Maybe Atrial Fibrillation DOES Matter in Ventricular Assist Device Patients?∗

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 64, NO. 18, 2014

ª 2014 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.

ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2014.08.031

EDITORIAL COMMENT

Maybe Atrial Fibrillation DOES Matter in Ventricular Assist Device Patients?* Peter M. Eckman, MD

A

trial fibrillation (AF) management poses

control strategy (3). However, it is hard to ignore the

challenges that are typically distilled into a

appeal of rhythm control, and we now place our

simple question: rate control or rhythm con-

hopes in a catheter-based rhythm control strategy

trol? Do the benefits of full anticoagulation outweigh

(4). Results from prospective randomized trials such

the potential risks in this patient? As an internal med-

as RAFT-AF (A Randomized Ablation-based Atrial

icine resident, I found AF management much less

Fibrillation Rhythm Control Versus Rate Control Trial

anxiety provoking than acute coronary syndromes.

in Patients with Heart Failure and High Burden Atrial

Hours of pathophysiology and lurking in the back

Fibrillation, NCT01420393) and CASTLE-AF (Catheter

of the room on rounds reinforced the relatively

Ablation Versus Standard Conventional Treatment

“benign” nature of AF. The AFFIRM (Atrial Fibrilla-

in Patients With Left Ventricular Dysfunction and

tion Follow-up Investigation of Rhythm Manage-

Atrial Fibrillation, NCT00643188) are eagerly antici-

ment) study was published (1), I used the CHADS2

pated but could be our next helpings of humble pie.

(congestive heart failure, hypertension, age, diabetes

At least I did not have to worry too much about

mellitus, prior stroke or TIA or thromboembolism)

AF in my ventricular assist device (VAD) patients. All

score (2), and learned how to address the simple

received anticoagulation therapy, and the relative

questions. AF was quickly filed under “phone calls

importance of atrial function appeared inconsequen-

that I can handle alone.”

tial compared to the liters of flow that mechanical

My confidence in managing AF was short-lived.

circulatory support can provide, nourishing previ-

There is nothing like practicing medicine to remind

ously flow-starved tissues and organs. Ventricular

you on a daily basis how much you have yet to learn.

arrhythmias command a greater share of our atten-

AF is a common comorbidity in patients with heart

tion, and if patients with VADs can tolerate ven-

failure (HF), and examples of AF triggering an acute

tricular fibrillation (5), one might assume that if it

HF decompensation were never hard to find, sug-

is hard to show an advantage to rhythm control in

gesting that maybe AF patients with concurrent HF

HF patients, it would be even harder to observe a

should be treated differently. The AF-CHF (Atrial

difference in the VAD population. Finally, compared

Fibrillation–Congestive Heart Failure) trial tested the

to the challenges of balancing risks of hemorrhage

hypothesis that AF prevention would improve sur-

and thrombus in VADs, AF in this population was

vival in patients with HF with reduced ejection frac-

much lower on the priority list. Despite the fre-

tion but failed to find an advantage to a rhythm

quency of AF in HF patients undergoing a VAD implant procedure, little has been published in this area, highlighting a gap in our understanding.

*Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the

SEE PAGE 1883

views of JACC or the American College of Cardiology. From the Department of Medicine, Division of Cardiovascular Medicine,

In this issue of the Journal, Enriquez et al. (6) have

University of Minnesota, Minneapolis, Minnesota. Dr. Eckman has

helped close this gap by reporting their study of the

received clinical trial support and consulting and educational fees from Thoratec; and clinical trial support and honoraria from HeartWare (all

effect of AF in 106 patients who received a HeartMate II

have been modest and are reviewed annually by the University of

(Thoratec, Pleasanton, California) VAD. Most of the

Minnesota).

population (88%) received VAD implantations with

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Eckman

JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1891–3

AF in VAD Patients

the intention of acquiring a bridge to transplantation,

at 1 to 2 months after implantation. We could hy-

and approximately 50% of patients had AF prior to

pothesize that persistent AF would lead to more

implantation, a factor previously associated with

aggressive use of beta blockers, which could impair

increased risk of thromboembolic (TE) events after

right ventricular function and chronotropic response.

VAD (7). It is difficult to find clear data for the preva-

It is unfortunate (although typical) that only 35 pa-

lence of AF in patients undergoing VAD implantation

tients in this cohort had cardiopulmonary testing

and appears to be on the high end. Of the 55 AF patients

after VAD implantation, a group size that is under-

in this study, it was present prior to VAD implantation

powered to draw conclusions about the impact of AF

in all but 5, a number small enough to preclude defin-

on exercise capacity, much less begin to attribute

itive conclusions about the risk of adverse events

impairment to any specific factor, such as use of a

following newly developed AF after HeartMate II

specific class of medications. Comparison between

implantation. Only 3 patients underwent surgical

individual exercise test results of paroxysmal AF pa-

treatment (Cryo-Maze [Medtronic, Minneapolis, Min-

tients and those of sinus rhythm patients might

nesota] or left atrial appendage [LAA] ligation) that

help to further our understanding of the mechanism

was presumed to have an impact on event risk.

by which persistent AF impacts outcomes. Unfortu-

Although the anticoagulation regimen for patients

nately, reviewing the causes of death (Table 3 in

without AF was lower (international normalized ratio

the Enriquez et al. article [6]) does not provide a

[INR] goal of 1.5 to 2) than that used currently by most

very satisfying clue to the mechanism for possibly

programs with HeartMate II, it was a common regimen

increased risk of mortality, as the suggestion of

during the study period, reflecting previously pub-

increased risk of death from sepsis in the persistent

lished data (8). Overall, although this report is from a

AF group is hard to attribute to AF burden.

single center, the subject population is reasonably

Another important finding was that TE events in

comparable to that previously described receiving the

patients with AF occurred despite a higher INR at the

VAD as a bridge to transplantation, with the potentially

time of event, as shown in Figure 4 in the Enriquez

notable exception that the patients with AF in the

et al. article (6). Alternatively, this study’s finding

present study were older (paroxysmal: 59.4
9.8 years

could be taken as evidence that the risk of TE com-

of age; persistent: 61.0
8.3 years of age) than those

plications is very low in the absence of AF and

in the HeartMate II bridge-to-transplantation trial

the presence of INR >2. Because the single TE event

(50.1
13.1 years of age) (9).

observed in the persistent AF group could be a

The lack of associations among paroxysmal AF

consequence of the sample size, it raises the question

and mortality, HF hospitalization, bleeding, and TE

of whether the mechanism of TE events (especially

events is reassuring, although a minor effect cannot

neurologic) in the VAD population is the same as in

be definitively excluded in this relatively small pop-

patients with natural circulation. For example, if

ulation. This finding suggests that any hemodynamic

we presume that emboli originated in the LAA and

effect of intermittent AF in the HeartMate II popula-

that most blood flows through the VAD, we would

tion is likely to be minimal and that conventional

expect the debris that would navigate the device and

anticoagulation is appropriate for this group.

arrive in the cerebral vasculature to be quite small.

The most notable finding, however, was that

The smallest gap in the HeartMate II, for example, is

persistent AF was an independent predictor of death

approximately 0.003 inches, according to the manu-

or HF hospitalization in patients who received a VAD

facturer. Altered flow in the ascending aorta from

in this study. The effect was stronger for HF hospi-

the outflow graft might also be expected to alter the

talization (hazard ratio [HR]: 7.37; p < 0.01) and

cerebral distribution of infarctions, even if throm-

barely missed achieving statistical significance for

boemboli escape the heart through the aortic valve.

mortality (HR: 2.65; p ¼ 0.06). In Figure 1 in the

We also might expect thrombi to form in the proximal

Enriquez et al. article (6), it appears to be approxi-

aorta from stasis resulting from infrequent opening

mately 75 days after implantation that the groups

of the aortic valve, which would be expected to be

diverge, a time point at which the greatest risks of

independent of AF.

implantation such as acute right ventricular failure

Should patients who receive a VAD and have AF

have passed. Can we, perhaps, speculate about the

have a more aggressive INR goal, such as 2.0 to 3.0

mechanism by which persistent AF appears to affect

rather than 2.0 to 2.5? Optimizing anticoagulation in

outcomes based on this time of divergence? Inability

the VAD population to minimize morbidity and mor-

to fully engage in rehabilitation due to poor exercise

tality remains one of the “holy grails” of mechanical

tolerance, borderline right ventricular function, and

circulatory support and must be balanced against the

ventricular arrhythmias are often prominent issues

increased

risk

of

bleeding.

The

risk

of

fatal

Eckman

JACC VOL. 64, NO. 18, 2014 NOVEMBER 4, 2014:1891–3

AF in VAD Patients

intracranial hemorrhage in this study was approxi-

might advance our understanding of the mechanism

mately 4% (2 of 55 patients) in the AF group and zero

of cerebrovascular infarction in the VAD population,

in the group of patients without AF, highlighting the

if such a trial were negative, implying that the path-

potential cost to more aggressive anticoagulation.

ophysiology of infarction from AF in this group may

Validation of these findings in larger cohorts and

indeed be different.

additional centers would be important before advo-

Enriquez et al. (6) have identified an important

cating significant changes in the anticoagulation

signal that persistent AF in the CF-VAD population

protocols currently recommended. Another impor-

portends increased risk of HF hospitalization and,

tant consideration that this study raises is whether

potentially, mortality. This should stimulate addi-

we should pursue a rhythm control strategy in VAD

tional work to help the field understand the me-

patients with AF. The limitations of pharmacologic

chanisms, which may help us understand the

therapy to maintain sinus rhythm are well known.

consequences of AF in the much larger population

The risk-benefit profile of pulmonary vein isolation in

who do not have a VAD.

patients with VAD is completely unknown, but these findings tantalize us once again with the hope that

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

rhythm control will be the superior strategy. A trial

Peter M. Eckman, Department of Medicine, Division

of the role of surgical treatment (LAA ligation, con-

of Cardiology, University of Minnesota, 420 Delaware

current Cox maze procedure) at the time of VAD im-

Street SE, MMC 508, Minneapolis, Minnesota 55455.

plantation would have ample justification. It also

E-mail: [email protected].

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fibrillation: contemporary challenges including the role of ablation. J Am Coll Cardiol 2014;64:710–21.

device implantation. Ann Thorac Surg 2013;96: 2161–7.

5. Naito N, Kinoshita O, Ono M. Prolonged left

8. Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anticoagulation. J Heart Lung Transplant 2009;28:881–7.

ventricular assist device support (18 months) in refractory ventricular fibrillation. J Heart Lung Transplant 2014;33:772–3. 6. Enriquez AD, Calenda B, Gandhi PU, Nair AP, Anyanwu AC, Pinney SP. Clinical impact of atrial fibrillation in patients with the HeartMate II left ventricular assist device. J Am Coll Cardiol 2014; 64:1883–90.

9. Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007;357:885–96.

7. Stulak JM, Deo S, Schirger J, et al. Preoperative atrial fibrillation increases risk of thromboembolic events after left ventricular assist

KEY WORDS atrial fibrillation, thromboembolic events, ventricular assist device

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