Study design

This is a longitudinal three arm, randomized clinical trial, investigating the effect of different pre-surgery interventions on 6 months follow-up assessments in patients undergoing heart surgery (see CONSORT flow chart Fig. 1; full description of study design see [16]). We hypothesized that optimizing patient outcome expectations improves long-term outcome even after highly invasive interventions such as heart surgery. After study inclusion, patients were either randomized to an expectation optimization group (EXPECT), or to an emotional support group (SUPPORT), or to SMC preparation for the surgery (for short descriptions of interventions, see below). Clinical outcomes are compared between baseline and 6 months follow-up; immune parameters are also reported for direct surgery-associated changes (see below).

Fig. 1 Flow chart (CONSORT). Criteria mentioned in the “Baseline” row and “Analysis” row were reasons for exclusion of the patient from data analyses Full size image

Participant enrollment

The study took place at the Department of Cardiovascular Surgery, Heart Center, in collaboration with the Division of Clinical Psychology, Philipps University Marburg. Patients on the waiting list of the Heart Surgery Center were contacted before hospital admission. Inclusion criteria were adults older than 18 years who were scheduled for elective on pump CABG or CABG combined with valve surgery. Further inclusion criteria were ability to give informed consent and sufficient fluency in German. The interventions were introduced as two additional, slightly different brief psychological interventions, both aimed at improving coping with CABG. Exclusion criteria were the presence of a serious comorbid non-cardiac medical condition or psychiatric condition that substantially affected disability. Current psychiatric condition was assessed with the standardized interview structured clinical interview for DSM-IV diagnoses [17]. All participants gave written informed consent. Data collection lasted from April 2011 to May 2015.

Out of 249 patients approached for participation, 72 (28.9%) declined because of motivational reasons, including travel problems to attend the study appointments. Patients who agreed to take part in the study were significantly younger (t(157) = 3.31; P = 0.001), while sex ratios were comparable to patients who declined [18]. Two patients died before admission to the hospital, while 24 patients did not fulfill the inclusion criteria (Fig. 1). Thus, we started with an ITT sample of 124 patients (87% only CABG; 13% CABG plus heart valve replacement). Follow-up assessments were completed by 108 patients at 6 months follow-up (88.5% of baseline sample; 87% of ITT sample). Seven patients died post-surgery (two in SMC, two in SUPPORT, three in EXPECT condition).

While the study design was not changed from protocol, sample size calculation had to be adapted from initial calculations due to slower than anticipated recruitment into the trial. The sample size was adjusted to 124, thereby ensuring that this is still able to detect at least moderate effects (Cohen’s d > 0.30; alpha = 0.05; clinically meaningful difference in pain disability index > 4) with a power of 85%. Considering the Helsinki recommendation that trials investigating innovative interventions should not be oversized, this was considered acceptable.

Outcome variables

The predefined primary outcome variable according to the study protocol [16] was disability 6 months after surgery. We used a modified version of the Pain Disability Index, which was adapted for cardiology patients. This scale assesses disability in seven areas of life (family, job, social activities, etc.; ratings from 0 to 10) caused by the major health problem. It offers the opportunity to compare ratings with general population data [19], and results in a disability total score.

Secondary outcome variables addressed quality of life (QoL), fitness for work, physical activity, cardiac anxiety, and mental health. Health-related QoL was assessed by the Short Form Health Survey which has two subscales of QoL, namely physical and mental QoL [20]. Fitness for work was assessed asking patients the amount of time they feel able to work per week (in hours). We also assessed physical activity with the International Physical Activity Questionnaire (IPAQ), which allows the computation of metabolic equivalents of physical exercise [21]. Depression and anxiety were assessed by Hospital Anxiety and Depression Scale [22]. We also assessed cardiac specific anxiety using the Cardiac Anxiety Questionnaire [23]. This scale asks for concerns associated with the experience of cardiac sensations (e.g., after palpitations). Medical outcome variables such as readmission rates, adverse cardiac events after CABG, and acceptability of psychological interventions were also evaluated.

As a manipulation check measure, patient expectations about outcome and personal control beliefs were assessed using subscales of the Expected Illness Perception Questionnaire, which is based upon the Illness Perception Questionnaire [24]. This scale assesses patient expectations about their illness 6 months after surgery. Outcome expectations were assessed by the three items from the “treatment control subscale”, such as “6 months after CABG surgery, the surgery has cured my coronary disease”. Expected personal control beliefs were assessed by the four items from the Expected Illness Perception Questionnaire “personal control subscale”, such as “6 months after CABG surgery, there is a lot I can do myself to control my symptoms”.

As biological markers of the recovery process, immune parameters (interleukin 6 and 8 (IL-6, IL-8), tumor necrosis factor TNF-alpha, C-reactive protein (CRP)) were analyzed from blood samples. They were obtained at baseline, pre-surgery, 6–8 days post-surgery, and at follow-up, standardized at 2:00 PM to control for diurnal variations. Plasma for CRP and cytokine measurements was separated by centrifugation and stored at −80 °C until analysis. Plasma levels were analyzed by flow cytometry using bead-based assays (Bio-Plex Pro Human Cytokine Assays, Bio-Rad Laboratories, Hercules, CA, USA).

Medical status

Medical status was either assessed directly by physicians of the university hospital, or gathered from the patients’ medical records. It included the New York Heart Association Classification, EuroSCORE II (European System for Cardiac Operative Risk Evaluation [25]), left ventricular ejection fraction (LVEF), comorbid medical conditions, body mass index, smoking status, and history of myocardial infarction.

Procedure

The first assessment took place 1 week before surgery, either at home or in the university department. This was followed by the first in-person session of the psychological intervention, two phone calls, admission to the hospital, and second in-person session with subsequent assessments of psychological variables, on the day before surgery. Follow-up assessments took place 6 months after surgery. Further characteristics of the study sample can be found in Table 1. Further details of the study design are reported elsewhere [16].

Table 1 Demographical, medical and psychological characteristics at baseline of patients receiving Standard Medical Care (SMC; 44), Supportive Intervention (SUPPORT; 39) or Expectation Manipulation Intervention (EXPECT; 39) Full size table

Assignment to treatment arms followed a stratified permuted block randomization procedure with a block size of 9. Stratification criteria were age (above or below 65 years) and New York Heart Association class (1,2 versus 3,4) to control for differences in cardiac status. Random procedure was defined using an internet program (WINPEPI) before first-patient-in by JL, enrollment of patients was initiated by a study nurse being blind with regards to treatment condition. Allocation concealment was verified using closed envelopes including group allocation information that were handed over to the therapist after inclusion of a new patient. Surgeons, hospital staff involved in patient care, and staff assessing treatment effects were blind to treatment condition.

Interventions

EXPECT and SUPPORT both encompassed the same amount of personal contact (two 50 min individual sessions pre-surgery, two 20 min phone calls pre-surgery, one 20 min booster phone call post-surgery). Treatment sessions were audiotaped to verify treatment adherence. The brief and focused format of the interventions was shown to be feasible in the cardiac surgery environment.

EXPECT (expectation manipulation intervention): This intervention focused on the development of realistic expectations about the benefits of surgery and the recovery process. Patients were encouraged to develop personal ideas and images about their future after surgery, including plans about activities and how they will enjoy their life afterwards (outcome expectations). Personally relevant steps and plans for the 6 months after surgery were recorded for patients. Additionally, patients received a booklet containing all relevant session information, including the work sheets and audio-CDs of their sessions. Finally, normal symptoms after surgery that could be expected were discussed, and differentiated from unlikely complications. Patient control expectations were enhanced by discussing ways in which they could manage unpleasant symptoms or sensations, and how they could positively influence the disease course after surgery.

An example may further illustrate this intervention. Many patients hoped to again be able to work in their garden after surgery. In the EXPECT intervention, these patients developed specific plans on how they would successfully be able to reassume gardening activities due to their expected increased exercise capacity following surgery: repotting small plants in the early stage, lawn mowing after some time, increasing to more demanding gardening tasks between 3–6 months after surgery. One patient imagined himself chopping wood in preparation for hosting a barbecue in his garden for his family.

SUPPORT: This attention control group received the same amount of therapist attention, but without targeting expectations. Therapists encouraged expressing emotions and anxieties about the anticipated surgery, and therapists used reflective listening techniques and expressed empathy. This therapy has been developed to include all so-called “common factors of psychotherapy”, such as empathy, therapist attention, and verbalization of emotions [26]. Patients in the SUPPORT group did not receive audio-CDs.

SMC: Like the patients of the other groups, these patients received the standardized informed consent procedure before surgery, and general medical care, but no additional psychological interventions. Assessments were identical.

Therapists: Pre-surgery interventions were provided by three psychologists (2 male, 1 female). All therapists were specifically trained and provided both types of interventions; they were additionally supervised by a senior psychotherapist to ensure treatment fidelity. Previous analyses confirmed treatment fidelity, and treatment satisfaction was similar between the two intervention groups [18].

Statistics

The primary hypotheses (better follow-up outcome in the EXPECT group) were analyzed using a linear mixed model with time, treatment group and time × treatment group interaction as fixed effects and a random intercept for subject specific effects with maximum likelihood estimation and autoregressive residual matrix. Compared to intention-to-treat analyses, this procedure provides better estimates for missing data using the full data sample (intention-to-treat sample), and addresses individual differences more adequately [27, 28]. Pattern of missing values is postulated to be random. We expected a significant interaction between intervention group and assessment time. Requirements of this procedure for data distribution were inspected according the Field’s recommendations [29]. If criteria for multivariate outliers were fulfilled (1 to 3 persons per group; Mahalanobis-distance criteria), preconditions for maximum likelihood estimations were violated, and data were not included. If significant interactions occurred, we report pre–post tests per group to indicate whether the specific group has improved, and we compared follow-up scores of pairwise groups controlling for baseline scores (two groups, two assessment points).

For immunological parameters, preconditions for multilinear analyses were checked, and log-transformation was used if data was extremely skewed and could not be used for calculating linear mixed models (this was the case for IL-6). Boxplots were used to check for outliers. Values greater/lower than three interquartile ranges from the upper/lower quartile were considered as missing values. This was the case for less than 5.4%.

All statistical analyses were run using SPSS Statistics 22. Tables report observed means for all variables, figures report estimated marginal means for selected variables to illustrate effects.