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\begin{document}

\title{A Time May Soon Be At Hand}



\author[1]{Saqib Masroor}%
\author[2]{Donlad Glower}%
\affil[1]{University of Toledo Medical Center}%
\affil[2]{Duke University Medical Center}%


\vspace{-1em}



  
  \date{May 18, 2024}


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\textbf{Title:} The Time May Soon Be At Hand

\textbf{Running Head:} Time May Soon Be At Hand

\textbf{Authors:} Saqib Masroor, MD\textsuperscript{1} and Donald B.
Glower MD\textsuperscript{2}

1. University of Toledo College of Medicine and Life Sciences,
Department of Surgery, Division of Cardiothoracic Surgery

2. Duke University Medical Center, Department of Surgery, Division of
Cardiothoracic Surgery

\textbf{Meeting Presentation:} None

\textbf{Disclosure:} None

\textbf{Word Count:} 1213

\textbf{Corresponding Author:}

Saqib Masroor, MD, MHS

Chief, Division of Cardiothoracic Surgery

University of Toledo College of Medicine and Life Sciences

3000 Arlington Avenue, Toledo, Ohio 43614

Phone: 419-383-5150

Fax: 419-383-3149

Surgeons have usually associated left atrial appendectomy (or exclusion)
as a part of the Maze procedure or some iteration thereof. However the
strategy of left atrial appendectomy to prevent embolism in patient with
rheumatic heart disease and atrial fibrillation was first implemented by
Madden in 1949, long before the Maze procedure was developed (1). Not
soon thereafter it was also shown that ligation of LAA can still lead to
embolism (2), thereby demonstrating that in order to prevent embolism in
patients with AF undergoing LAA excision/exclusion, the surgical
technique is also important. Years later, in his report of 306 patients
(3) who underwent maze procedure and followed for up to 11.5 years, Dr
Cox reported two early strokes with an incidence of 0.7\% and only one
more stroke in the follow-up period. This benefit was ascribed to the
maze procedure restoring sinus rhythm and atrial transport, and
secondarily to obliteration of the LAA. Since that time, many studies
have reported on the success of the maze procedure in restoring sinus
rhythm as well reducing the incidence of stroke in patients with AF
(4-5).

However, two questions remain. First, is the stroke reduction by maze
procedure due to restoration of rhythm or due to obliteration of the
LAA? Second, is the surgical technique important in successful
obliteration of LAA?

In this issue of the Journal of Cardiac Surgery, Jiang et al (6), report
on 860 patients undergoing mitral valve replacement, who were randomized
to LAA exclusion (n = 521) vs no exclusion (n = 339). The primary
endpoint was perioperative stroke within 30 days of surgery. This was a
relatively younger population with a mean age of 53 years including 68\%
with rheumatic disease. Not unexpectedly, almost 20\% of these patients
had a mural thrombus in the LAA. None of the patients underwent surgical
ablation for AF. Most patients underwent concomitant valve or coronary
artery bypass grafting. The exclusion group had significantly reduced
incidence of stroke at 0.6\% vs no-exclusion group which had a stroke
incidence of 2.7\% (p \textless{}0.05). However further subgroup
analysis revealed that this benefit was limited to the patients who had
pre-operative AF. In these patients with pre-existing AF (n = 543), 373
underwent exclusion and 170 did not. The incidence of stroke in the
exclusion group was 1/14\textsuperscript{th} that in the no-exclusion
group (0.3\% vs 4.5\%). In patients without pre-existing AF (n = 323),
no statistically significant benefit of LAA exclusion was seen in the
reducing the risk of perioperative stroke, even though 17.6\% of these
patients did develop postoperative AF.

This is the first randomized study to demonstrate the benefit of LAA
exclusion, without rhythm restoration, in reducing perioperative stroke
in patients with AF undergoing mitral valve replacement. The benefit
appears to be similar in magnitude to the historical control reported by
Dr Cox (3). None of the patients received any ablation as the maze
procedure. This study also demonstrates the importance of the surgical
technique in LAA exclusion. The authors focus on two principles of LAA
closure. The first is reducing the tension at the suture line of the LAA
orifice, by what can be described as a plicating stitch, which pulls the
left atrial tissue up towards the posterior mitral annulus, thereby
reducing the tension at the orifice of the LAA. Secondly, the two-layer
closure - a horizontal mattress suture followed by the running
over-sewing layer of monofilament suture -- makes for a durable closure
of LAA, as demonstrated by their excellent outcomes.

However, there are many shortcomings of this study. This is a relatively
short study with only perioperative outcomes at 30 days after surgery.
Longer term follow-up would have been better. Secondly, even though the
groups were randomized, there are many differences in the two groups,
including the gender distribution, incidence of hypertension, LV
dysfunction, pre-existing AF, presence of mural thrombus, concomitant
tricuspid valve surgery; all of which had a higher proportion of
patients in the exclusion group as compared to the no-exclusion group.
In order to balance the confounding variables between the two groups, it
would have been better if the authors had used a propensity score
matching strategy.

In addition to 3 randomized trials already in the literature (7-9) and
the study of Jiang et al. (6), there are 2 ongoing randomized trials
examining LAA exclusion. These include the Left Atrial Appendage
Occlusion Study (LAAOS) III trial in 4700 patients with AF undergoing
cardiac surgery (10) and the AtriClip Left Atrial Appendage Exclusion
Concomitant to Structural Heart Procedures (ATLAS) trial in 2000
patients without AF but at high risk to develop postoperative AF
(ClinicalTrials.gov Identifier: NCT02701062).

At present, surgical exclusion of the LAA has only a Class IIb
indication for patients with AF undergoing cardiothoracic surgery by ESC
(11) and ACC/AHA (12) guidelines. However, within the next 2 years we
may have 6 randomized trials likely to warrant changes in the national
and international practice guidelines. That time may soon be at hand!

References

\begin{enumerate}
\tightlist
\item
  Madden JL. Resection of the left auricular appendix. J Am Med Assoc
  1949;140(9):769-72
\item
  Leonard FC and Cogan MA. Failure of ligation of the left auricular
  appendage in the prevention of recurrent embolism. N Engl J Med
  1952;246(19):733-5
\item
  Cox JL, Ad N and Palazzo T. Impact of the maze procedure on the stroke
  rate in patients with atrial fibrillation. J Thorac Cardiovasc Surg
  1999;118:833-40
\item
  Kim JB, Yun TJ, Chung CH, et al. Long term outcome of modified maze
  procedure combine with mitral valve surgery: Analysis of outcomes
  according to type of mitral valve surgery. J Thorac Cardiovasc Surg
  2010;139:111-7
\item
  Bando K, Kasegawa H, Okada Y, et al. Impact of preoperative and
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\item
  Jiang S, Zhang H, Wei S, et al. Left atrial appendage exclusion is
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  Whitlock RP, Vincent J, Blackall MH, Hirsh J, Fremes S, Novick R, et
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\item
  Nagpal AD, Torracca L, Fumero A, Denti P, Cioni M, Alfieri O.
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  Healey JS, Crystal E, Lamy A, Teoh K, Semelhago L, Hohnloser SH, et
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  Whitlock R, Healey J, Vincent J, Brady K, Teoh K, Royse A, et al.
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  Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et
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\item
  January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC
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\end{enumerate}

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