Stroke
Stroke is by far the most clinically important and well-studied perioperative neurological
complication after cardiac procedures. In general, stroke is considered to be perioperative
if occurring within 30 days from the procedure.[1]
[2]
Incidence
The reported incidence of perioperative stroke varies according to the type of procedure
([Table 1]). Stroke occurs in 1.1 to 4.1% of patients undergoing coronary artery bypass graft
(CABG) and 0.1 to 0.5% of those undergoing PCI.[1]
[2]
[3]
[4]
[5] While many large prospective and observational studies have demonstrated that periprocedural
stroke rates are lower following PCI compared with CABG,[1]
[2] the literature is less robust for complication rates from valvular repair and replacement
procedures. Registry studies of both CABG and PCI from the 2000s have reported lower
incidences of periprocedural stroke compared with similar studies from the two preceding
decades.[2]
[5]
[6] However, some prospective and retrospective studies have shown either stable or
even increasing rates of periprocedural stroke from the mid-1990s to the 2000s, with
authors hypothesizing that advances in procedural technique are offset by the increasing
proportion of high-risk patients being considered eligible for surgery.[1]
[4] In interpreting incidence data for perioperative stroke, one must keep in mind the
high degree of heterogeneity in study type, the authors' definition of stroke, and
the method of ascertainment of stroke occurrence.
Table 1
Incidence of stroke at 30 days by type of procedure
|
Procedure type
|
Procedure
|
Incidence of periprocedural stroke (%)
|
|
Surgical
|
Isolated CABG
|
1.1–4.1[1]
[2]
[3]
[4]
|
|
Combined CABG and valve
|
7.4–7.9[3]
[4]
|
|
Isolated AVR
|
1.5–4.8[12]
[109]
[110]
|
|
Isolated MVR
|
1.4–8.8[3]
[110]
|
|
Multiple valve surgery
|
9.7[3]
|
|
Aortic repair
|
4.7–7.2[111]
[112]
|
|
Percutaneous
|
PCI
|
0.18–0.5[1]
[2]
[5]
|
|
TAVI
|
2.7[12]
|
Abbreviations: AVR, aortic valve replacement; CABG, coronary artery bypass graft;
MVR, mitral valve repair; PCI, percutaneous coronary intervention; TAVI, transcatheter
aortic valve implantation.
Technical aspects of the individual procedures may account for some of the differences
in perioperative stroke risk. Among the myriad techniques in cardiac procedures, one
of the most extensively studied is off-pump CABG (OPCABG), in which coronary anastomosis
is achieved without the use of cardiopulmonary bypass. One meta-analysis of 40 randomized
trials found a pooled in-hospital stroke incidence of 1.34% in the OPCABG group compared
with 2.00% in the CABG group (odds ratio [OR], 0.72; 95% confidence interval [CI],
0.56–0.92; p = 0.009; I
2 = 0%).[7] However, none of the three largest randomized controlled trials evaluating OPCABG,
each with over 2,000 subjects, found a significant reduction in the rate of in-hospital
stroke. It remains controversial whether this technique in fact decreases the risk
of perioperative stroke compared with conventional CABG.[8]
Cardiac catheterization also carries a different risk of stroke depending on whether
or not an intervention is performed. For example, one large single-center retrospective
study examining the rate of periprocedural stroke found an incidence of 0.09% for
purely diagnostic cardiac catheterizations, versus 0.23% for which an intervention
such as PCI is performed.[9]
Another procedure that deserves further discussion is TAVI, now well accepted as a
less invasive alternative to surgical aortic valve replacement (AVR). Two early landmark
trials using the same first-generation device found a 30-day incidence of stroke of
6.7% in patients who were not surgical candidates, and 4.6% in high-risk patients
who were otherwise surgical candidates (compared with 2.4% in the surgical arm, p = 0.07).[10]
[11] However, subsequent trials reported substantially lower 30-day incidences of stroke,
possibly attributable to improvements in device and technique, inclusion of lower
risk individuals, as well as more rigorous adjudication methodology. A recent meta-analysis
of 22 propensity score–matched observational studies and 6 randomized controlled trials
found a 30-day rate of stroke of 2.7 and 3.1% in the TAVI and surgical AVR groups,
respectively, without statistically significant difference.[12] In recent years, cerebral embolic protection devices have emerged as a promising
means to decrease the burden of both clinical and subclinical embolic infarcts resulting
from TAVI. However, the clinical efficacy of these devices remains to be proven in
large randomized controlled studies.[13]
Lastly, it is important to note that the aforementioned incidence data are largely
based on a clinical definition of stroke, consisting of a focal neurological deficit
persisting for more than 24 hours, with or without adjudication by a neurologist.
The periprocedural rate of clinically “silent” infarcts detectable on MRI is in fact
many times higher than symptomatic strokes. A 2017 meta-analysis of studies in which
early postprocedural MRI was performed found a staggering rate of radiographic infarcts
in 27% of patients undergoing CABG and 80% of those undergoing TAVI. In the same study,
the rate of radiographic infarcts was 10 times that of the combined rate of clinical
strokes and transient ischemic attacks (TIAs).[14] The cognitive consequences of silent brain infarcts will be discussed later in this
article.
Timing and Mechanism
In patients who undergo CABG, less than half of perioperative strokes are identified
upon awakening from anesthesia, that is, presumed to have occurred intraoperatively,
whereas the remaining 55 to 63% of patients are diagnosed from the first postoperative
day onward. Most strokes are apparent within the first week.[6]
[15]
[16] A similar temporal pattern of onset has been observed with TAVI,[17] while corresponding data for PCI are lacking and conflicting.[9]
[18]
The large majority of strokes after cardiac procedures are ischemic as opposed to
hemorrhagic. Proximal embolization from the heart or aortic arch is the most common
etiology in both the intraoperative and postoperative periods. By contrast, hypoperfusion
is a less common cause of stroke than most readers might expect. In a retrospective
study examining etiology of 388 cases of stroke related to isolated CABG, 62.1% were
determined to be embolic, and only 8.8% were deemed to be due to hypoperfusion.[15] In the intraoperative period, embolism occurs due to release of particulate matter
from manipulation of the aortic arch and heart as well as from the cardiopulmonary
bypass pump. In the postoperative period, embolism occurs in the setting of increased
thrombosis, including postoperative atrial fibrillation (POAF) and a general hypercoagulable
state.[15]
[19] Surgical trauma, general anesthesia, immobility, and perioperative holding of baseline
antithrombotic medications all contribute to thromboembolism. Aortic plaques that
were disturbed during the procedure may also cause delayed thromboembolism. However,
not all periprocedural emboli are thrombotic in nature. In one study examining debris
captured by an embolic protection device during TAVI, both thrombotic (73%) and tissue-derived
(63%) debris were found with high prevalence.[20] Uncommonly, a calcified embolus may be detected on noncontrast CT brain ([Fig. 1]).[21]
Fig. 1 A 59-year-old woman presented with aphasia 6 hours following a transcatheter aortic
valve implantation procedure. Noncontrast CT head revealed a focal hyperdensity in
the left Sylvian fissure consistent with a calcified embolus (arrow).
In addition to cerebral infarction, this embolization of atherosclerotic plaque material
can cause multisystem organ dysfunction, termed “cholesterol embolization syndrome.”
This can occur after either endovascular or open cardiac procedures, and is composed
of organ-specific dysfunction and constitutional symptoms. Cerebral cholesterol embolization,
particularly of a smaller shower of emboli, can lead to global neurologic dysfunction
characterized by confusion or memory impairment rather than focal neurologic deficits.[22] Unlike thromboemboli, cholesterol emboli can lead to progressive or new dysfunction
postprocedurally; the inflammatory reaction surrounding nonocclusive cholesterol emboli
can lead to intraluminal thrombus formation over the 24 to 48 hours following embolization.
Infarction can also occur in an even more delayed fashion, as the late stages of the
local inflammatory response lead to endothelial proliferation and intimal fibrosis,
potentially causing delayed vascular stenosis or occlusion.[22] Definitive diagnosis can only be made with biopsy of an affected tissue, but the
concomitant presence of other organ-specific dysfunction can clue one in to the possibility
that intracranial emboli may be cholesterol emboli. The most commonly affected organs
are kidneys, skin, and the gastrointestinal tract.[22]
[23] Careful examination may also reveal retinal Hollenhorst plaques.[22]
[23] In the appropriate clinical setting, a pathologic diagnosis can be deferred and
the diagnosis can be made clinically.
Although carotid artery stenosis has been consistently shown to be a risk factor for
perioperative stroke, especially in the setting of CABG, there is controversy in the
literature regarding its importance as a direct causal factor.[24] One systematic review of small case series estimated that up to 67% of strokes after
CABG cannot be attributed to carotid disease alone based on location (contralateral,
bilateral, or posterior circulation involvement).[25] Carotid artery stenosis can directly cause strokes via two potential mechanisms:
hypoperfusion due to flow restriction and plaque rupture resulting in artery-to-artery
embolism. Hypoperfusion-related strokes can usually be distinguished from embolic
strokes based on a temporal correlation with hypotension, the presence of an ipsilateral
high-grade vascular stenosis, as well as a characteristic pattern of distribution
on imaging ([Figs. 2] and [3]). However, emboli may also preferentially travel to watershed zones.
Fig. 2 An 82-year-old woman developed acute confusion 36 hours post–coronary artery bypass
graft. Magnetic resonance imaging revealed punctate foci of diffusion restriction
in multiple vascular territories consistent with proximal embolic “shower.” Note that
although clearly embolic, some of the infarcts occur in the deep watershed zone.
Fig. 3 A 73-year-old man reported mild left arm weakness and numbness immediately after
percutaneous coronary intervention for a non-ST elevation myocardial infarction. He
had known bilateral internal carotid artery stenosis, graded as >70% on the right
and 50 to 69% on the left by ultrasound criteria. Note the classic “string of pearls”
pattern of infarcts in the bilateral deep watershed zones seen on diffusion-weighted
sequence (left). Also note that only some of the lesions demonstrate hypointensity
on apparent diffusion coefficient sequence (right, arrow), indicating that not all
are acute.
Hemorrhagic strokes, which include primary intracerebral hemorrhage and subarachnoid
hemorrhage, are very rare in the setting of cardiac procedures.[9]
[15]
[26]
[27]
[28] Presumably these may be triggered by the use of high-dose antithrombotic medications
in the periprocedural period in patients who are already at risk of spontaneous hemorrhagic
stroke, such as those with cerebral small vessel disease, cerebral amyloid angiopathy,
or unruptured aneurysms. Clinicians must be careful to avoid misdiagnosing an ischemic
stroke with hemorrhagic transformation as a primary intracerebral hemorrhage. Other
uncommon etiologies of stroke are listed in [Table 2].
Table 2
Uncommon causes of strokes following cardiac procedures
|
Air embolism from cardiopulmonary bypass and vascular access
|
|
Paradoxical embolism from deep vein thrombosis in patients with patent foramen ovale
or atrial septal defect
|
|
Extracranial cervical artery dissection resulting from hyperextension of the neck
during induction of anesthesia
|
|
Iatrogenic aortic dissection with extension into the common carotid arteries
|
|
Hemorrhagic stroke resulting from intraoperative heparin bolus
|
Risk Factors
Risk factors for stroke following cardiac procedures are listed in [Table 3]. Increased awareness of these risk factors can aid prevention strategies to minimize
perioperative stroke risk. The most consistently reported risk factors for periprocedural
stroke after cardiac procedures include female sex, previous stroke or TIA, atrial
fibrillation (AF; preexisting and new onset), systolic dysfunction, and chronic renal
disease. Because prior history of an ischemic cerebrovascular event is one of the
strongest and most consistent predictors of periprocedural stroke, patients who have
had a recent stroke or TIA should delay having any nonurgent cardiac procedures until
their stroke workup and secondary prevention have been optimized.
Table 3
Risk factors for strokes following cardiac procedures[a]
|
Risk factors common to all procedures[b]
|
Older age
Female sex
Previous stroke or TIA
Systolic dysfunction
Renal disease
Underweight or low body surface area
Left main stem coronary disease
Emergency presentation with acute coronary syndrome (nonelective case)
Carotid stenosis
Chronic obstructive pulmonary disease
Blood transfusion[113]
POAF
|
|
Risk factors specific to CABG[2]
[3]
[4]
[6]
[19]
[28]
[32]
[33]
[114]
|
Non-white race
Preoperative atrial fibrillation
Peripheral vascular disease
Diabetes
Hypertension
Atherosclerosis of the ascending aorta
On-pump CABG
Hypothermic circulatory arrest
Prolonged cardiopulmonary bypass and aortic cross-clamp time
Previous cardiac surgery
Preoperative infection
Combined procedures
Postoperative thrombocytopenia
|
|
Risk factors specific to PCI[5]
[9]
[26]
[27]
[115]
[116]
|
PCI of an existing bypass graft Hemodynamic instability
Intra-aortic balloon pump placement
Triple vessel disease
Presence of coronary arterial thrombus
Valvular disease
|
|
Risk factors specific to TAVI[17]
[117]
[118]
|
More severe baseline aortic regurgitation
Multiple device implantation attempts
Dislodgement of TAVI prosthesis
|
Abbreviations: CABG, coronary artery bypass graft; MVR, mitral valve repair; PCI,
percutaneous coronary intervention; POAF, postoperative atrial fibrillation; TAVI,
transcatheter aortic valve implantation; TIA, transient ischemic attack.
a The most consistently reported risk factors are in bold.
b References are listed separately below for each procedure.
The procedural approach also influences risk of stroke. For example, on-pump CABG
is associated with a higher risk of perioperative stroke than OPCABG (beating heart
CABG), though the latter is usually reserved for selected higher risk patients, due
to higher technical difficulty.[7]
[29]
[30]
[31] Predictive models for stroke risk following CABG based on readily available clinical
variables have been proposed and validated.[32]
[33]
Risk Factors: Carotid Stenosis
The neurologist may be asked to assess patients with known high-grade (50–99%) carotid
stenosis in preparation for cardiac surgery. In these instances, it is vital to distinguish
on history whether the carotid stenosis is symptomatic, which is generally defined
as a history of TIA or stroke in the vascular territory of the stenotic carotid artery.
Recent symptoms confer a much higher risk than remote symptoms, and many authors use
a cut-off of 6 months as the window beyond which carotid artery stenosis is no longer
considered “symptomatic,”[34]
[35] though this is somewhat arbitrary. One of the few CABG outcome studies that distinguished
between symptomatic and asymptomatic carotid disease found a perioperative stroke
risk of 18 and 26% in unilateral and bilateral symptomatic disease, respectively.[25]
Asymptomatic high-grade carotid stenosis, while also a risk factor for perioperative
stroke, may be considered an epiphenomenon for overall atherosclerotic burden rather
than a significant mechanism of periprocedural stroke. There is no evidence to support
routine prophylactic revascularization of unilateral asymptomatic carotid stenosis
prior to CABG.
An additional category of carotid disease that must be considered separately is chronic
carotid occlusion. While these patients have an even higher risk of perioperative
stroke than those with 50 to 99% stenosis,[25] revascularization is not advocated in chronic complete occlusion, and efforts should
be directed toward other means to optimize surgical risk.
Accordingly, both American and European guidelines recommend that preoperative carotid
revascularization be considered in only three instances: symptomatic high-grade stenosis,
asymptomatic bilateral high-grade stenosis, or asymptomatic high-grade stenosis with
contralateral carotid occlusion.[35]
[36] Guidelines recommend against revascularization of asymptomatic unilateral carotid
stenosis or stenosis <50%. Furthermore, as there is no evidence that routine preoperative
screening for carotid stenosis reduces the risk of perioperative stroke,[24] screening carotid duplex ultrasound should be limited to patients with a recent
TIA or stroke, and those with high-risk features such as age >65 and known peripheral
vascular disease.[35]
[36]
In patients with concurrent high-grade carotid disease and coronary artery disease
requiring revascularization, PCI would generally be favored over CABG due to its lower
risk of periprocedural stroke, though other factors may make CABG the only feasible
option. Carotid revascularization can be accomplished by either carotid endarterectomy
(CEA) or carotid artery stenting (CAS), with equally robust evidence in isolated symptomatic
carotid stenosis.[37] No prospective studies have compared these two procedures in patients undergoing
planned cardiac procedures such as CABG. The timing of carotid revascularization and
CABG may be simultaneous, staged (carotid before CABG), or reverse staged (carotid
after CABG). Meta-analyses of observational comparisons of staged versus simultaneous
CEA or CAS with CABG do not clearly favor either timing strategy, and it should be
noted that these studies included predominantly asymptomatic carotid stenosis and
may be affected by inherent selection bias.[38]
[39]
[40]
[41] One consideration is that following CAS, most clinicians will recommend at least
30 days of uninterrupted dual-antiplatelet therapy to prevent in-stent thrombosis.
Therefore, the decision to consider CAS versus CEA before CABG requires multidisciplinary
discussion. In cases where revascularization is not performed, whether due to patient-specific
factors in individuals with carotid stenosis or to lesions in other locations such
as intracranial arterial stenoses, it is reasonable to take precautions including
avoidance of significant hypotension intraoperatively, such as by setting a threshold
MAP >70 mm Hg.
Risk Factors: Atrial Fibrillation
Atrial fibrillation is encountered in the periprocedural period as either preexisting
or new onset following the procedure, and the distinction is important for etiological
attribution and management considerations.
In patients undergoing CABG, preexisting AF increases the risk of perioperative stroke.[2]
[4] The type of procedure and individual thromboembolic risk must be accounted for in
periprocedural antithrombotic planning. It is necessary to hold oral anticoagulation
for at least several days preoperatively prior to open cardiac surgeries. Major guidelines
recommend holding warfarin 5 days before major surgery with high bleeding risk, including
cardiac surgeries.[42]
[43]
[44] Bridging with low-molecular-weight heparin or unfractionated heparin should be considered
for those with high thromboembolic risk, for example, those with CHADS2 score of 5 or 6.[42]
[43] For patients on direct oral anticoagulants with normal renal function, it is recommended
to hold for 48 hours before a major surgery.[42]
[43] This duration would need to be longer in patients with reduced renal function, depending
on the pharmacokinetics of each specific agent. Bridging is not indicated for direct
oral anticoagulants. Although no precise recommendations are made in major guidelines
regarding continuation of anticoagulation for percutaneous procedures, retrospective
evidence suggests that continuous oral anticoagulant use is relatively safe in PCI
and AF ablation.[44]
[45]
[46]
New-onset POAF is an important cause of perioperative stroke. It is a morbid condition
independently associated with perioperative stroke in most, but not all, studies of
CABG[19]
[32]
[47]
[48]
[49]
[50]
[51] and in both PCI and TAVI.[35]
[52] Furthermore, POAF has adverse hemodynamic effects, is associated with higher in-hospital
mortality and increased duration of hospitalization, and is a predictor of stroke
occurring in the years after CABG.[49]
[53]
[54]
[55] POAF occurs due to multiple factors including electrolyte imbalance, catecholamine
release, atrial ischemia, and pericardial inflammation.[56] Predictors of new-onset POAF are listed in [Table 4]. The rate of POAF is as high as 65% after combined CABG and valve surgery.[57]
[58] Incidence is moderate after isolated CABG, ranging from 18.0 to 29.5%,[53]
[57] lower after TAVI (6–11%),[35]
[52] and quite low (0.1–6%) after PCI.[35]
[52]
[53] New-onset AF can also occur as a complication of patent foramen ovale closure for
secondary stroke prevention, with an incidence of 0.4 to 5.0%.[59]
[60]
[61]
[62] Current guidelines recommend the use of β-blockers as first-line primary prophylaxis
for the development of POAF in patients undergoing CABG.[35] While studies have demonstrated the efficacy of β-blockers and antiarrhythmics in
the prevention of POAF, a decreased risk of perioperative stroke has not been proven.[63]
Table 4
Predictors of new-onset postoperative atrial fibrillation
|
Increasing age
|
|
Male sex
|
|
Obesity
|
|
Preoperative heart failure
|
|
Combined CABG and valve surgery
|
|
Perioperative β-blockade
|
|
Higher positive fluid balance on postoperative days 0–2
|
|
Increased white blood cell count postoperatively
|
|
Increased serum creatinine postoperatively
|
|
Low serum phosphate postoperatively
|
|
Higher serum magnesium postoperatively
|
|
Higher serum C-reactive protein postoperatively
|
Abbreviation: CABG, coronary artery bypass graft.
Left atrial appendage ligation (LAAL) is frequently performed during cardiac surgical
procedures in patients with preexisting AF, with the goal of long-term stroke prevention.
A meta-analysis of mostly observational studies consisting of more than 280,000 patients
showed significant reductions in both perioperative and long-term stroke risk, with
a relative risk of 0.66 and 0.67, respectively.[64] However, two large retrospective cohort studies suggest that this intervention may
increase the risk of POAF, though they did not demonstrate an increased risk of perioperative
stroke.[65]
[66] A large randomized controlled trial is underway and is expected to complete follow-up
in 2022.[67]
Monitoring
There are multiple methods of monitoring for hypoperfusion or emboli during cardiac
surgery, including near-infrared spectroscopy (NIRS), electroencephalography (EEG),
and transcranial Doppler ultrasonography (TCD). Although these intraoperative monitoring
techniques have some supportive evidence, they have not achieved widespread usage.
NIRS uses light emitted from a probe to evaluate the mixed (arterial and venous vessels
<1 mm in diameter) vascular oxygen saturation by taking advantage of differing absorption
spectra of oxyhemoglobin and deoxyhemoglobin. A systematic review of randomized controlled
trials by Serraino and Murphy showed that the use of a NIRS-based protocol did not
have any effect on the risk of stroke in cardiac surgery patients, with a relative
risk of 1.08 (95% CI: 0.40–2.91).[68]
EEG can also be used during cardiac surgery, and while EEG changes may be somewhat
specific for acute brain injury in the setting of normal baseline EEG and stable anesthesia,
EEG requires live expert interpretation to be clinically useful to detect intraoperative
stroke and is not sensitive.[69]
TCD can be used to either monitor cerebral blood flow or for the detection of microembolic
signals. TCD detects cerebral microemboli as high-intensity transient signals (HITS).
These microemboli indicate higher risk of concomitant macroemboli which may cause
clinical stroke. The embolic risk related to TAVI has been confirmed by TCD in a study
by Kahlert et al, wherein intraprocedural HITS were observed in 100% of 83 patients
undergoing TAVI, and these primarily occurred during manipulation of the calcified
aortic valve.[70] HITS should be interpreted with some caution, however, as they may be caused by
air microbubbles rather than microemboli. This is particularly notable during PCI.
Bladin et al showed that 70% of HITS during PCI occurred during injection of saline
or contrast,[71] rather than during maneuvers (such as catheter manipulation), which would be expected
to cause embolic phenomena.
Postoperatively, monitoring should include continuous cardiac telemetry, particularly
after CABG and open valve replacements, after which the risk of POAF is highest. Routine
neurologic assessments should also be performed by nursing staff to monitor for development
of neurologic deficits.
Hyperacute Stroke Management
If there is a concern for new neurologic deficit potentially representing a stroke
after a cardiac procedure, hospital-specific acute stroke protocols should be activated.
These should include neurological examination including the National Institutes of
Health Stroke Scale,[72] confirmation of the time the patient was last known well, blood pressure and blood
glucose measurements, and rapid performance of brain and cerebrovascular imaging.
In centers without rapid access to stroke-trained personnel, the use of a teleneurology/telestroke
system can facilitate rapid evaluation. In most centers, hyperacute imaging is best
performed with noncontrast head computed tomography and computed tomographic angiography
of the head and neck. In select centers, hyperacute magnetic resonance imaging (MRI)
of the brain and magnetic resonance angiography of the head and neck are performed.
MRI is generally not possible in the first few days after open cardiac surgeries,
during which non–MRI-compatible pacing wires are frequently present.
Treatment options for suspected hyperacute stroke include thrombolysis and thrombectomy.
The AHA/ASA 2018 guidelines for the early management of acute ischemic stroke state
that intravenous “alteplase is reasonable for the treatment of AIS [acute ischemic
stroke] complications of cardiac or cerebral angiographic procedures, depending on
the usual eligibility criteria.”[73] Recent major surgery and coagulopathy are contraindications to intravenous thrombolysis,
and most vascular neurologists would consider the risk of surgical site hemorrhage
to outweigh potential benefit in the postoperative period after sternotomy. However,
after percutaneous procedures, the risk of surgical site bleeding is lower, and intravenous
thrombolysis can be considered.[74] The safety of thrombolysis in patients who present with strokes after cardiac catheterization
was examined in a 2008 multicenter retrospective cohort study, in which outcomes in
the 12 treated patients (7 intravenous and 5 intra-arterial) compared favorably with
the 54 untreated patients.[75] It is important to keep in mind that heparinoids are frequently administered during
cardiac catheterization, and after heparin administration intravenous thrombolysis
should be given only if the prothrombin time has normalized. Although none of the
three patients in the aforementioned cohort who were treated despite prothrombin times
over 40 seconds developed a hemorrhagic complication, the AHA/ASA guidelines recommend
against the use of intravenous alteplase in patients with prolonged prothrombin times.[73]
[75]
Mechanical thrombectomy has been performed in stroke after cardiac surgery[73] as well as catheter-based procedures,[76] and can be considered within 24 hours of postoperative stroke onset on a case-by-case
basis. Thrombectomy should be considered in patients with occlusions of the intracranial
carotid artery, middle cerebral artery M1 segment, and in some cases and centers proximal
occlusions of the M2 branches of the middle cerebral artery. In selected cases, mechanical
thrombectomy may be performed for occlusions of the basilar or posterior cerebral
arteries. Patients with a large vessel occlusion who are not currently at a thrombectomy-capable
center should be transferred immediately to a thrombectomy-capable center. Thrombectomy
can be performed in patients with a large vessel occlusion without additional imaging
beyond a noncontrast CT (to rule out hemorrhage) if it is within 6 hours of the time
last known well. Patients who were last known well 6 to 24 hours before thrombectomy
should undergo additional specialized imaging with CT or MR perfusion imaging, and
thrombectomy performed if the patients meet the DAWN (6–24 hours)[77] or DEFUSE-3 (6–16 hours)[78] eligibility criteria. The DAWN criteria require a clinical-imaging mismatch with
varying cut-offs for maximum core infarct volume based on age and clinical stroke
severity. The DEFUSE-3 criteria require core infarct volume <70 mL, ratio of ischemic
tissue to core infarct of ≥ 1.8, and penumbra of larger than 15 mL.
Secondary Prevention
For patients with perioperative stroke and no indication for anticoagulation, antiplatelet
therapy is the mainstay of treatment. As long as at least a single antiplatelet agent
is administered, it is reasonable to defer the choice of antiplatelet therapy to cardiology/cardiac
surgical teams, though risk of hemorrhagic conversion should be weighed against thrombotic
risk, particularly if dual-antiplatelet therapy is being considered.
For patients with perioperative stroke and an indication for anticoagulation, the
timing of resumption of anticoagulation must be weighed carefully. Risk of recurrent
stroke must be balanced against the risk of surgical bleeding and risk of hemorrhagic
conversion of the stroke. American and European guidelines recommend restarting anticoagulation
for AF within 14 days of stroke,[73]
[79] but the timing of resumption within that 14-day range is unclear. The American Heart
Association/American Stroke Association 2018 guideline recommends starting oral anticoagulation
between 4 and 14 days after stroke.[73] The European Heart Rhythm Association provides more concrete guidance based on clinical
stroke severity via the National Institutes of Health Stroke Scale score, with recommended
oral anticoagulant resumption timelines varying from 1 to 12 days after stroke.[79] These guideline recommendations are based on observational data and expert opinion;
as to date, there have not been large randomized controlled trials addressing this
issue. Regardless of the timing of initiation of anticoagulation, for patients with
strokes at higher risk of hemorrhagic conversion, it is often prudent to initially
use intravenous anticoagulant infusions such as unfractionated heparin rather than
oral anticoagulation given the ability to quickly reverse the agent if hemorrhage
does occur. If the patient demonstrates clinical and/or imaging stability on intravenous
anticoagulation, and with increased time since infarction, clinicians can then consider
transitioning to the oral anticoagulant of choice.
Whether or not patients with preoperative AF who undergo LAAL should resume anticoagulation
is currently unknown. Exclusion of the left atrial appendage is not always complete,
with success rate for occlusion (by postoperative transesophageal echocardiography)
ranging from 66 to 95%.[80]
[81]
[82]
Historically, new-onset POAF was considered a short-term complication that did not
result in serious morbidity or mortality.[83] While POAF onset peaks on postoperative days 2 to 3 with a median duration of 22 hours,[53]
[57] and indeed often is (at least initially) transient with only 2.8% of POAF patients
having persistent AF on discharge,[57] it is associated with significant long-term consequences.
Butt et al showed in a cohort of patients with left-sided valvular surgery that POAF
patients were similarly likely to be initially treated with oral anticoagulants compared
with new-onset nonvalvular atrial fibrillation (NVAF) patients, but POAF patients
were less likely to still be taking oral anticoagulants at 1 year compared with NVAF
patients.[84] Though they were less likely to be on oral anticoagulants at 1 year, patients with
POAF had similar risk of thromboembolism as NVAF (HR: 1.22; 95% CI: 0.88–1.68). This
similar thromboembolic risk is not mediated by recurrent AF, as POAF patients after
all types of cardiac surgery had lower risk of recurrent AF compared with NVAF (HR:
0.62; 95% CI: 0.56–0.70), but the subset of patients who underwent mitral valve surgery
had similar risk of recurrent AF when compared with NVAF patients.[84] While this discrepancy between rates of recurrent AF and thromboembolism may represent
subclinical short AF events, it is not clear why subclinical events would not be equally
prevalent in both groups. It is therefore possible that POAF indicates the presence
of an atrial cardiopathy that itself increases thromboembolic risk.[85]
[86]
[87]
[88]
[89]
[90]
Multiple major international guidelines have addressed the question of antithrombotic
management of POAF. The American Heart Association/American College of Cardiology/Heart
Rhythm Society guidelines state it is reasonable to consider antithrombotic therapy
for POAF patients just as would be done for patients with AF of other etiologies.[91] The European Heart Rhythm Association's guidelines recommend consideration of antithrombotic
therapy if the duration of POAF is at least 48 hours.[92] The Canadian Cardiovascular Society recommends consideration of anticoagulation
if POAF lasts at least 72 hours and is present at hospital discharge, and recommends
reexamination of the anticoagulation decision at 6 to 12 weeks postoperatively.[93]
Cognitive Complications
Cardiac surgeries result in both acute and chronic cognitive complications. Both early
and late cognitive complications are more common after open cardiac surgeries, though
they can occur in catheter-based procedures as well. Early postoperative cognitive
dysfunction is likely caused by contributions from embolism, hypoperfusion injury,
blood–brain barrier injury from systemic inflammation, as well as toxic–metabolic
encephalopathy and ICU delirium. The presence of late cognitive decline implies that
some permanent cerebral injury occurs in the perioperative period.
The argument for cerebral hypoperfusion as a contributing factor in early perioperative
cognitive dysfunction is supported by a study of 92 patients by Siepe et al.[94] This study showed that increased systemic perfusion pressure (mean arterial pressure
of 80–90 compared with 60–70) during cardiopulmonary bypass was associated with reduced
risk of postoperative delirium. This association was present despite a lack of difference
between groups in intraoperative cerebral oxygenation as measured by NIRS. Another
putative causative factor, systemic inflammation, has been demonstrated postoperatively,[58]
[95] but there are currently no treatments that have consistently shown benefit on this
mechanism.
There is some limited evidence for modulating sympathetic activity in preventing acute
cognitive dysfunction after cardiac surgery; perioperative dexmedetomidine was shown
to be beneficial in reducing postoperative delirium (adjusted OR: 0.350; 95% CI, 0.212–0.578).[96]
Embolic ischemic cerebral injury is a clear contributor to both acute and chronic
neurocognitive dysfunction. Embolic-appearing diffusion-restricting brain lesions
on MRI are very common after cardiac procedures, particularly after CABG and valve
surgeries (both open and transcatheter). The incidence of new cerebral ischemic lesions
on MRI ranges from 31 to 40%[97]
[98]
[99] after open cardiac surgery, and as high as 90% after TAVI.[100] Barber et al showed cognitive dysfunction at 5 days and 6 weeks postoperatively
in 15 of 15 patients with new ischemic brain lesions (the majority of which were silent)
versus only 6 of 17 patients without new ischemic lesions (p < 0.001).[97]
While silent ischemic lesions are associated with cognitive decline, intraoperative
embolic signals detected by TCD have not been similarly correlated with early cognitive
dysfunction; however, they may play a greater role in chronic cognitive dysfunction.
Using intraoperative TCD microembolic signals, Liu et al showed that microembolic
signals were reduced from a median of 430 to 2 when comparing surgery with cardiopulmonary
bypass and off-pump surgery, but there was no difference in the incidence of postoperative
cognitive dysfunction between the two surgical techniques at either 1 week or 3 months.[101] This lack of early difference with microemboli reduction with OPCABG was corroborated
in a similar study by Stroobant et al,[102] though the off-pump group demonstrated cognitive impairment on fewer neuropsychological
tests 6 months postoperatively.
Silent cerebral microbleeds have also been identified postoperatively after cardiac
surgery. A study by Patel et al showed a 24% incidence of new cerebral microbleeds,
and there was a linear association with longer time on cardiopulmonary bypass, but
there was no association with cognitive outcomes.[99]
The time course of chronic postoperative cognitive decline raises questions about
its mechanisms. There is not only a step-off from baseline cognition after surgery,
as would be expected from pure perioperative ischemic injury, but also progressive
postsurgical decline. Newman et al performed a battery of neurocognitive tasks at
preoperative, in-hospital, 6-week, 6-month, and 5-year time points. In both patients
who were and who were not cognitively impaired at discharge, cognition improved postoperatively,
peaking at the 6-month time point, and then decreased again at the 5-year time point.
Though both groups followed this same general trajectory over time, the group without
cognitive decline prior to discharge returned to baseline cognition at 6 months, whereas
those with cognitive decline prior to discharge did not. Those with cognitive decline
prior to discharge also had a more severe drop in cognition between the 6-month and
5-year evaluations.[103] It is unclear whether this accelerated cognitive decline seen in some patients post–cardiac
surgery reflects the presence of an underlying neurodegenerative disorder, or whether
the surgery itself unmasks or accelerates cognitive decline. This determination is
confounded by the presence of vascular risk factors, which are prevalent in both patient
populations who undergo cardiac surgery and those who develop dementia. There are
currently no large studies with appropriate control arms to determine whether the
rate of progressive cognitive decline after cardiac surgery is different than would
be expected in this patient population with vascular risk factors.
Lastly, it is possible that for some patients, improved cerebral blood flow and quality
of life may in fact contribute to better cognitive function after cardiac procedures.
One prospective cohort study trended an extensive battery of cognitive tests in 51
patients undergoing TAVI and found an average improvement in the cognitive status
persisting at 1 year, though unfortunately no imaging data were available to correlate
individual cognitive trajectories with silent ischemic lesions.[104]
