Cardiovascular Risk in Peripheral Artery Disease Patients Undergoing Endovascular Revascularisation (RISK)

According to the recommendations of the European Society of Cardiology, serial measurement of cardiac troponin before and after procedures with moderate or high peri-procedural risk is recommended in cardiovascular patients undergoing surgery or interventions, including lower extremity revascularization procedures. Peri-operative myocardial infarction/injury (PMI) is defined as an increase in troponin levels on postoperative day 1 or 2 above the reference range compared with the pre-procedural value. Most patients with PMI do not present with typical ECG changes or clinical symptoms suggestive of myocardial ischemia. Identification of PMI is clinically important, as studies have shown that PMI predicts worse cardiovascular outcomes. Patients with PMI have higher 30-day and 1-year mortality rates and a higher incidence of major adverse cardiovascular events. The incidence of PMI in patients with peripheral arterial disease (PAD) is approximately 20%, which is higher than that observed after non-cardiac surgery in the general population.

Only two studies have reported myocardial injury after endovascular revascularization treatment for peripheral arterial disease, specifically myocardial injury after non-cardiac surgery (MINS), which, unlike PMI, excludes non-ischemic causes. In patients with critical limb ischemia, PMI occurred in 25.5% of patients after the procedure and was associated with a 2.4-fold increase in mortality and a 2.9-fold increase in major adverse cardiovascular events within one year. In patients with intermittent claudication, PMI occurred in 2% of patients and was likewise associated with a worse prognosis, with a higher incidence of cardiac death, myocardial infarction, and urgent revascularization during a 2.4-year follow-up period (7% vs. 30.8%).

Current risk assessment recommendations prior to revascularization procedures also include measurement of BNP or NT-proBNP (N-terminal pro-B-type natriuretic peptide). Elevated levels are associated with poorer cardiovascular prognosis and may additionally help identify previously undiagnosed heart failure in patients with PAD. Previous studies have shown NT-proBNP to be a better predictor of perioperative cardiovascular risk than parameters obtained from standard echocardiographic examination.

However, emerging evidence suggests that newer and more advanced echocardiographic parameters, capable of detecting subclinical myocardial dysfunction, may provide additional prognostic value in cardiovascular risk stratification. In patients undergoing major non-cardiac surgery under general anesthesia, impaired preoperative left ventricular global longitudinal strain (LVGLS) demonstrated independent and incremental prognostic value for predicting mortality, acute coronary syndrome, and MINS within 30 days after surgery, whereas left ventricular ejection fraction did not.

Prognostic assessment in patients with PAD may potentially be further improved by evaluation of myocardial work (MW) echocardiographic parameters, although data on this topic are currently lacking. Furthermore, it remains unknown whether endovascular revascularization procedures influence heart rate variability (HRV), which is also an established prognostic marker.

We plan to enroll approximately 500 patients with PAD admitted to the Department of Vascular Diseases for endovascular revascularization treatment. In accordance with ESC recommendations, NT-proBNP levels will be measured at admission, while high-sensitivity cardiac troponin T/I (hs-cTnT/I) will be measured at admission and on the day after the procedure to assess the incidence of PMI. Participants will also undergo transthoracic echocardiography, primarily for assessment of LVGLS and myocardial work parameters. In addition, heart rate variability will be assessed before and after the procedure using a 5-minute high-resolution ECG recording (Cardiax device) obtained in the supine position.

At 30 days and 1 year after the procedure, the following primary outcomes will be recorded:

• Major adverse cardiovascular events (MACE), defined as a composite endpoint of myocardial infarction, stroke, unstable angina, or cardiovascular death;
• Major adverse limb events (MALE), defined as a composite endpoint of untreated loss of patency of the revascularized segment, repeat intervention on the revascularized segment, or above- or below-knee amputation of the revascularized limb;
• All-cause mortality. To enable future investigation of the potential mechanisms underlying the observed results, additional blood samples will be collected before and after the procedure for analysis of inflammatory and oxidative stress biomarkers. Furthermore, an additional preprocedural blood sample will be collected for genetic biomarker analysis. These samples will be stored frozen for subsequent analysis.