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

Prognostic Markers of Cardiovascular Risk in Peripheral Artery Disease Patients Undergoing Endovascular Revascularisation

This study will investigate heart-related complications in patients with peripheral arterial disease (PAD) undergoing endovascular revascularization procedures to improve blood flow in the legs. Previous studies have shown that some patients develop silent heart injury after these procedures, even without symptoms, and that this may be associated with worse long-term outcomes.

Approximately 500 patients will be included in the study. Blood tests for cardiac biomarkers, including high-sensitivity troponin and NT-proBNP, will be performed before and after the procedure. Participants will also undergo ultrasound examination of the heart to assess heart function, including advanced measures that may detect early or subtle heart damage. In addition, heart rate variability will be measured using a short electrocardiogram recording.

Patients will be followed for 30 days and 1 year after the procedure to assess the occurrence of major cardiovascular events, limb-related complications, and death. Additional blood samples will be collected and stored for future analysis of inflammation, oxidative stress, and genetic markers that may help explain the mechanisms associated with heart injury and prognosis in these patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Ischemia; Cardiovascular Diseases; Myocardial Injury; Peripheral Arterial Disease; Biomarkers; Echocardiography; Troponin; Endovascular Procedures; NT-proBNP

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of approximately 500 adult patients with Peripheral Arterial Disease who are admitted to the University Medical Centre Ljubljana for elective or urgent endovascular revascularization treatment of lower extremity peripheral arterial disease, including patients with intermittent claudication and chronic limb-threatening ischemia. Participants will be recruited consecutively during hospitalization and enrolled after providing written informed consent.

Description

Inclusion Criteria:

• Patients with Peripheral Arterial Disease admitted to the University Medical Centre Ljubljana for endovascular treatment of lower extremity peripheral arterial disease.
• Ability and willingness to provide written informed consent after explanation of the purpose and procedures of the study.

Exclusion Criteria:

• Active malignant disease.
• End-stage renal disease requiring dialysis treatment.
• Previous enrollment in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
peripheral arterial disease patients; peripheral arterial disease patients following endovascular revascularization procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACE)	composite endpoint of myocardial infarction, stroke, unstable angina, or cardiovascular death	30 days and 1 year after the procedure
Major adverse limb events (MALE)	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	30 days and 1 year after the procedure
All-cause mortality	death from any reason	30 days and 1 year after the procedure

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Echocardiography; NT-proBNP; Peripheral arterial disease (PAD); Major adverse limb events (MALE); Cardiovascular risk stratification; Endovascular revascularization; Major adverse cardiovascular events (MACE); Peri-operative myocardial injury (PMI); High-sensitivity cardiac troponin (hs-cTnT/I); Left ventricular global longitudinal strain (LVGLS); Myocardial work (MW)
• Additional Relevant MeSH Terms: Vascular Diseases; Heart Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Cardiovascular Diseases; Peripheral Arterial Disease; Myocardial Ischemia
• Other Study ID Numbers: 0120-235/2025-2711-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: lack of time resources

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No