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19 Health-Related Quality of Life Outcomes for Endovascular and Open Surgical Interventions…
401
endovascular repair of aortic bifurcation
(CERAB) to conventional aortoiliac bypass.
There is also a relative paucity of studies evaluating HRQOL outcomes of surgical bypass compared to the number of endovascular studies.
The reasons for poor HRQOL outcomes following endovascular intervention or surgery
remain poorly understood, but are likely complex
and multifactorial. Procedure-related outcomes
of interventions including failed revascularisation and lesion recurrence may contribute to poor
HRQOL outcomes [54, 55]. However, as mentioned, the relationship between primary patency
and HRQOL has not been denitively demonstrated. Equally, whilst there is some suggestion
that avoidance of major limb amputation by
means of revascularisation may lead to improved
HRQOL, other studies have demonstrated that
HRQOL can signicantly improve after amputa-
tion because of an elimination of pain, as well as
CLTI induced complications such as ulceration
and infection [56, 57]. HRQOL outcomes following amputation were also found to be dependent on several patient factors, including family
support and age. Patient factors may also contribute to poorer HRQOL outcomes following revascularisation interventions; type D personality
(i.e. tendency towards negative affectivity) and
baseline frailty have both been demonstrated to
be associated with worse HRQOL outcomes [58,
59]. Socioeconomic deprivation has been shown
to negatively impact clinical outcomes and may
also play a role in HRQOL [60]. Further research
to better understand patient-related predictors of
poor HRQOL outcomes is necessary to guide
appropriate patient selection. An overview of
possible predictors of poor HRQOL outcomes
following intervention is presented in Fig.19.2.
Patient Factors (Physical)
• Co-morbidities
• Cardiovascular Risk
• Background Frailty
Procedure Factors
• Failure to revascularize
• Restenosis/reocclusion
Fig. 19.2 Possible predictors of poor HRQOL outcomes following surgery and intervention for peripheral vascular
disease
Patient Factors (Psychosocial)
• Type D Personality
• Socioeconomic status
Predictors of poor
quality of life post
intervention or
surgery

402
Highlighted Conclusions
• The approach to measuring HRQOL outcomes in existing studies is inconsistent and
both for research and clinical practice
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Fig. 19.3 Highlighted
conclusions
J. K. Tun et al.
• There is increasing recognition for the need to assess HRQOL outcomes following
invasive interventions for peripheral arterial disease.
• In general, invasive interventions for aortoiliac and femoropopliteal steno-occlusive
artery disease can lead to an improvement in HRQOL outcome
• Due to issues with research methodology, the inferences that can be drawn from
current research in HRQOL outcomes are limited.
highly variable.
• Further research is required to determine how best to measure HRQOL outcomes
Recent developments and trends in conducting “big data” research by mining data collected
through routine clinical care may hold great
potential for HRQOL research in PAD intervention. Such an approach would provide a large
volume of data from real-world practice and may
overcome some of the limitations observed in
existing RCTs and cohort studies previously
mentioned. To facilitate this big data research, it
is important for vascular clinicians to adopt evaluation and standardised documentation of
HRQOL measures into routine clinical practice.
In this systematic review, we purposefully
identied studies which where specic to predened anatomical segments, i.e. aortoiliac and
femoropopliteal. However, as a result, we
excluded many studies which included interventions across different anatomical segments and
did not provide segment specic sub-analysis of
the results; this is a potential limitation to this
review.
In conclusion (Fig. 19.3), this systematic
review demonstrated that in general, invasive
interventions for aortoiliac and femoropopliteal
steno-occlusive artery disease can lead to an
improvement in HRQOL outcomes. However,
the possibility to ascertain further clinically
meaningful inferences are limited due to the clear
methodological constraints within the current literature. Perhaps the most pertinent limitations
are that HRQOL are often secondary outcome
measures and therefore likely to lack statistical
HRQOL tools also make it impossible to compare outcomes of different studies. To overcome
these limitations, adequately powered studies,
along with a standardised approach to measuring
HRQOL outcomes, is required to improve the
quality of future research and allow more patientcentric decision making.
Appendix: Scoring Criteria toAssess
Methodological Quality ofIncluded
Papers
• Socio-demographic and medical data are
described (e.g. age, race, etc.)
• Inclusion and/or exclusion criteria are
formulated
• The process of data collection is described
(e.g. interview or self-report)
• The results are compared between two groups
or more (e.g. healthy population groups with
different treatment or age)
• Participation and response rates for patient
groups must be described as >75%
• Information is presented about patient/disease
characteristics of respondents and
non-respondents
• A standardized or valid QOL questionnaire is
used
• Results are not only described for QOL but
also for the physical, psychological and social
domains

19 Health-Related Quality of Life Outcomes for Endovascular and Open Surgical Interventions…
403
• Mean, median, standard deviations or percentages are reported for the most important outcome measures
• Patients signed an informed consent form
before study participation
1 point is awarded for each criterion met.
Maximum achieveable score = 10.
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Infrapopliteal Arteries (Classical
andPercutaneous)
RichardAnthonyMeena andOlamideAlabi
20
The Emergence andImportance
ofQOL andPROMS forPeripheral
Artery Disease
Peripheral artery disease (PAD) is dened by
chronic, atherosclerotic disease in arterial beds
outside of the heart or brain. Arterial occlusive
disease of the lower extremities is the third most
common manifestation of systemic atherosclerosis behind heart disease and stroke, and this condition affects over ten million cases nationwide
and over 200 million people worldwide [1]. Risk
factors associated with PAD include multiple
standard cardiovascular risk factors including
tobacco abuse, diabetes mellitus, hypertension,
dyslipidemia, hyperhomocysteinemia, male sex,
age, and renal insufciency. PAD manifests along
a clinical spectrum from asymptomatic patients
to tissue loss in the foot and carries a signicant
risk of cardiovascular morbidity and mortality.
This condition is associated with three times the
average risk of cardiovascular events and mortality [2] and carries a high risk for major amputation with over 185,000 major amputations taking
R. A. Meena · O. Alabi (*)
Division of Vascular Surgery and Endovascular
Therapy, Department of Surgery, Emory University
School of Medicine, Atlanta, GA, USA
e-mail: richard.meena@emory.edu;
olamide.alabi@emory.edu
place each year in the United States [3]. The
prevalence of PAD in the general population
increases dramatically with age [4], and the number of interventions provided to those with PAD
has demonstrated a steady increase over time [5].
As more patients with PAD present to vascular
specialists for medical attention, the necessity
and timing of intervention(s) have become a topic
of important inquiry. Lower extremity revascularization is often a temporizing measure because
established goals include symptom improvement
or resolution, wound healing, and limb preservation; however, there are no curative medical or
surgical therapies available to date. Given the signicant morbidity associated with vascular interventions and sequelae of potentially poor
outcomes, vascular specialists are faced with
even more complex decisions when formulating
a plan of care for patients with PAD.
Whether or not to intervene on a patient with
signicant lower extremity PAD can be a difcult
decision to make. Traditionally, outcomes such
as revascularization patency, readmission, limb
loss, and mortality are frequently reported after
lower extremity revascularization [6–8].
Although these outcomes are critical metrics to
evaluate after operative intervention, for the
interventionalist and healthcare system, they do
not always embody what the individual patient
values most. Therefore, providers have begun to
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T. Athanasiou et al. (eds.), Patient Reported Outcomes and Quality of Life in Cardiovascular Interventions,
https://doi.org/10.1007/978-3-031-09815-4_20
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Predictors of poor quality of life
Low or borderline ABI(12)
Tissue loss(13)
Rest pain(13)
Poor cognitive status(14)
Lack of therapeutic options(15)
Fig. 20.1 Predictors of poor quality of life in patients with peripheral artery disease
incorporate patient-reported outcome measures
(PROMS), including quality of life (QoL) assessments, as part of their decision-making algorithm. In the 1960s and 1970s, clinicians began to
use QoL assessments to evaluate the utility of
new technologies in patient care [9]. Vascular
interventionalists paralleled medicine as a whole
been associated with lower quality of life endpoints [13]. Finally, poor cognitive status in
patients with peripheral artery disease may further lead to a worse quality of life [14]. These
known risk factors serve as a foundation on
which providers can tailor care discussions with
their patients.
in that early QoL metrics centered on cost effectiveness, such as quality-adjusted life years
(QALYs). For example, a landmark vascular
trial, Asymptomatic Carotid Artery Stenosis
Assessing QoL andPROMS
inPeripheral Artery Disease
(ACAS), was re-analyzed under the scope of
QALYs in 1997 [10]. Since 2000, these analyses
extend far beyond cost effectiveness and have
begun to incorporate patient-reported outcomes
as guidance to proceed with and/or defer specic
vascular interventions for some patients.
Measuring QoL on a larger scale has been
shown to directly impact clinical medicine.
Norman et al. demonstrated that minimally
important difference estimates for QoL assessments only approach half a standard deviation.
Therefore, even small shifts in QoL metrics could
signicantly impact patient care [11].
Several studies have suggested certain factors
that may predispose patients to a lower quality of
life in peripheral artery disease (Fig.20.1). Lower
ankle-brachial index alone has been associated
with worse patient-reported outcome measures
[12]. Chronic limb-threatening ischemia, as
dened as rest pain or tissue loss, further has
In both the intermittent claudication (IC) and
chronic limb threatening ischemia (CLTI) populations, intervention has not clearly demonstrated
improved or worsened QoL.This is in large part
due to the non-binary nature of QoL measurements. As QoL has become an increasingly
important topic of research, particularly with
such a morbid disease process and overwhelmingly elderly patient population, great strides
have been made to qualify these shades of gray,
rather than black-and-white, outcomes.
Questionnaires have long been the primary
tool used to assess QoL in surgical research, as
they allow patients to express their opinions
while maintaining a standard form from which
researchers can capture data. Created in the late
1980s, the 36-item Short Form Health Survey
(SF-36) sought to capture adult patients’ perceptions regarding their health and wellbeing. This
Wu A, et al.
Duff S, et al.
Duff S, et al.
Gardner AW, et al.
Sprengers RW, et al.

20 Infrapopliteal Arteries (Classical andPercutaneous)
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instrument assesses eight domains, including
physical function as it relates to one’s health,
limitations related to physical and emotional concerns, social functioning, bodily pain, and general and mental health; the instrument has since
been validated in the general population and general chronic disease states [16]. The European
Quality of Life 5 Dimension scale (EQ-5D) similarly uses domains to assess quality of life in a
general population. This tool’s prior iteration, the
EuroQol instrument, was found to have relatively
poor validity when compared to the SF-36 and
with evidence of being less sensitive at the ceiling [17]. The instrument was further rened to a
ve-domain scale, the EQ-5D.EQ-5D domains
include assessment of mobility, self-care, usual
activities, pain/discomfort, and anxiety/depression. Clearly, patterns can be appreciated when
comparing SF-36 and EQ-5D; physical and mental health, as well as “usual activities” and pain,
all can be drawn from when assessing general
QoL in health care.
Though useful, both SF-36 and EQ-5D are
fairly generic tools used to assess a general population regarding QoL.The ability to provide such
generalizable results is undoubtedly why these
questionnaires have become so useful in health
services research. However, it became evident
that tools specic to PAD would provide a more
appropriate assessment in this population. The
Vascular Quality of Life questionnaire (now
referred to VascuQoL-25) captures data using a
25 question review of ve domains—symptoms,
pain, activities, social life, and emotional state—
and a 7-point response scale [18]. When comparing the generalized questionnaires and
VascuQoL-25 in the assessment of patients suffering from PAD, de Vries etal. suggested that
the VascuQoL-25 should become the primary
questionnaire when creating any future studies
evaluating QoL in PAD given that this instrument
provides a better description of the unique struggles vascular patients with chronic conditions
experience daily [19].
Over time, it became evident that patient compliance with lengthy questionnaires was not sustainable. In the PREVENT III trial, for example,
patient compliance with questionnaires was doc-
umented to decline signicantly over time, from
92% at the start of the study, to 61% at 3months,
and ultimately to 52% at 1year [20]. To combat
patient fatigue with questionnaires yet still
obtaining accurate disease-specic measurements of QoL, these lengthy questionnaires have
been modied. VascuQoL-25 has been limited to
VascuQoL-6, cutting the length of the questionnaire by nearly 75% [21].
Measurement of QoL in those who suffer
from vascular disease is extremely important
given associated burden including severe symptoms, high morbidity either from their chronic
disease state, risk of limb loss, and/or death,
resource utilization from family members and
healthcare facilities, and nancial costs associated with their care. Over the years, clinicians
have struggled with determining the best intervention, if any, for patients suffering from PAD
just as investigators have attempted to rene their
methods of assessing vascular intervention quality and outcomes. What has traditionally been
lacking in the literature is the voice of the patient
and what matters most to them and their families.
Many have met this charge with beginning to
describe and better understand how patients with
PAD view the quality of the lives they lead with
or without PAD intervention.
QoL andPROMS inIntermittent
Claudication (IC)
Patients with IC have a signicantly reduced
QoL. In a 1995 multicenter study from the
Scottish Vascular Audit Group, 201 patients with
IC completed SF-36 health status questionnaires
and, compared to the general population, had
worse QoL in all domains [22]. Severity of disease, dened as walking distance prior to onset of
symptoms, was a signicant predictor of all
parameters except mental and emotional wellbeing, as per QoL evaluations with the SF-36 form.
The authors recommended that for IC, the goal
should be improved QoL; therefore, use of these
QoL assessments in clinical practice (as opposed
to just within the connes of research) may assist
PAD interventionalists in their decision making

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R. A. Meena and O. Alabi
with the PAD patient with IC.Malgor etal. published a systematic review compiling data on
treatment in patients with intermittent lower
extremity claudication symptoms [23]. They concluded that both endovascular and open intervention as well as exercise therapy improved QoL
compared to medical management alone. They
also acknowledged that procedures can beget
complications and many procedures have limited
long term durability in this population.
Multiple randomized controlled trials, such as
the OBACT trial, MIMIC, and others, have compared the benet of intervention in the setting of
IC and included QoL comparisons in their cohorts
[24–26]. The MIMIC trial reviewed 93 patients
with IC on best medical therapy and participating
in a supervised exercise program [25]. They were
enrolled to a treatment arm with percutaneous
transluminal angioplasty (PTA) versus no
PTA. Using the SF-36, they found that those
enrolled in the PTA treatment arm did not demonstrate improvement in QoL compared to no
PTA.This was dissimilar to the CLEVER trial in
that stent angioplasty conferred an improvement
in reported QoL compared to supervised exercise
programs [27]. Given IC as the symptomatology
at the time of presentation in these studies, the
majority of these interventions are targeting vessels above the level of the knee. Thus, while it is
important to understand the body of literature
regarding QoL effects after lower extremity
revascularizations, this is not the focus of this
chapter. As well, OBACT, a single center study
following patients with IC for 2years and used
the SF-36 as well as CLAU-S (a claudication specic QoL questionnaire), found that patients with
IC undergoing early peripheral intervention with
medical therapy compared to patients on optimal
medical therapy alone, had improved functional,
hemodynamic, and QoL outcomes [24].
QoL andPROMS inChronic LimbThreatening Ischemia (CLTI)
Chronic limb-threatening ischemia (CLTI) represents the most severe manifestation of lower
extremity PAD. The TransAtlantic Inter-Society
Consensus for the Management of Peripheral
Artery Disease (TASC II) guidelines dene as
chronic ischemic rest pain or ischemic skin
lesions. CLTI is associated with signicant morbidity and mortality [2]. Due to the associated
burden of high morbidity with or without intervention, high resource utilization, and associated
excess healthcare costs, investigators have now
begun to look toward patient-reported outcome
measures (PROMs) and QoL measures early on
when determining an appropriate plan of care for
these patients.
Initial studies regarding QoL after LE open
surgical bypass reviewed patients’ pre- and postoperative functional status. In 1996, AbouZamzam et al. reviewed functional status after
infrainguinal bypasses [28]. Five hundred thirteen patients in this patient underwent infrainguinal bypass at a single center over 15years. All
included patients had ischemic rest pain or tissue
loss and over 90% of the patients reviewed had a
distal bypass target below the level of the knee.
Of those patients who ambulated with assist
devices preoperatively, 97% were found to maintain this level of function at 6months postoperatively. Independent living status was assessed; of
those patients living independently preoperatively, 99% maintained their independence at
6 months after surgery. A similar review of
patients with CLTI retrospectively looked at 334
patients who underwent 419 infrainguinal
bypasses at two institutions over a 7-year period
[29]. Sixty-two percent of these bypasses had a
distal target located below the knee. Limb salvage was reported as 85% at 1year, with only a
6% drop over the course of the next 2years; however, the authors emphasized that one-quarter of
their patients had not achieved wound healing at
1year, nearly one-fth had lost ambulatory status, and 5% were no longer living independently.
These studies clearly demonstrate the juxtaposition of excellent provider-specic outcomes
alongside poor/failing PROMs.
Markers of functional status, including independent living and ambulatory status, are not
age-independent, as increasing age certainly
impacts both the pathophysiology underlying
CLTI and the potential risk of morbidity and
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