Study Focuses on Systemic Inflammation After TAVR

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Systemic inflammation occurs in a substantial proportion of patients after transcatheter aortic valve replacement (TAVR), according to a paper published online January 26, 2012, ahead of print in the European Heart Journal. Initial signs appear within hours of treatment, but the resulting mortality risk remains elevated out to 1 year.

Georg Nickenig, MD, of Rheinische Friedrich-Wilhelms-Universität Bonn (Bonn, Germany), and colleagues examined outcomes of 152 high-risk patients with symptomatic severe aortic stenosis who underwent TAVR at their center from January 2008 to June 2011. Mean patient age was 80.5 ± 6.5 years, and mean logistic EuroSCORE was 30.4 ± 8.1%. The researchers defined systemic inflammatory response as meeting 2 or more of the following criteria within 48 hours of treatment:

• Body temperature < 36.0 degrees or > 38.0 degrees Celsius
• Heart rate > 90 beats/min
• Respiratory rate > 20 breaths/min
• PaCO₂ < 32 mmHg
• Leucocyte count > 12 x 10⁹/L or < 4 x 10⁹/L

In all, 40.1% of patients developed the syndrome. Most baseline characteristics prior to treatment were similar between patients with and without inflammation; an exception was higher Society of Thoracic Surgeons mortality score in affected patients (11.4 ± 8.4% vs. 8.8 ± 6.3%; P = 0.030).

Leucocyte elevations were observed as early as 4 hours after TAVR and peaked at 48 hours. Differences in the levels of lactate and the proinflammatory cytokines IL-6 and IL-8 also were apparent at 4 hours, while procalcitonin and C-reactive protein (CRP) levels subsequently increased for affected patients at 24 hours.

Yet the consequences of inflammation did not appear transient. Mortality was increased for patients with inflammation at 30 days (18.0% vs. 1.1%; P < 0.001) and at 1 year (52.5% vs. 9.9%; P < 0.001). Survival differences remained even after excluding those who experienced periprocedural complications that might have led to death. After adjustment for the 3 strongest univariate predictors of mortality—pulmonary hypertension, acute kidney injury (AKI), and moderate/severe aortic regurgitation—systemic inflammation after TAVR continued to raise mortality risk (HR 4.0; 95% CI 1.8-9.2; P = 0.001).

In terms of potential contributing factors, patients who went on to develop systemic inflammation differed with regard to a number of periprocedural outcomes (table 1).

Table 1. Factors Associated with Systemic Inflammatory Response

Multivariate logistic regression analysis, however, found that only the occurrence of major vascular complications (OR 5.1, 95% CI 1.3-19.6; P = 0.018) and the number of pacing runs (OR 1.8, 95% CI 1.1-2.8; P = 0.025) independently predicted systemic inflammation.

Plausible but Perhaps Not Actionable

Dr. Nickenig and colleagues point out that a “transient drop in total or regional blood flow with consecutive hypotension occurs during several steps of the [TAVR] procedure: in the initial phase during rapid pacing and [balloon valvuloplasty], deployment, post-dilatation, or repositioning of the valve prosthesis, and potentially as a consequence of vascular complications and/or major bleeding events.” Suboptimal perfusion may be at the root of systemic inflammation after TAVR, they explain, as is the case following cardiac surgery or MI.

In an e-mail communication, study coauthor Jan-Malte Sinning, MD, Rheinische Friedrich-Wilhelms-Universität Bonn, said that the development of systemic inflammation “could be easily identified by an increased leucocyte count [as early as] 4 hours after the TAVR procedure” or by assessing clinical parameters in the intensive care unit (ICU). Another approach would be to predict at-risk patients by measuring procalcitonin levels.

Dr. Sinning suggested that patients who develop inflammation “should be monitored very carefully in the ICU, especially with respect to the volume status, as these patients are at risk to develop acute kidney injury which contributes itself to postprocedural mortality. These patients benefit from an invasive hemodynamic monitoring after TAVR.

“Currently, strategies to prevent [systemic inflammation] and/or acute kidney injury in TAVR patients remain an important challenge, as both complications are associated with a dramatic increase in mortality and hospital resource utilization. Due to the multifactorial pathogenesis of [inflammation] in [TAVR] patients, every measure has to be taken to avoid or treat these [issues],” Dr. Sinning continued. There is no established anti-inflammatory treatment, he added, but options include restricting the use of blood transfusion to help “break the vicious circle of cytokine release and inflammation” and limiting the duration of procedure-related hypotension in the hopes of staving off the syndrome.

In a telephone interview with TCTMD, Stephen G. Ellis, MD, of the Cleveland Clinic (Cleveland, OH), agreed that systemic inflammation could plausibly occur in patients undergoing TAVR but was less certain about its fallout.

“CRP and a number of markers like IL-6 are known to go up with acute coronary syndromes, blood transfusion, surgery, and cancer, so I didn’t find it terribly surprising that they went up after TAVR,” he said, expressing skepticism that inflammation was the direct cause of elevated mortality 1 year later. “I think it may be a marker . . . rather than a cause of [bad outcomes], because it is already related to a number of things that imply high risk or adverse outcomes.”

And while CRP measurement and leucocyte count could be used “after TAVR to help us stratify patient risk,” he noted, the question is how to alter care in patients identified as having inflammation. Most are already on statins and aspirin, and steroids are not an option, Dr. Ellis said.

“It’s interesting. I’m just not quite sure what to do with the data,” he concluded.

 

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Source:
Sinning J-M, Scheer A-C, Adenauer V, et al. Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation. Eur Heart J. 2012;Epub ahead of print.

 

 

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