to be on the high end. Of the 55 AF patients in this study, it was present prior to VAD implantation in all but 5, a number small enough to preclude definitive conclusions about the risk of adverse events following newly developed AF after HeartMate II implantation. Only 3 patients underwent surgical treatment (Cryo-Maze [Medtronic, Minneapolis, Minnesota] or left atrial appendage [LAA] ligation) that was presumed to have an impact on event risk. Although the anticoagulation regimen for patients without AF was lower (international normalized ratio [INR] goal of 1.5 to 2) than that used currently by most programs with HeartMate II, it was a common regimen during the study period, reflecting previously published data (8). Overall, although this report is from a single center, the subject population is reasonably comparable to that previously described receiving the VAD as a bridge to transplantation, with the potentially notable exception that the patients with AF in the present study were older (paroxysmal: 59.4 ± 9.8 years of age; persistent: 61.0 ± 8.3 years of age) than those in the HeartMate II bridge-to-transplantation trial (50.1 ± 13.1 years of age) (9).
The lack of associations among paroxysmal AF and mortality, HF hospitalization, bleeding, and TE events is reassuring, although a minor effect cannot be definitively excluded in this relatively small population. This finding suggests that any hemodynamic effect of intermittent AF in the HeartMate II population is likely to be minimal and that conventional anticoagulation is appropriate for this group.
The most notable finding, however, was that persistent AF was an independent predictor of death or HF hospitalization in patients who received a VAD in this study. The effect was stronger for HF hospitalization (hazard ratio [HR]: 7.37; p < 0.01) and barely missed achieving statistical significance for mortality (HR: 2.65; p = 0.06). In Figure 1 in the Enriquez et al. article (6), it appears to be approximately 75 days after implantation that the groups diverge, a time point at which the greatest risks of implantation such as acute right ventricular failure have passed. Can we, perhaps, speculate about the mechanism by which persistent AF appears to affect outcomes based on this time of divergence? Inability to fully engage in rehabilitation due to poor exercise tolerance, borderline right ventricular function, and ventricular arrhythmias are often prominent issues at 1 to 2 months after implantation. We could hypothesize that persistent AF would lead to more aggressive use of beta blockers, which could impair right ventricular function and chronotropic response. It is unfortunate (although typical) that only 35 patients in this cohort had cardiopulmonary testing after VAD implantation, a group size that is underpowered to draw conclusions about the impact of AF on exercise capacity, much less begin to attribute impairment to any specific factor, such as use of a specific class of medications. Comparison between individual exercise test results of paroxysmal AF patients and those of sinus rhythm patients might help to further our understanding of the mechanism by which persistent AF impacts outcomes. Unfortunately, reviewing the causes of death (Table 3 in the Enriquez et al. article ) does not provide a very satisfying clue to the mechanism for possibly increased risk of mortality, as the suggestion of increased risk of death from sepsis in the persistent AF group is hard to attribute to AF burden.
Another important finding was that TE events in patients with AF occurred despite a higher INR at the time of event, as shown in Figure 4 in the Enriquez et al. article (6). Alternatively, this study’s finding could be taken as evidence that the risk of TE complications is very low in the absence of AF and the presence of INR >2. Because the single TE event observed in the persistent AF group could be a consequence of the sample size, it raises the question of whether the mechanism of TE events (especially neurologic) in the VAD population is the same as in patients with natural circulation. For example, if we presume that emboli originated in the LAA and that most blood flows through the VAD, we would expect the debris that would navigate the device and arrive in the cerebral vasculature to be quite small. The smallest gap in the HeartMate II, for example, is approximately 0.003 inches, according to the manufacturer. Altered flow in the ascending aorta from the outflow graft might also be expected to alter the cerebral distribution of infarctions, even if thromboemboli escape the heart through the aortic valve. We also might expect thrombi to form in the proximal aorta from stasis resulting from infrequent opening of the aortic valve, which would be expected to be independent of AF.
Should patients who receive a VAD and have AF have a more aggressive INR goal, such as 2.0 to 3.0 rather than 2.0 to 2.5? Optimizing anticoagulation in the VAD population to minimize morbidity and mortality remains one of the “holy grails” of mechanical circulatory support and must be balanced against the increased risk of bleeding. The risk of fatal intracranial hemorrhage in this study was approximately 4% (2 of 55 patients) in the AF group and zero in the group of patients without AF, highlighting the potential cost to more aggressive anticoagulation. Validation of these findings in larger cohorts and additional centers would be important before advocating significant changes in the anticoagulation protocols currently recommended. Another important consideration that this study raises is whether we should pursue a rhythm control strategy in VAD patients with AF. The limitations of pharmacologic therapy to maintain sinus rhythm are well known. The risk-benefit profile of pulmonary vein isolation in patients with VAD is completely unknown, but these findings tantalize us once again with the hope that rhythm control will be the superior strategy. A trial of the role of surgical treatment (LAA ligation, concurrent Cox maze procedure) at the time of VAD implantation would have ample justification. It also might advance our understanding of the mechanism of cerebrovascular infarction in the VAD population, if such a trial were negative, implying that the pathophysiology of infarction from AF in this group may indeed be different.
Enriquez et al. (6) have identified an important signal that persistent AF in the CF-VAD population portends increased risk of HF hospitalization and, potentially, mortality. This should stimulate additional work to help the field understand the mechanisms, which may help us understand the consequences of AF in the much larger population who do not have a VAD.
↵∗ 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. Eckman has received clinical trial support and consulting and educational fees from Thoratec; and clinical trial support and honoraria from HeartWare (all have been modest and are reviewed annually by the University of Minnesota).
- American College of Cardiology Foundation
- Gage B.F.,
- van Walraven C.,
- Pearce L.,
- et al.
- Trulock K.M.,
- Narayan S.M.,
- Piccini J.P.
- Enriquez A.D.,
- Calenda B.,
- Gandhi P.U.,
- Nair A.P.,
- Anyanwu A.C.,
- Pinney S.P.