VISION Eyeballs Too-Low Troponin Values for MI, Injury After Cardiac Surgery

Postoperative levels of high-sensitivity cardiac troponin I (hs-cTnI) in cardiac surgery patients that indicate an increased risk of death within 30 days may be as much as 500 times higher than the thresholds set by consensus statements for estimating perioperative MI and myocardial injury risks, according to results of the international VISION cardiac surgery study.

Lead author P.J. Devereaux, MD (Population Health Research Institute, Hamilton, Canada), told TCTMD that the guidelines regarding troponin thresholds after surgery were influenced by use of creatine kinase-myocardial band (CK-MB) and non-high-sensitivity troponin assays and, as the study shows, simply do not apply to the high-sensitivity-troponin assays in use today.

“There's a risk that some people could be assumed to be having a problem after surgery, when in fact they're not, because the guideline recommendation for thresholds is so much lower than what we actually demonstrated in this study to be the thresholds associated with prognostic relevance,” Devereaux said.

In an editorial accompanying the study in the New England Journal of Medicine, James A. de Lemos, MD, and Michael Jessen, MD (both UT Southwestern Medical Center, Dallas, TX), say the investigation of nearly 14,000 patients suggests that myocardial injury after cardiac surgery is ubiquitous, and that only extremely large elevations in hs-cTnI are associated with an increased 30-day risk of mortality. They note that “independent validation is essential before clinical implementation, since any method that derives and assesses cutoff values in the same cohort will overestimate performance.”

Additionally, de Lemos and Jessen say the thresholds pertain only to the hs-cTnI assay, and “similar evaluation will be required for high-sensitivity cardiac troponin T and for high-sensitivity cardiac troponin I assays other than the one used in this study.”

To TCTMD, Devereaux said while he agrees about the need for similar high-quality studies of the other assays to ascertain thresholds specific to them, “I predict that they'll show very similar results . . . [many] times the upper limit of normal.”

Cardiac Surgery Outcomes

The Fourth Universal Definition of Myocardial Infarction (UDMI) recommends thresholds for diagnosis of perioperative MI of > 10 times the upper reference limit, while the Academic Research Consortium-2 endorses troponin ratios of 35 times the upper reference limit for diagnosis of perioperative MI with evidence of ischemia and ratios of 70 times the upper reference limit for diagnosis of myocardial injury in the absence of ischemia. A recent analysis of solely CABG patients found that the prognosis of patients with perioperative MI may very well depend on whether the UDMI or the Society for Cardiovascular Angiography and Interventions (SCAI) definition—derived from CK-MB—is used to define the events.

VISION enrolled patients from 12 countries who underwent surgeries between 2013 and 2019. By taking serial measurements of hs-cTnI, Devereaux and colleagues found that in the first day after isolated CABG or AVR, 97.5% of patients undergoing isolated CABG or AVR had a peak hs-cTnI measurement greater than 260 ng/L, which is more than 10 times the upper reference limit; 89.4% of patients had a peak troponin measurement of at least 910 ng/L, which is more than 35 times the upper reference limit; and 74.7% had a peak troponin measurement of at least 1,820 ng/L, which is more than 70 times the upper reference limit.

The rate of mortality at 30 days was 2.1%, and the rate of major vascular complication was just under 3%. The estimated threshold troponin value from day 1 postop associated with death within 30 days was 5,670 ng/L, which is 218 times the upper reference limit. By day 2 or 3, the estimated threshold troponin value was 1,522 ng/L, which is 59 times the upper reference limit.

In a prior study, focused on noncardiac surgery, Devereaux and colleagues found that elevated levels on another assay, high-sensitivity troponin T, in the hours and days postprocedure, was predictive of 30-day mortality. In fact, the only indicator in 93% of those with myocardial injury and short-term mortality was elevated troponins.

“Up ‘til now, the guidelines have only really focused on patients having CABG surgery. They have not informed patients having valve surgery or other heart surgeries. For the first time we're informing that,” Devereaux said. In addition to isolated CABG and AVR cases, VISION also enrolled those having other cardiac surgeries, including CABG or AVR in combination with another procedure. In that group, the estimated threshold troponin value associated with death within 30 days was 12,981 ng/L, which was 499 times the upper reference limit.

Devereaux said the findings should go a long way toward improving knowledge about how troponin biomarkers work in the setting of cardiac surgery and set the stage for a RCT to provide more data.

For de Lemos and Jessen, however, the results of VISION “provide limited help for clinicians evaluating patients after cardiac surgery.” They say uncertainty about underlying mechanisms and strategies for prevention or treatment of perioperative myocardial injury without infarction makes the diagnosis of it of limited value, “other than perhaps suggesting careful review of the surgical and postoperative course for unrecognized complications and closer follow-up with consideration of echocardiography.”

Devereaux disagreed.

“We need to get to a diagnosis, and at the moment, we're using lab tests but we're profoundly wrong in what is the threshold that should represent abnormal,” he said. “I really hope this is going to influence consensus documents. The Universal Definition of MI is probably the most influential document and it says you should use 10 times the upper limit of normal. Well, if we're showing that over 97% of patients have a troponin value well above that level, it tells you that that threshold is useless in this setting.”