- A registry study found an 8% incidence of stroke at 1.4 years after LVAD placement, accompanied by another 8% incidence of nonstroke neurologic adverse events.
- Pre-LVAD extracorporeal membrane oxygenation (ECMO) and concomitant surgery may be modifiable targets to reduce neurologic dysfunction.
- A more complete view of neurologic dysfunction is needed to inform decision-making, researchers said.
It's not all about stroke: Various neurologic events boded poorly for survival on the contemporary magnetically levitated HeartMate 3 left ventricular assist device (LVAD) in a retrospective registry study.
Based on the U.S. INTERMACS database, there was an 8% incidence of both stroke and nonstroke neurologic adverse events (NAEs) over a median 1.4 years among nearly 12,000 people with advanced heart failure who got the contemporary magnetically levitated LVAD.
Two-year survival rates were 45% in LVAD recipients who had a stroke and 56% in peers with nonstroke neurologic events (P<0.001). Compared with no neurologic event, there was an elevated risk of death after a stroke (HR 7.3, 95% CI 6.6-8.1) or a nonstroke neurologic event, the latter associated with:
- Highest mortality risk where there is overt central nervous system (CNS) injury (HR 12.58, 95% CI 10.39-15.23)
- High risk with covert CNS injury detected by neuroimaging (HR 9.19, 95% CI 6.75-12.51)
- Lower but still elevated risk with neurologic dysfunction without CNS injury, such as encephalopathy (HR 3.69, 95% CI 3.20-4.25)
"Stroke and nonstroke NAEs are incurred by a similar proportion of patients, and both are associated with substantially reduced survival. Consequently, stroke and nonstroke NAEs should be given comparable weight with universal nomenclature when evaluating the safety of durable LVADs," concluded a group led by Omar Saeed, MD, MSc, of Montefiore Medical Center, Albert Einstein College of Medicine in New York City, reporting in JACC: Heart Failure.
In their study, there were two potentially modifiable targets to reduce neurologic dysfunction from LVAD therapy: pre-LVAD extracorporeal membrane oxygenation (ECMO) and concomitant surgery.
A Long List of Neglected Neurologic Complications?
Much attention has centered strokes as the neurologic complication of concern in LVAD recipients. Prior work established that strokes may arise due to thromboembolism from various sources, while preexisting cerebrovascular disease, uncontrolled hypertension, and anticoagulation therapy may also contribute to stroke burden, Saeed and colleagues noted.
Other clinically significant neurologic complications, such as encephalopathy, have consequently been less well described.
"Neurological assessment after LVAD implantation should extend beyond focal stroke symptoms," commented Sung-Min Cho, DO, MHS, of Johns Hopkins University School of Medicine in Baltimore, who was not involved with the study.
Of note, Cho told MedPage Today, it may not be the case that encephalopathy itself causes death, as it may reflect underlying infection, shock, or multiorgan dysfunction. "Altered mental status/encephalopathy may warrant clinicians' attention both to possible brain injury and to the systemic illness that may be causing it, both of which increase the risk of death."
There is also an issue with attributing deaths to covert brain injury, as scans are ordered usually when a patient is already doing poorly, according to Mandeep Mehra, MD, MSc, of Brigham and Women's Hospital and Harvard Medical School in Boston, who was also not involved with the study.
Cho and Mehra both stressed the clinical heterogeneity of the so-called "nonstroke" endpoint in the study, which included overt CNS injury from subarachnoid hemorrhage (SAH), hypoxic-ischemic injury, subdural hemorrhage (SDH), or traumatic brain injury; covert CNS injury detected by neuroimaging; and neurologic dysfunction without CNS injury including encephalopathy, delirium, seizures, and transient ischemic attacks (TIA).
"SAH is a cerebrovascular event ordinarily considered a hemorrhagic stroke; SDH is generally classified separately, but grouping both under 'nonstroke neurological dysfunction' obscures the distinction between structural brain injury and conditions such as delirium in my opinion," Cho said.
"The nonstroke category needs dissecting before we give it equal weight with stroke. Seventy percent of these events are encephalopathy, delirium, seizures, or TIA. None of them were adjudicated, and in a very sick postoperative patient they are often a consequence of sepsis or multiorgan failure rather than a device-related brain injury," warned Mehra. "What we need is rigorous, adjudicated, device-attributable neurological endpoints. Lumping heterogeneous, unadjudicated events into a safety endpoint for future device trials could obscure rather than clarify device performance."
Can Neurologic Events Be Prevented?
Saeed's group performed a retrospective cohort study using the nationwide Society of Thoracic Surgeons INTERMACS database. Included were 11,739 patients who got a HeartMate 3 LVAD from 2017 to 2023.
The authors reported that pre-LVAD ECMO was associated with more stroke (HR 1.70, 95% CI 1.35-2.16) and nonstroke events (HR 1.45, 95% CI 1.11-1.90); concomitant surgery was also tied to stroke (HR 1.23, 95% CI 1.08-1.41) and nonstroke events alike (HR 1.17, 95% CI 1.03-1.34).
"Patients coming to implant on ECMO or temporary support, or undergoing concomitant procedures, carry higher neurological risk. That calls for careful thrombus screening, attention to stasis, and early neurological assessment after surgery," Mehra said.
Cho and Mehra both cautioned against calling ECMO a "modifiable" risk factor based on these findings, however. "Patients are on ECMO because they are in shock. ECMO marks severity of illness more than it represents a choice we can simply avoid," Mehra said.
It also remains to be shown that "avoiding ECMO would reduce neurological injury," according to Cho.
In any case, there is already some improvement on the neurologic safety of LVADs, as Saeed and colleagues reported that stroke and nonstroke NAEs occurred at an incidence of 0.044 and 0.049 events per patient-year, respectively, in this real-world cohort. In contrast, in the MOMENTUM3 trial, the incidence of any stroke was 0.050 events per patient-year across HeartMate 3 and HeartMate II LVAD recipients, while other neurologic events were logged at 0.073 events per patient-year.
The contemporary HeartMate 3 is already an improvement over its predecessor HeartMate II in terms of staving off neurologic complications. In a prespecified analysis of MOMENTUM 3, stroke rates were 10.1% and 19.2% in the first 2 years between the two LVAD groups, respectively (P=0.02).
"I was not at all surprised by this analysis which is itself reassuring," and "confirms that neurological complications have fallen substantially in the magnetically levitated era," said Mehra. "The device itself is no longer the dominant driver of neurological risk; the surgery and peri-implant factors are the issue."
The report found that the independent predictors of death after stroke were older age, pre-LVAD implantable cardioverter-defibrillator, higher pre-LVAD blood urea nitrogen level, and pre-LVAD dialysis. Predictors of death after nonstroke NAE were higher pre-LVAD body mass index, higher pre-LVAD serum creatinine, greater pre-LVAD international normalized ratio, and lower pre-LVAD albumin.
"Awareness of these patient-level characteristics may help direct resources to those who are most vulnerable after the occurrence of NAEs," the study authors suggested.
Saeed and colleagues nevertheless acknowledged that their retrospective study left room for bias and did not account for variables such as blood pressure management, anticoagulation management, or atrial fibrillation. Additionally, NAE events may be underestimated due to the lack of reporting of recurrent events and the classification of patients experiencing both stroke and nonstroke NAEs as stroke only.
Disclosures
This study was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute.
Saeed disclosed no conflicts of interest.
Study co-authors reported ties to Abiomed, Johnson & Johnson, Abbott, and other entities.
Mehra reported consulting fees paid to his institution from Abbott and Cadrenal and personal fees from Moderna, Natera, Transmedics, Second Heart Assist, Paragonix, NuPulseCV, FineHeart, FIRE-1, Leviticus, Seismic, and Regeneron.
Cho had no disclosures.
Primary Source
JACC: Heart Failure
