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\begin{document}

\title{Open Thoracoabdominal Aortic Aneurysm Repair in Cardiopulmonary Testing
Era: A Correlative Cohort Analysis}



\author[1]{Damian  Bailey}%
\author[2]{Claire Halligan}%
\author[3]{Richard Davies}%
\author[4]{Anthony Funnell}%
\author[3]{Ian Appadurai}%
\author[1]{George Rose}%
\author[5]{Lara Rimmer}%
\author[6]{Matti Jubouri}%
\author[7]{Joseph Coselli}%
\author[3]{Ian Williams}%
\author[1]{Mohamad Bashir}%
\affil[1]{University of South Wales Faculty of Life Sciences and Education}%
\affil[2]{Wrexham Maelor Hospital}%
\affil[3]{University Hospital of Wales}%
\affil[4]{Princess of Wales Hospital}%
\affil[5]{Health Education England North West}%
\affil[6]{Hull York Medical School}%
\affil[7]{Baylor College of Medicine Michael E DeBakey Department of Surgery}%


\vspace{-1em}



  
  \date{May 15, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
\emph{Background:} Initial clinical evaluation (ICE) is traditionally
considered a useful screening tool to identify frail patients during the
pre-operative assessment. However, emerging evidence supports the more
objective assessment of cardiorespiratory fitness (CRF) via
cardiopulmonary exercise testing (CPET) to improve surgical risk
stratification. Herein, we compared both subjective and objective
assessment approaches to highlight the interpretive idiosyncrasies.
\emph{Methods:} As part of routine pre-operative patient contact,
patients scheduled for major surgery were prospectively `eyeballed'
(ICE) by two experienced clinicians prior to more detailed history
taking that also included American Society of Anaesthesiologists score
classification. Each patient was subjectively judged to be either
`frail' or `not frail' by ICE and `fit' or `unfit' from thorough review
of the medical notes. Subjective data were compared against the more
objective validated assessment of post-operative outcomes using
established CPET `cut-off' metrics incorporating peak pulmonary oxygen
uptake ( \emph{V}\selectlanguage{english}O \textsubscript{2PEAK}), \emph{V}\selectlanguage{english}O \textsubscript{2}
at the anaerobic threshold ( \emph{V}\selectlanguage{english}O \textsubscript{2}-AT) and
ventilatory equivalent for carbon dioxide that collectively informed
risk stratification. These data were retrospectively extracted from a
single-centre prospective National Health Service database. Data were
analysed using the Chi-square automatic interaction detection decision
tree method. \emph{Results:} A total of 127 patients examined that
comprised 58 \% male and 42 \% female patients aged 69 \selectlanguage{ngerman}± 10 y with a BMI
of 29 ± 7 kg/m \textsuperscript{2}. Patients were poorly conditioned
with a peak pulmonary oxygen uptake almost 20 \% lower than that
predicted for age, sex-matched healthy controls with 35 \% exhibiting a
\selectlanguage{english}\emph{V}O \textsubscript{2}-AT \textless{}11 mL/kg/min. Disagreement
existed between the subjective assessments of risk with
\textasciitilde{}34 \% of patients classified not frail on ICE were
considered unfit by notes review ( \emph{P} \textless{} 0.0001).
Furthermore, \textasciitilde{}35 \% of patients considered not frail on
ICE and \textasciitilde{}31 \% of patients considered fit by notes
review exhibited a \emph{V}\selectlanguage{english}O \textsubscript{2}-AT \textless{}11
mL/kg/min and of these, \textasciitilde{}28 \% and \textasciitilde{}19
\% were classified as intermediate-to-high risk. \emph{Conclusions:}
These findings highlight the interpretive limitations associated with
the subjective assessment of patient frailty with surgical risk
classification underestimated in up to a third of patients compared to
the validated assessment of CRF. They reinforce the benefits of a more
objective and integrated approach offered by CPET that may help improve
perioperative risk assessment and better direct critical care provision
in patients scheduled for `high-stakes' surgery including open TAAA
repair.%
\end{abstract}%



\sloppy


\textbf{Open Thoracoabdominal Aortic Aneurysm Repair in Cardiopulmonary
Testing Era: A Correlative Cohort Analysis}

Damian M. Bailey\textsuperscript{1}*, Claire L.
Halligan\textsuperscript{2}, Richard G. Davies\textsuperscript{3},
Anthony Funnell\textsuperscript{4}, Ian R. Appadurai\textsuperscript{3},
George Rose\textsuperscript{1}, Lara Rimmer\textsuperscript{5}, Matti
Jubouri\textsuperscript{6}, Joseph S. Coselli\textsuperscript{7,8,9},
Ian M. Williams\textsuperscript{10}, Mohamad
Bashir\textsuperscript{1,10}

\textsuperscript{1}Neurovascular Research Laboratory, Faculty of Life
Sciences and Education, University of South Wales, Pontypridd,
UK;\textsuperscript{2}Department of Anaesthesia, Wrexham Maelor
Hospital, Wrexham, UK; \textsuperscript{3}Department of Anaesthetics,
University Hospital of Wales, Cardiff, UK; \textsuperscript{4}Department
of Anaesthetics, Princess of Wales Hospital, Velindre University NHS
Trust, Health Education \& Improvement Board Wales (HEIW), Wales,
UK;\textsuperscript{5}North West School of Surgery, Health Education
England North West, Manchester, UK; \textsuperscript{6}Hull York Medical
School, University of York, York, UK; \textsuperscript{7}Division of
Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor
College of Medicine, USA; \textsuperscript{8}Department of
Cardiovascular Surgery, Texas Heart Institute, USA
and\textsuperscript{9}Department of Cardiovascular Surgery, CHI St
Luke's Health-Baylor St Luke's Medical Center, Houston, Texas, USA
and\textsuperscript{10}Department of Surgery, University Hospital of
Wales, Cardiff, UK

\textbf{Keywords:} thoracoabdominal; aorta; aneurysm; cardiopulmonary
exercise testing; frailty; fitness

\textbf{Sources of Funding and Conflict of Interest}

This work was supported by a Royal Society Wolfson Research Fellowship
(\#WM170007) and funding from the Higher Education Funding Council for
Wales (to Prof. DM Bailey). Prof. DM Bailey is a member of the
Cardiovascular Network for Wales. Dr. JS Coselli participates in
clinical trials with and/or consults for Terumo Aortic, Medtronic, and
W.L. Gore \& Associates and receives royalties and grant support from
Terumo Aortic. The remaining authors report no disclosures. The authors
have no competing interests to declare.

\textbf{*Correspondence}

Professor Damian M. Bailey PhD FPVRI FRSC FACSM FTPS

Royal Society Wolfson Research Fellow

Professor of Physiology \& Biochemistry

Director of the Neurovascular Research Laboratory

Faculty of Life Sciences and Education

Alfred Russel Wallace Building

University of South Wales

UK CF37 4AT

damian.bailey@southwales.ac.uk

\textbf{Abbreviations}

Cardiopulmonary exercise testing (CPET)

Initial clinical evaluation (ICE)

Peak oxygen uptake (\emph{V} \selectlanguage{english}O\textsubscript{2PEAK})

Ventilatory equivalent for carbon dioxide (\emph{V}
\selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2})

Oxygen uptake efficiency slope (OUES)

Pulmonary oxygen uptake at the anaerobic threshold (\emph{V}
\selectlanguage{english}O\textsubscript{2}-AT)

BMI (body mass index)

FVC (forced vital capacity)

FEV\textsubscript{1} (forced expiratory volume in one second)

ASA (American Society of Anaesthesiologists score)

\textbf{Abstract}

Background: Initial clinical evaluation (ICE) is traditionally
considered a useful screening tool to identify frail patients during the
pre-operative assessment. However, emerging evidence supports the more
objective assessment of cardiorespiratory fitness (CRF) via
cardiopulmonary exercise testing (CPET) to improve surgical risk
stratification. Herein, we compared both subjective and objective
assessment approaches to highlight the interpretive idiosyncrasies.

Methods: As part of routine pre-operative patient contact, patients
scheduled for major surgery were prospectively `eyeballed' (ICE) by two
experienced clinicians prior to more detailed history taking that also
included American Society of Anaesthesiologists score classification.
Each patient was subjectively judged to be either `frail' or `not frail'
by ICE and `fit' or `unfit' from thorough review of the medical notes.
Subjective data were compared against the more objective validated
assessment of post-operative outcomes using established CPET `cut-off'
metrics incorporating peak pulmonary oxygen uptake (\emph{V}
\selectlanguage{english}O\textsubscript{2PEAK}), \emph{V} \selectlanguage{english}O\textsubscript{2} at the anaerobic
threshold (\emph{V} \selectlanguage{english}O\textsubscript{2}-AT) and ventilatory equivalent
for carbon dioxide that collectively informed risk stratification. These
data were retrospectively extracted from a single-centre prospective
National Health Service database. Data were analysed using the
Chi-square automatic interaction detection decision tree method.

Results: A total of 127 patients examined that comprised 58 \% male and
42 \% female patients aged 69 \selectlanguage{ngerman}± 10 y with a BMI of 29 ± 7
kg/m\textsuperscript{2}. Patients were poorly conditioned with a peak
pulmonary oxygen uptake almost 20 \% lower than that predicted for age,
sex-matched healthy controls with 35 \% exhibiting a\selectlanguage{english}\emph{V}
O\textsubscript{2}-AT \textless{}11 mL/kg/min. Disagreement existed
between the subjective assessments of risk with \textasciitilde{}34 \%
of patients classified not frail on ICE were considered unfit by notes
review (\emph{P} \textless{} 0.0001). Furthermore, \textasciitilde{}35
\% of patients considered not frail on ICE and \textasciitilde{}31 \% of
patients considered fit by notes review exhibited a \emph{V}
\selectlanguage{english}O\textsubscript{2}-AT \textless{}11 mL/kg/min and of these,
\textasciitilde{}28 \% and \textasciitilde{}19 \% were classified as
intermediate-to-high risk.

Conclusions: These findings highlight the interpretive limitations
associated with the subjective assessment of patient frailty with
surgical risk classification underestimated in up to a third of patients
compared to the validated assessment of CRF. They reinforce the benefits
of a more objective and integrated approach offered by CPET that may
help improve perioperative risk assessment and better direct critical
care provision in patients scheduled for `high-stakes' surgery including
open TAAA repair.

\textbf{Background}

Traditionally, assessment of fitness for surgery involves a surgeon's
subjective judgement on whether a patient is sufficiently conditioned to
undergo the proposed procedure. Valid and reliable assessment of a
person's functional capacity is thus considered an important component
of preoperative evaluation\textsuperscript{1}. The initial clinical
evaluation (ICE) can be a useful screening tool to identify frail
patients in the pre-operative assessment, despite limited research to
validate implementation. `Frailty' identifies those patients with a
diminished capacity to compensate adequately for external stressors who
are at greater risk of adverse outcomes including a prolonged hospital
stay, institutionalisation, worsening disability and even
death\textsuperscript{2, 3}. It is important to recognize diminished
capacity in patients prior to surgery given that they are less likely to
survive or return to functional status following the physiological
insult of surgery compared to their fitter, more resilient
counterparts\textsuperscript{4}.

ICE almost inextricably requires a clinician to make a rapid decision
concerning the fitness for an operation based on little more than
external appearances. In contrast, preoperative cardiopulmonary exercise
testing (CPET) enhances the integrated risk assessment by providing a
more objective measure to establish if a patient has adequate
cardiorespiratory fitness (CRF) to tolerate major surgery. In support,
CPET has gained popularity as part of the routine preoperative
diagnostic assessment and its predictive value in relation to mid- and
long-term survival in patients undergoing elective open surgical
abdominal aortic aneurysm (AAA) repair is well established including its
ability to forecast postoperative morbidity\textsuperscript{5-7}.

This is especially relevant for open thoracoabdominal aortic aneurysm
(TAAA) surgery, given that it requires careful selection of patients who
will be suitable to undergo extensive surgery and lengthy postoperative
recovery (Figure 1). Predictive risk models have shown that multi-system
impairment is related to negative operative outcomes predisposing to
longer recovery times and increased risk of short- and long-term
mortality and morbidity\textsuperscript{8}. Lung disease, older age,
female sex, New York Heart Association's (NYHA) moderate (III) or severe
(IV) classifications and reduced left ventricular ejection fraction have
been identified as independent risk factors for patients undergoing
proximal aortic repair\textsuperscript{9}. However, there is no singular
metric with the capacity to accurately predict clinical
outcome\textsuperscript{2}.

Thus, it is suspected that patients with poor CRF are especially
vulnerable when faced with the enhanced metabolic demands posed by open
TAAA repair and have an unmet need to better guide patient evaluation,
risk and clearance for surgery. In the coming years when both open and
endovascular options for thoracoabdominal aortic repair are widely
available, there will no doubt be a need to objectively evaluate each
patient to identify the ideal method of surgical repair.

To that end, the present study sought to compare subjective ICE
(`eyeballing') by experienced clinicians against the more objective
validated preoperative assessment using formalised CPET metrics for
patients undergoing major elective surgery. We hypothesized that
subjective assessment would underestimate a patient's `true' surgical
risk, highlighting the benefits of a more integrated objective approach
that has direct relevance for patients scheduled for open TAAA repair.



\textbf{Methods}

\textbf{Ethical approval}

The Cardiff and Vale University Health Board (15/AIC/6352) approved the
retrospective analysis of an anonymised database and thus patient
consent was waived. All procedures were carried out in accordance with
the Declaration of Helsinki of the World Medical
Association\textsuperscript{10}.

\textbf{Design}

Clinical data were extracted from a single-centre (University Hospital
of Wales, UK) prospective National Health Service database for the
purposes of improving perioperative outcomes in patients scheduled for
elective major intra-abdominal surgery over a 12-month period. Data
points were captured using a variety of methods, including medical
record abstraction and formal data collection (below).

\textbf{Clinical assessments}

Demographics

Patient data was gathered from medical notes and recorded by the
clinician conducting CPET and comprised stature, body mass, derivation
of body mass index (BMI) and closed loop flow spirometry.

Subjective assessment

As part of the routine evaluation of patients prior to surgery, patients
were clinically assessed by two experienced clinicians (RGD and IRA) to
determine frailty and fitness for surgery. The clinical evaluation
included the detailed collection of a patient-specific medical history.
This clinical determination aimed to answer the question ``Is this
patient attending for clinical assessment today fit enough for the
proposed surgical procedure?'' Each patient was judged to be either
`frail' or `not frail' after the initial meeting, and this was
supplemented with ``fit'' or ``not fit'' from careful review of their
medical notes. Patients were also graded according to the American
Society of Anaesthesiologists (ASA) grading
criteria\textsuperscript{11}whereby a healthy patient is ASA I, a
patient with mild systemic disease is ASA II, a patient with severe
systemic disease is ASA III, ASA IV refers to a patient with
life-threatening severe systemic disease and ASA V to a moribund
patient.

Objective assessment

CPET: Pre-operative CPET was conducted using an electromagnetically
braked cycle ergometer (Lode, Gronigen, The Netherlands) and a
Medgraphics Ultima metabolic cart (MedGraphics\textsuperscript{TM},
Gloucester, UK) as previously outlined by our group\textsuperscript{7,
12, 13}. Briefly, calibration was undertaken in accordance with the
manufacturer's guidelines using a 3-L volume syringe (Hans Rudolph,
Kansas City, USA) and reference calibration gases. During data
collection, the middle five of seven breaths were averaged. An exercise
protocol was employed requiring patients to cycle at 60 revolutions per
minute for three minutes in an unloaded freewheeling state followed by a
progressively ramped period of exercise (5 to 15 W/min based on mass,
stature, age, and sex) to volitional or symptom limited termination,
followed by three minutes recovery\textsuperscript{14}. Medgraphics
Breeze\textsuperscript{TM}software automatically determined peak oxygen
uptake (\emph{V} \selectlanguage{english}O\textsubscript{2PEAK}) (defined as the highest\emph{V}
\selectlanguage{english}O\textsubscript{2} during the final 30 seconds of exercise reported),
the slope of the relationship between pulmonary ventilation and carbon
dioxide output (\emph{V} \selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2})
and oxygen uptake efficiency slope (OUES). Pulmonary oxygen uptake at
the anaerobic threshold (\emph{V} \selectlanguage{english}O\textsubscript{2}-AT) was manually
interpreted by an experienced clinician using the V-slope
method\textsuperscript{15}, supported by \emph{V}
\selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2}-AT, and \emph{V}
\selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}O\textsubscript{2}-AT.

Risk classification: Each patient was classified with a\emph{V}
\selectlanguage{english}O\textsubscript{2}-AT below (\textless{}) or above (\textgreater{}) 11mL
O\textsubscript{2}/kg/min) based on the seminal works of Weber and
Janicki\textsuperscript{16} and Older et al.\textsuperscript{17} We
further differentiated between low, intermediate and high risk according
to the following criteria:\emph{Low risk} : \emph{V}
\selectlanguage{english}O\textsubscript{2}-AT [?]11 mL/kg/min;\emph{Intermediate risk} : One of:
\emph{V} \selectlanguage{english}O\textsubscript{2}-AT 8-10.9 mL/kg/min, \emph{V}
\selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2}-AT \textgreater{}34,
history of ischaemic heart disease (IHD); \emph{High risk} : \emph{V}
\selectlanguage{english}O\textsubscript{2}-AT \textless{}8 mL/kg/min or [?]two of:\emph{V}
\selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2}-AT \textgreater{}34,
\emph{V} \selectlanguage{english}O\textsubscript{2}-AT \textless{}11 mL/kg/min, history of IHD.

\textbf{Statistical analyses}

Statistical analyses were undertaken using IBM SPSS Statistics for
Windows (Version 27.0, IBM, Armonk, NY, USA). Continuous variables are
reported as mean \selectlanguage{ngerman}± standard deviation (SD). Categorical variables are
reported as frequencies with percentages. Categorical comparisons were
conducted using \selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2} tests and
\selectlanguage{greek}χ\selectlanguage{english}\textsuperscript{2}automatic interaction detection decision tree
method.

\textbf{Results}

\textbf{Patient characteristics}

Table 1 summarises patient characteristics including demographics and
cardiopulmonary performance (spirometry and CPET) with a total of 127
patients examined. Thirty-nine patients (31 \%) were classified as obese
with fifty-six (44 \%) overweight. As anticipated, these patients were
poorly conditioned with a \emph{V} \selectlanguage{english}O\textsubscript{2PEAK} that was on
average almost 20 \% lower than that predicted for age, sex-matched
healthy controls with forty-five patients (35 \%) exhibiting a\emph{V}
\selectlanguage{english}O\textsubscript{2}-AT \textless{}11 mL/kg/min.\emph{V}
\selectlanguage{english}O\textsubscript{2}-AT could not be determined in eighteen patients (14
\%).

\textbf{Clinical risk assessments}

Figure 2 illustrates patient distribution of clinical risk
classification according to assessment method providing a visual of the
(dis) agreements observed complemented by the CHAID decision tree method
analyses summarised in Figures 2-3.

Subjective: There was clear disagreement between the subjective
assessments of risk (ICE-Eyeball (Frailty) compared to Notes Review
(Fitness) with \textasciitilde{}34 \% of patients classified not frail
considered unfit by notes review (Figure 3 A). Equally,
\textasciitilde{}88 \% of patients considered not frail and
\textasciitilde{}82 \% of patients considered fit by ICE (Figure 3 B)
and notes review (Figure 3 C) respectively were classified ASA Grade
II-III (mild to severe disease).

Objective: Subjective assessments generally underestimated patient risk
compared to objective CPET criteria (\emph{V} \selectlanguage{english}O\textsubscript{2}-AT
\textless{}11 mL/kg/min and intermediate-to-high risk). Indeed,
\textasciitilde{}35 \% of patients considered not frail on ICE and
\textasciitilde{}31 \% of patients considered fit by notes review
exhibited a \emph{V} \selectlanguage{english}O\textsubscript{2}-AT \textless{}11 mL/kg/min
(Figure 4 A-B). Of these, \textasciitilde{}28 \% and \textasciitilde{}19
\% (not frail and fit patients respectively) were classified as
intermediate-to-high risk by CPET criteria (Figure 4 C-D).

\textbf{Discussion}

By comparing subjective clinical evaluation of a patient's risk by
experienced clinicians against the more objective validated assessment
of post-operative outcomes via CPET, the present study has identified
two important findings. First, we identified clear disagreement between
subjective assessments of risk with a third of patients classified not
frail considered unfit by notes review and almost nine out of ten
patients suffering from mild to severe disease by ASA classification.
Second, and consistent with our original hypothesis, subjective
assessment underestimated surgical risk in up to a third of patients.
Collectively, these findings highlight the benefits of a more objective
and integrated approach offered by CPET that may help improve
perioperative risk assessment and direct care provision in patients
scheduled for `high-stakes' open TAAA repair.

\textbf{Surgical demands}

Surgery is the third largest cause of death after ischaemic heart
disease and stroke accounting for almost 8 \% of all deaths
globally\textsuperscript{18}. Given the ageing population and projected
burden of vascular arterial occlusive/aneurysmal disease, surgery
remains a major concern for healthcare providers. Importantly, the `high
risk' surgical patient accounts for 13\% of cases yet contributes to a
disproportionate \textgreater{}80\% of all postoperative deaths and
complications\textsuperscript{19}. This is especially the case for TAAA
patients given the extensive repair required and prolonged recovery time
with increasing interest direct towards the `gold-standard' assessment
of CRF via CPET to provide more objective insight into surgical risk
stratification.

An adequate, albeit presently undefined CRF conferring improved
physiological reserve is required in order for a patient to tolerate
extensive open TAAA repair, given that single lung ventilation is
obligatory in order to expose the thoracic aorta following collapse of
the left lung (Figure 1). Acceptable preoperative spirometry assessment
of the pulmonary circulation may consist of an
FEV\textsubscript{1}\textgreater{}1 L and arterial partial pressure of
carbon dioxide \textless{}45 mmHg\textsuperscript{19}. Postoperative
pulmonary complications and reintubation rates of up to 15\% in the
highest volume centres indicate that this remains a major cause of
morbidity following TAAA surgery\textsuperscript{20}. Pulmonary
complications occur in up to 36\% of patients and any adverse lung
function tests preoperatively, highlighted through spirometry and
arterial blood gas analysis, may be advised to undergo a regime
including physical exercise, spirometry training and bronchodilator
therapy\textsuperscript{21}. Other factors reducing prolonged ventilator
support included preservation of the central tendon of the diaphragm by
circumferential division and avoidance of excessive blood
products\textsuperscript{22}. Postoperatively, adequate pulmonary
function is essential for perioperative survival as all patients will be
intubated in the immediate and extensive postoperative recovery phase.

\textbf{Patient co-morbidities}

Importantly, many patients undergoing TAAA repair will have pre-existing
coronary artery disease (CAD) and associated risk
factors\textsuperscript{20}. Significant (but possibly silent) cardiac
disease may reduce patient tolerance of thoracic aortic cross-clamping,
an obligatory procedure that immediately increases afterload, and left
ventricular stress, upon the heart\textsuperscript{21}. Oxygen
deprivation in proximal tissues and sympathoadrenal discharge constricts
arterioles and is typically accompanied by arteriovenous shunting.
Whilst acute (CPET) exercise may not replicate the profound
physiological challenges imposed by cross-clamping, assessing the
patient's body under `simulated' (physical) stress and corresponding
systemic response to microcirculatory hypoxaemia may determine how well
systemic tissue perfusion adapts to the surgical insult.

Furthermore, there is mounting evidence that the risk of developing
spinal cord ischaemia is increased by up to 80\% in those with
CAD\textsuperscript{23}. Identification of disease may not negate
surgery but may lead to optimisation by coronary artery stenting or
instigating antiplatelet therapy prior to any planned
procedure\textsuperscript{21, 24}. Connective tissue disorders represent
an additional major risk factor for thoracic aortic disease with up to
20\% of patients expressing at least one `high-risk'
gene\textsuperscript{25}. Marfan syndrome (MS) is one such genetic
disorder and typically presents in younger patients\textsuperscript{26}.
Giske et al. focused on pulmonary function and rehabilitation in
patients with MS and found that \emph{V} \selectlanguage{english}O\textsubscript{2PEAK} was 30\%
and 50\% lower in females and males respectively, compared to healthy
(non-MS) controls\textsuperscript{27}.

\textbf{TAAA surgery and CPET}

While there is clear justification for the integration of CPET into
perioperative risk assessment for open TAAA, there are surprisingly few
studies in the published literature. Hornsby \emph{et al} . used CPET
postoperatively only to assess exercise tolerance following open TAAA or
type A dissection repair\textsuperscript{28}. CPET was analysed
retrospectively or performed three months following open repair and
identified that (median) \emph{V} \selectlanguage{english}O\textsubscript{2PEAK} was reduced by
36\% after type A aortic dissection repair. This highlights the critical
increase in metabolic demand driven by the need to increase vascular
O\textsubscript{2} delivery to support the additional cellular
bioenergetic demands incurred by surgery to ensure successful
recovery\textsuperscript{29}. If the patient is unable to fulfil this
metabolic demand (i.e. CRF is inadequate), the physiological `insult'
posed by TAAA surgery can subsequently lead to O\textsubscript{2} debt
that can overwhelm the patient and result in organ failure and
death\textsuperscript{30}.

In the present study, we chose to differentiate between those patients
with and without `adequate' CRF based on the `cut-off' metrics
originally established by Weber and Janicki\textsuperscript{16} in heart
failure patients and later implemented by Older et
al.\textsuperscript{17} specifically \emph{V} \selectlanguage{english}O\textsubscript{2}-AT
\textless{} (unfit) or \textgreater{} (fit) 11 mL/kg/min. Older et
al.\textsuperscript{17} identified an 18\% mortality rate in elderly
surgical patients considered unfit by this threshold compared to 0.8\%
in fit patients. We further categorised patients based on CPET risk
through additional implementation of complementary biomarkers
including\emph{V} \selectlanguage{english}O\textsubscript{2} peak \textless{}15 mL/kg/min
and\emph{V} \selectlanguage{english}\textsubscript{E}/\emph{V} \selectlanguage{english}CO\textsubscript{2}-AT
\textgreater{}34 given their combined ability to distinguish the
`at-risk' patient and better predict post-operative survival following
AAA surgery\textsuperscript{31}. However, it is important to emphasise
that ongoing research continues to better define threshold metrics to
further optimise risk prediction models and this is especially relevant
for TAAA patients given the magnitude of the surgical `hit' encountered.
Furthermore, CRF (and corresponding risk) stratification needs to be
based not on a single binary cut-off but rather a range of values for
any given dynamic CPET metric given the inherent (and extensive)
biological variation\textsuperscript{13} and this remains to be
established for the `high-stakes' TAAA patient.

Importantly and in stark contrast to the present study, none of these
researchers have reported the clinician's initial views prior to
surgery. There are understandable if not unavoidable limitations to what
a clinician might gain from the very first review of a patient, often
without a thorough knowledge of past medical history. Initial
information is oftentimes dictated by loose `impressions' of cognitive
function, body habitus, strength of handshake and general nutritional
status\textsuperscript{32}. Our findings highlight that ICE is indeed
unreliable compared to CPET metrics with the danger of underestimating
patient risk. This has implications when determining the appropriate
level of postoperative care after TAAA surgery notwithstanding the
potential for medico-legal complications.

Clinical assessment from the end of the bed will undoubtedly benefit
from more comprehensive physiological testing. This is particularly the
case for increasing numbers of patients with TAAA who are considered for
endovascular rather than open surgery\textsuperscript{33}. It is likely
in the future treatment plans will incorporate both open and
endovascular approaches for intervention and this may even be
incorporated in a staged manner\textsuperscript{34}.

\textbf{Conclusions}

These findings highlight the interpretive limitations associated with
the subjective assessment of patient frailty with surgical risk
classification underestimated in up to a third of patients compared to
the more objective validated assessment of post-operative outcomes via
CPET-derived CRF. For `high-stakes' open TAAA surgery, the integration
of CPET can improve perioperative risk assessment though further
research is required to identify `lower limits' of CRF below which
operative intervention may be considered prohibitively risky. Surgeons
also need to consider (pre-operative) exercise training as a modifiable
component of multimodal prehabilitation strategies with the potential to
augment CRF, reduce surgical risk and thus improve outcome.

\textbf{Acknowledgements}

The authors thank Susan Y. Green MPH for input.

\textbf{Author's Contributions}

All authors read and approved the final manuscript.

\textbf{Availability of data and materials}

The data sets used and analysed during the study are available from the
corresponding author upon request.



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\textbf{Table 1. Patient characteristics}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Demographics &\tabularnewline
\midrule
\endhead
Sample size (n) & 127\tabularnewline
Male (n/\%):Female (n/\%) & 74/58:53/42\tabularnewline
Age (y) & 69 \selectlanguage{ngerman}± 10\tabularnewline
BMI (kg/m\textsuperscript{2}) & 29 \selectlanguage{ngerman}± 7\tabularnewline
Spirometry &\tabularnewline
FVC (\% predicted) & 95 \selectlanguage{ngerman}± 19\tabularnewline
FEV\textsubscript{1} (\% predicted) & 92 \selectlanguage{ngerman}± 22\tabularnewline
FEV\textsubscript{1}/FVC (\% predicted) & 73 \selectlanguage{ngerman}± 9\tabularnewline
CPET metrics &\tabularnewline
Peak workload (W) & 95 \selectlanguage{ngerman}± 43\tabularnewline
Peak workload (\% predicted) & 85 \selectlanguage{ngerman}± 29\tabularnewline
\selectlanguage{english}\emph{V}O\textsubscript{2PEAK} (mL/kg/min) & 17.8 \selectlanguage{ngerman}± 5.2\tabularnewline
\selectlanguage{english}\emph{V}O\textsubscript{2PEAK} (\% predicted) & 81 \selectlanguage{ngerman}± 20\tabularnewline
\selectlanguage{english}\emph{V}\textsubscript{E} /\emph{V}\selectlanguage{english}CO\textsubscript{2} slope (AU) & 34 \selectlanguage{ngerman}±
6\tabularnewline
OUES {[}(mL/min O\textsubscript{2})/ (L/min
\selectlanguage{english}\emph{V}\textsubscript{E}){]} & 1729 \selectlanguage{ngerman}± 490\tabularnewline
\selectlanguage{english}\emph{V}O\textsubscript{2}-AT \textgreater{}11 mL/kg/min (n/\%) &
64/50\tabularnewline
\emph{V}\selectlanguage{english}O\textsubscript{2}-AT \textless{}11 mL/kg/min (n/\%) &
45/35\tabularnewline
\emph{V}\selectlanguage{english}O\textsubscript{2}-AT indeterminate (n/\%) &
18/14\tabularnewline
\bottomrule
\end{longtable}

Values are mean \selectlanguage{ngerman}± SD; BMI, body mass index; FVC, forced vital capacity;
FEV\textsubscript{1}, forced expiratory volume in one second;\selectlanguage{english}\emph{V}
O\textsubscript{2PEAK}, peak pulmonary oxygen uptake;\emph{V}
\selectlanguage{english}\textsubscript{E} /\emph{V} \selectlanguage{english}CO\textsubscript{2,} ventilatory equivalent
for carbon dioxide; OUES, oxygen uptake efficiency slope;\emph{V}
\selectlanguage{english}O\textsubscript{2}-AT, pulmonary oxygen uptake at the anaerobic
threshold.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1. Anatomical aspects and surgical approach to extent II
thoracoabdominal repair.}

A. The chest is entered through the sixth intercostal space. Left medial
visceral rotation and circumferential division of the diaphragm enable
exposure of the entire thoracoabdominal aorta. B. Left heart bypass
(LHB) is commonly used to offload the heart from stressors of aortic
surgery; LHB is initiated by placing a cannula in the left atrium via a
left inferior pulmonary venotomy and then connecting it to the drainage
line of the LHB circuit. After initiation, the proximal aortic clamp is
placed. The distal aortic clamp is placed across the mid-descending
thoracic aorta. The aortic segment between the two clamps is opened
longitudinally using electrocautery. A stand-alone circuit to provide
cold renal perfusion is prepared for later use. C. Following completion
of the proximal anastomosis, the aorta is opened longitudinally to the
aortic bifurcation. Crucial intercostal and lumbar arteries are
reattached. Cold renal perfusion and selective visceral perfusion are
provided to protect the visceral organs.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 2. Differences in clinical risk classification according
to patient assessment method.}

ICE, initial clinical evaluation; (\emph{V} \selectlanguage{english}O\textsubscript{2}-AT)
pulmonary oxygen uptake at the anaerobic threshold during
cardiopulmonary exercise testing; ASA, American Society of
Anaesthesiologists score (ASA I, normal healthy, ASA II, mild systemic
disease, ASA III, severe systemic disease).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 3.} \textbf{Comparison between different subjective
methods of patient risk assessment.}

ASA, American Society of Anaesthesiologists score (ASA I, normal
healthy, ASA II, mild systemic disease, ASA III, severe systemic
disease).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Figure 4. Comparison of subjective assessment of patient risk
(initial clinical evaluation (ICE) of frailty and notes-review of
fitness) against risk defined by objective cardiopulmonary exercise
testing (CPET) metrics.}

\emph{V} \selectlanguage{english}O\textsubscript{2}-AT, pulmonary oxygen uptake at the anaerobic
threshold. See Methods for definition of low, intermediate and high
risk.

\selectlanguage{english}
\FloatBarrier
\end{document}

