Five Years Follow-up of Neurological Outcome After Minimally Invasive Cardiac Surgery (FUNOMICS)

Five Years Follow-up of Neurological Outcome After Minimally Invasive Cardiac Surgery: Evidence for Late Cognitive Decline?

A monocenter observational study will be started to investigate postoperative cognitive dysfunction 5 years after minimally invasive cardiac surgery. Postoperative cognitive dysfunction will be evaluated in three groups: an endoscopic-CABG group (endo-CABG), a PCI (Percutaneous Coronary Intervention) group and a healthy control group. It is hypothesized that the endo-CABG group will show a stronger postoperative cognitive dysfunction compared to the PCI group and the healthy control group.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Cognitive Dysfunction; Surgery
• Intervention / Treatment: Diagnostic test: neurocognitive test battery

Detailed Description

Neurologic complications after cardiac surgery are a major cause of morbidity, prolonged hospital stay and increased costings. In selected cases, postoperative neurologic damage leads to permanent disability or decease of the patient. The American College of Cardiology and the American Heart Association classified neurological sequelae after cardiac surgery into type 1 and type 2. Type 1 morbidities are cardiovascular accident (CVA) and transient ischemic attack (TIA) whereas delirium and postoperative cognitive dysfunction (POCD) are classified as type 2 neurologic injury. Reported incidence of TIA/CVA after coronary artery bypass grafting surgery (CABG) is about 1.6-2%. Incidence of delirium and POCD is more difficult to quantify but ranges from 10-20% for delirium and 30-80% for POCD. Exact pathophysiology remains unclear but seems to be a complex interplay between macro- and microembolization, hypoperfusion and systemic inflammation. Also, preoperative neurologic state might play a role in these frequently comorbid cardiac patients. Some recent papers tried to improve neurologic outcomes by surgical, perfusionist or anesthetic adjustments, with limited success.

Literature concerning neurological complications after minimally invasive cardiac surgery (MICS) is scarce. However, this might be of special concern since in MICS, perfusion to the brain is routinely provided via retrograde flow. By consequence, the brain is possibly exposed to aortic atheroma located distal to the cerebral vessels. This is of special interest since embolic phenomena are identified as a trigger for neurologic failure after cardiac surgery. As the practice of MICS is globally expanding, observations on neurologic outcome after MICS are desirable, with screening for short-term as well as long-term complications.

An important reference article concerning late cognitive outcome after CABG surgery prospectively followed a cohort of 102 CABG patients up until five years after surgery. Patients were tested on eight neurocognitive domains at four moments in time: preoperatively, 3 months after surgery, one year after surgery and ultimately five years after surgery. Somewhat surprisingly, at follow-up on one year after surgery, patients performed significantly better at 5/8 cognitive domains without significant worse scores in the remaining domains. The authors note this finding might be attributed to the learning effect. However, on follow-up after five years, a significant decline in several domains was noted, both compared to one year follow-up as to baseline test results. Unfortunately, due to the lack of a (non-surgical) control group, the authors were unable to attribute this finding to CABG surgery itself or to the normal cognitive evolution in this aging, co-morbid population. Therefore, the group performed a nonrandomized longitudinal prospective study between conventional CABG patients, off-pump CABG (OPCAB) patients, nonsurgical coronary artery patients and healthy controls over a six-year follow-up period. They found a larger decline in all three patient groups compared to the healthy control group although none of the groups was substantially worse compared to baseline. As a result, some authors deduct postoperative neurologic decline is more dependent on preoperative patient state rather influenced by procedure-related factors. However, the influence of MICS and retrograde cardiopulmonary bypass (CPB) flow on long-term neurologic decline remains a question.

Between December 2016 and May 2018 the NOMICS trial (Neurologic Outcome after Minimally Invasive Cardiac Surgery) was performed in Jessa Hospitals, Belgium. Three groups were prospectively followed for three months: an endoscopic-CABG group (endo-CABG), a PCI (Percutaneous Coronary Intervention) group and a healthy age and gender matched control group. A battery of neurocognitive tests was performed in all patients and control group to establish the incidence of POCD. By performing these tests again five years after baseline, the investigators will be able to screen for late cognitive decline in a MICS population undergone retrograde arterial CPB flow. Also, because of the presence of two control groups, it might be able to discriminate if the earlier established late decline is typical to the surgical population, to the coronary artery disease (CAD) population and/or normal aging effect.

• Study Type: Observational
• Enrollment (Anticipated): 138

Contacts and Locations

Study Locations

• Belgium
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Recruiting
      • Jessa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects that participated in the NOMICS trail 5 years ago were invited to participate in the FUNOMICS trial.

Description

Inclusion Criteria:

• Minimally 18 years old
• Endo-CABG surgery 5 years ago (group 1)
• PCI surgery 5 years ago (group 2)
• Healthy volunteer 5 years ago (group 3)

Exclusion Criteria:

• Medical history of

  • Stroke or POCD
  • Symptomatic carotid disease
  • Dementia
  • Renal dysfunction (GFR < 30 ml/min)
  • Hepatic dysfunction (Aspartate aminotranspferase (SGOT/AST) or Alanine Amino Transpherase (SGPT/ALT) > 3x normal limits)
• History of drug, medication or alcohol abuse
• Language barrier or inability to communicate
• Physical abnormality that prevents performing the neurocognitive tests
• Surgical revision or presence of intra-operative major cardiac event (endo-CABG)
• Conversion to cardiac surgery of presence of major cardiac event (PCI)
• Simultaneous valve surgery
• Inability to travel to follow-up moment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Endo-CABG; Group that underwent retrograde arterial cardiopulmonary bypass flow.	Diagnostic test: neurocognitive test battery; Assessment of the incidence of late postoperative cognitive decline (LPOCD)
PCI; Surgical control group	Diagnostic test: neurocognitive test battery; Assessment of the incidence of late postoperative cognitive decline (LPOCD)
Healthy controls; Non-surgical control group	Diagnostic test: neurocognitive test battery; Assessment of the incidence of late postoperative cognitive decline (LPOCD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of Late postoperative cognitive dysfunction (LPOCD) at 5 years after surgery	A battery of four tests (Rey Auditory Verbal Learning Test (RAVLT), Trial Making Test (TMT A and B) and the Grooved Pegboard Test) mentioned by the 'statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery', published in 1995 supplemented with two additional tests (ie, the Welscher Adult Intelligence Scale (WAIS)-III digit span test and WAIS-III digit symbol-coding test) will be administered to determine the cognitive outcome. LPOCD is defined as an RCI (Reliable Change Index) ≤-1.645 (significance level 5%) or Z-score ≤-1.645 in at least two different tests.	through study completion, 5 year follow up after the previous study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the evolution of LPOCD until five years after the intervention patients (both endo-CABG as PCI) versus five years after baseline for healthy volunteers	A graph will be created for the group RCI values.	through study completion, 5 year follow up after the previous study
Assessment of predictors of poor neurological outcome after Endo-CABG	The predictive value of various demographic (ie, age and gender) and perioperative variables on neurological outcome after endo-CABG will be assessed. These variables were already collected for the NOMICS trial.	through study completion, 5 year follow up after the previous study
Assessment of interim medical events: need for additional surgery	The influence of interim medical events: the need for additional or redo CABG surgery and/or PCI surgery will be assessed.	through study completion, 5 year follow up after the previous study
Quality of life questionnaire	To compare quality of life (QoL) five years after endo-CABG and PCI the European Quality of Life-5 Dimensions (EQ-5D) questionnaire will be taken. This questionnaire gives a score between 0 and 1 with 1 being the best outcome and 0 being the worst outcome.	through study completion, 5 year follow up after the previous study
Patient satisfaction	Patient satisfaction five years after endo-CABG and PCI will be assessed with an 11-point numerical rating scale (where 0= not satisfied at all and 10= extremely satisfied).	through study completion, 5 year follow up after the previous study
Interim medical events: brain trauma, dementia, or stroke	Also formally diagnosed dementia, brain trauma and/or stroke (transient ischemic attack and cerebrovascular accident) will be recorded as interim medical event. In line with the 'statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery' a mood state assessment will be performed concurrently. Screening for depression will be performed with the Center for Epidemiological Studies Depression (CES-D) questionnaire.	through study completion, 5 year follow up after the previous study
Interim medical events: depression	In line with the 'statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery' a mood state assessment will be performed concurrently. Screening for depression will be performed with the Center for Epidemiological Studies Depression (CES-D) questionnaire.	through study completion, 5 year follow up after the previous study
Survival rate 5 years after endo-CABG and PCI		through study completion, 5 year follow up after the previous study

Collaborators and Investigators

• Sponsor: Jessa Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2022
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): January 30, 2023

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: f/2022/012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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