Cerebral Hyperperfusion After Carotid Stenting: Who Is at Risk?

May 22, 2019

Cerebral hyperperfusion syndrome — a rare but severe complication following carotid revascularization — may occur in up to 3% of patients undergoing carotid stenting. A new prospective study suggests factors linked to an increased risk include female sex, older age, history of chronic kidney disease, and a treated left carotid artery.

The findings, from a Spanish study known as HISPANIAS (HyperperfusIon Syndrome Post-carotid ANgIoplasty And Stenting), was published in the May 13 issue of JACC: Cardiovascular Interventions.

Cerebral hyperperfusion syndrome occurs rarely as a potential complication of removing the carotid stenosis, allowing sudden excessive blood flow to the brain. Symptoms include headache, eye and face pain, vomiting, focal deficit, seizures, or decreased level of consciousness, and — as a worst case scenario — intracerebral hemorrhage (ICH).

However, the HISPANIAS authors, led by Alejandro González García, MD, PhD, Hospital Virgen del Rocío, Seville, Spain, note that knowledge of cerebral hyperperfusion syndrome among physicians is limited, and few data are available about its incidence, risk factors, and pathophysiology.

"The general aim of the study was to develop a clinical and biological predictive model for CHS after carotid artery stenting, which would enable us to reduce the appearance of this complication in the future to make endovascular treatment of this condition safer," they write.

The HISPANIAS study involved 757 coronary stenting procedures performed at 14 Spanish hospitals. All patients underwent a comprehensive neurologic examination, carotid duplex evaluation, transcranial Doppler ultrasonography before and after stenting, and brain CT or MRI before stenting. The patients who presented with symptoms of cerebral hyperperfusion syndrome also underwent CT or MRI on the same day of symptom onset.

Results showed that cerebral hyperperfusion syndrome occurred in 2.9% of patients overall, with 2.1% of patients having moderate-severe symptoms and 0.8% having mild symptoms (only headache).

The median time of onset of cerebral hyperperfusion syndrome symptoms was 6 hours. Five patients with moderate-severe symptoms had intracranial hemorrhage (31.3%).

The 30-day mortality rate in the overall study cohort was 0.8%. However, in patients who suffered cerebral hyperperfusion syndrome the mortality rate was 9.1%, increasing to 12.5% in those with moderate-severe symptoms. In comparison, patients who did not develop cerebral hyperperfusion syndrome had a mortality rate of just 0.5%.

Preoperative predictors of moderate-severe cerebral hyperperfusion syndrome were female sex (odds ratio 3.24); older patients (1.09); left carotid artery treated (4.13); and chronic renal failure (6.29).

An Overestimate?

In an accompanying editorial, Gary Roubin, MD, PhD, a cardiologist with Cardiovascular Associates of the Southeast in Birmingham, Alabama, suggests that the 2.9% incidence of cerebral hyperperfusion syndrome in the HISPANIAS study may be an overestimate.

"They took all the nonspecific symptoms that could be cerebral hyperperfusion syndrome and related them to increased blood flow," Roubin told Medscape Medical News, "But there is always going to be increased blood flow after the removal of a stenosis, and some of those symptoms could have been due to other things such as air or embolic matter. They tried to exclude these other causes but I’m not sure they methods were precise enough to do that.”

Roubin also pointed out that the ICH rate in the study (0.7%) was over twice the rate reported in previous rigorous studies of carotid stenting, and he raised some questions about some of the methodologies used in the Spanish study, in particular that 25% of the HISPANIAS patients did not have embolic protection, and also large dilatation balloons were used. "That would not happen in our practice," he noted.

He said there was little information on how the hemodynamics were managed in the study, which can have a major effect on the occurrence of cerebral hyperperfusion syndrome.

"This syndrome should be extremely rare if the hemodynamics are managed correctly during the carotid stenting process," Roubin stressed. "We would routinely embrace the natural hypotension that occurs by putting the stent in the bifurcation. There are receptors there that interpret this as increased blood pressure, so they signal to lower blood pressure, which comes down quite precipitously.

"This doesn’t cause major problems but sometimes operators can overreact to this and give hypertensive agents, which can induce cerebral hyperperfusion syndrome," he continued. "If the [blood] pressure is rising it is imperative that it is lowered quickly to protect the brain, but that should happen routinely."

Roubin, however, says the study is important as it raises awareness of cerebral hyperperfusion syndrome, which he believes is probably not discussed sufficiently, and highlights those most at risk. "We must be ultra-cautious about avoiding high pressures in patients with the risk factors identified."

He also notes that the HISPANIAS study provides more reassurance on mortality rates with carotid stenting. "It is a large prospective series of carotid-stenting patients with a very low death rate, which is similar to recent contemporary trials and should help to reduce the levels of resistance to the procedure," he commented.  

The HISPANIAS study was supported by a Spanish grant from the Instituto de Salud Carlos III. González García has disclosed no relevant financial relationships . Roubin has received royalties from Cook and holds equity in Essential Medical.

JACC: Cardiovascular Interventions. Published online May 13, 2019.  Abstract, Editorial

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