Peripheral Artery Disease

INTRODUCTION
Cardiogenic shock (CS) complicates up to 10% of patients presenting with acute myocardial infarction
(AMI), with one-third of those
affected not surviving to hospital discharge.1 Given its shared risk factors with coronary artery disease
(CAD), peripheral artery disease (PAD) is often seen in patients presenting with AMI.2 Over the past
decade, admissions for PAD have increased in the United States, accompanied by persistent high rates
of morbidity and mortality.3 Patients presenting with CS from AMI carry the highest risk of mortality when
undergoing percutaneous coronary interven- tions (PCI), but they may also bear the greatest benefit
from intervention.4 Those with comorbid PAD may represent a particularly high-risk group, potentially
because of higher atherosclerotic burden and vascular access limitations for revascularization. However,
no data are available on the outcomes of patients presenting with CS from AMI with comorbid PAD. To
this end, in this issue of the Journal of the American College of Cardiology, Mihatov et al5 explore the
morbidity and mortality associated with PAD among patients presenting with AMI and CS.
In this study, the authors used data on 71,690 Medicare fee-for-service beneficiaries aged $65 years
hospitalized with AMI and CS, in whom 5.9% had a diagnosis of PAD
The authors found that in addition to carrying a greater burden of cardiovascular condi- tions and risk factors,
patients with PAD were less likely to have percutaneous or surgical revasculariza- tion. Patients with PAD
experienced higher adjusted mortality rates, both in-hospital and out-of-hospital, compared with patients without
PAD. In addition, patients with PAD were at greater risk of facing am- putations and bleeding, and needing lower
extremity revascularization while as an inpatient and during follow-up. Not unexpectedly, patients with PAD were
less likely to be treated with mechanical circulatory support (MCS), but when used, patients with PAD had higher
risk of mortality, amputation, and lower ex- tremity revascularization. The authors should be congratulated on their
use of a large and complete dataset to examine this important clinical question.
However, a major limitation of the current study is establishing causality between PAD and the findings of poor
outcomes. Is it possible that patients with PAD had less revascularization and worse outcomes because of more
advanced atherosclerotic and co- morbid disease? Clearly, in looking at Table 1, those with PAD had significantly
higher rates of atrial fibrillation, chronic kidney disease, chronic obstruc- tive pulmonary disease, congestive heart
failure, and diabetes. Was it a conglomerate of these factors that contributed to lower revascularization and worse
inpatient and outpatient outcomes? Although the authors accounted for many of these in their multi- variable
regression analysis, there are important fac- tors that were not measured in this study that are known to influence
treatment decisions and out- comes, including frailty, mental status, cardiac arrest presentation, and surgical
eligibility.4 Furthermore, having used only a Medicare fee-for-service popula- tion, its findings can be extrapolated
only to older patients who may be less likely to be treated aggres- sively, either with revascularization or MCS,
given
advanced severe illness, multiple comorbidities, or patient preferences. Another major limitation is se-
lection bias. The diagnosis of PAD was established based on billing codes, most likely identifying those
with symptomatic and advanced PAD. These patients represent a group at higher risk for cardiovascular
events and limb loss compared with those with less severe or subclinical PAD.
PAD continues to be recognized in prior and recent research to carry a high rate of morbidity and mor-
tality, being truly the old and new silent killer. Pa- tients presenting with stable CAD or AMI who have a
concurrent diagnosis of PAD are at greater risk of mortality, reinfarction, stroke, bleeding, and heart failure
compared with those without PAD.6 When patients with PAD present with AMI, they often have more
advanced CAD, with higher rates of multivessel involvement, including left main disease, and higher rates
of surgical revascularization during AMI hospi- talization.6 In patients undergoing PCI, the presence of PAD
was independently associated with higher mortality rates during short- and long-term follow-up compared
with patients without PAD.7 Similarly, the presence of PAD is associated with greater incidence of stroke,
renal failure, and limb ischemia following coronary artery bypass graft.8 In addition, in patients undergoing
trans-aortic valve replacement (TAVR), PAD was associated with a higher incidence of death, readmission,
bleeding, and myocardial infarction compared with those without PAD.9 Clearly, the in- dependent
association between PAD and cardiovas- cular outcomes is irrefutable and has been well established. So
how does the current contribution by Mihatov et al5 help us
The minimally invasive percutaneous treatment of cardiovascular and interventional management of coronary, valvular,
and vascular disease has signifi- cantly evolved in the past decade. Large-bore access, which was previously relegated to
vascular surgeons for endovascular aortic interventions, is now commonplace in the cardiac catheterization labora- tories
and among interventional cardiologists. Thanks to the clinical advances in heart failure, TAVR, and changes in transplant
listing criteria, in conjunction with advances in devices for MCS, pa- tients who were not candidates for lifesaving in-
terventions are now being treated across the United States in many medical centers. However, these ad- vances have
come at a cost. Vascular complications, including high rates of vessel injury, re- vascularizations, and amputations, remain
the num- ber one limitation of MCS, TAVR, and even for aortic
Shishehbor and Castro-Dominguez 1237 Peripheral Artery Disease
interventions.10-12 Strategies that can address PAD and associated vascular complications could poten- tially address
disparities in revascularization and significantly reduce complications, including ampu- tation, in this population. Probably
the most impor- tant strategy to reduce complications is the early identification of PAD and its extent followed by a
multidisciplinary approach for patients requiring advanced interventions. Early integration of vascular specialists who can
help assess the degree of PAD severity, and inform potential strategies or in- terventions that could facilitate
revascularization or MCS initiation, as well as reduce the risk of limb loss, is crucial. Furthermore, dedicated training of
inter- ventional cardiologists in proper vascular assess- ment, careful techniques for large-bore access and closure, and
prompt recognition and management of access-related complications will only help improve the care of patients with PAD
requiring complex in- terventions for coronary, valvular, and heart failure therapies. Technical advances, such as external
antegrade perfusion or alternative access sites that require vascular expertise, will also provide different management
options for patients with cardiovascular diseases requiring intervention.
Importantly, we need to identify PAD and prevent disease progression. PAD overall remains
under- diagnosed, even in patients at high risk of cardio- vascular events. In patients aged >65
years and in those with diabetes and other risk factors for atherosclerosis, PAD screening may
help identify a subgroup of patients at especially high risk of adverse cardiovascular outcomes
who might benefit from more intensive secondary prevention and surveil- lance. Furthermore,
PAD remains undertreated, despite evidence that guideline-directed medical therapy in patients
with symptomatic PAD is associ- ated with reduction in cardiovascular events, limb events, and
mortality.13
Patients with AMI complicated with CS carry a high risk of mortality but may also benefit the
most from potentially lifesaving interventions such as revascu- larization and MCS.
Understanding how comorbid PAD can alter a patient’s risk profile is crucial to be able to deliver
the most appropriate therapies and specialized management. Indications for complex and
large-bore interventions will continue to in- crease, while advances in techniques and devices
will similarly evolve. Only with an interdisciplinary approach using expertise across different
disciplines will we be able to reduce morbidity and mortality in this high-risk population with
PAD.