Preoperative depression is common among patients undergoing heart surgery1–3 and is an independent risk factor for short- and long-term mortality after valve4 or coronary artery bypass graft (CABG) surgeries.1,5,6 Patients with preoperative depression have longer hospital length of stay, higher rates of readmission, and increased need for repeat procedures.1,6–9

The mechanism by which depression affects outcome following cardiac surgery is not completely understood but may involve arrhythmias.10,11

Atrial and ventricular arrhythmias usually occur within three to four days after the surgery. The prevalence of postoperative supraventricular arrhythmias, particularly atrial fibrillation (AF), ranges from 25-60%.12 Malignant ventricular arrhythmias are less common and occur in 0.4-11% of patients.13 Postoperative arrhythmia is one of the most frequent early postoperative complications after CABG surgery and is associated with increased morbidity and mortality.14–17

Arrhythmia occurs frequently in patients with depression, irrespective of the presence of coronary artery disease.18–23 One of the plausible mechanisms explaining the relationship between depression and arrhythmia is autonomic dysfunction. Patients with depression have altered secretion of norepinephrine, a higher resting heart rate, low heart rate variability, and reduced baroreflex sensitivity,23–29 resulting in resting sinus tachycardia.25,26

There are numerous facts indicating a possible link between depression, arrhythmia, and outcome. Patients with coronary artery disease who are affected by depression have a higher prevalence of ventricular tachycardia (VT) and atrial fibrillation.18,23 Depression is associated with higher mortality rates after myocardial infarction, likely due to arrhythmias.30 Arrhythmias, such as premature ventricular contractions after myocardial infarction were associated with increased risk of sudden cardiac death in patients with depression.31 Symptoms of depression were associated with sudden death among placebo-treated patients but not among amiodorone-treated patients.31 Finally, depression predicted rates of defibrillation for VT/ventricular fibrillation (VF) among patients with implanted cardioverter-defibrillators.22

Despite the growing body of evidence that preoperative depression can increase the incidence of postoperative arrhythmia, two recently published reports in CABG patients did not support this hypothesis.32,33 Both studies used self-administered questionnaires to screen for preoperative depression and did not address whether the patients were treated for their depression symptoms.

Therapeutic options for depression include antidepressant medications, electroconvulsive therapy (ECT), transcranial magnetic stimulation, vagus nerve stimulation, deep brain stimulation, and psychotherapy.34 Each option or their combination can potentially affect the incidence of arrhythmia in rather unpredictable ways. Antidepressants, ECT, and vagus nerve stimulation have possible arrhythmogenic effects,35–40 yet, psychotherapy, such as biofeedback41 and cognitive behaviour therapy,42 can decrease the incidence of arrhythmia in cardiac patients.

The purpose of the current study was to evaluate whether untreated depression symptoms are associated with an increased incidence of postoperative arrhythmias in patients undergoing CABG.

Methods

This prospective observational study included patients undergoing elective CABG surgery. The study was approved by The University Health Network Research Ethics Board.

The study took place from August 2008 until August 2011 and included 120 consecutive patients. All participants provided informed consent. Inclusion criteria were patients undergoing elective CABG and aged 18-75 yr. Exclusion criteria were history of arrhythmias (AF, supraventricular tachycardia [SVT], VT, VF, permanent pacemaker, and/or defibrillator), history of psychiatric disorders (schizophrenia, mania, psychosis), treatment for depression in the last six months prior to surgery, pulmonary hypertension, and left ventricular ejection fraction < 40%.

One week before surgery, a trained research assistant assessed patients in the anesthesia preoperative clinic for signs of depression using the brief version of Prime-MD Patient Health Questionnaire (brief PHQ). The depression module of the brief PHQ scores each of the nine DSM-IV depression criteria as “0” (not at all) to “3” (nearly every day). Scores of 5, 10, 15, and 20 represent mild, moderate, moderately-severe, and severe depression, respectively.43 The brief PHQ is a screening tool for depression symptoms recommended by the American Heart Association to identify depression in cardiac patients.44 Patients with a PHQ score ≥ 10 were referred to psychiatry consult postoperatively.

Starting immediately after surgery, Holter monitoring was applied for 48-72 hr. Holter electrocardiogram (ECG) recordings were scanned by a MARS®8000 Arrhythmia Review Station (Wipro GE Healthcare) and interpreted by a Holter technician and a cardiologist who were blinded to the results of the depression assessment.

The primary outcome was the proportion of patients with postoperative ventricular or supraventricular arrhythmias. The following arrhythmias were recorded: number and frequency of episodes of AF, SVT, VT (defined as three or more consecutive beats at a cycle length less than 600 msec), and VF, and average heart rate.

Based on the psychiatric assessment, all patients were divided into two groups: patients with signs of depression (depression score ≥ 5) and patients without signs of depression (depression score < 5). The incidence of postoperative arrhythmias was compared between the groups.

Sample size calculation

Our sample size was based on an incidence of post CABG atrial fibrillation of 40% in patients with no depression.12 Although the incidence of depression in patients with coronary artery disease before CABG may be 40%,45 we made a conservative assumption that only 25% of our patients would have preoperative depression.

A sample size of 108 patients (unequal n in the two groups, 25% of patients having untreated depression) has 80% power to detect a relative risk of 1.77 with a significance level of 0.05.

We estimated an attrition rate of 10%; therefore, the final sample size was 120 patients.

Statistical analysis

A simple 2 x 2 contingency table was constructed to evaluate the presence of ventricular and /or supraventricular arrhythmias (dichotomous outcome) based on the Holter monitor assessment after surgery in patients with and without untreated depression.

Single predictor and multivariable logistic regression models were used to calculate the effect of preoperative untreated depression on postoperative arrhythmia. Untreated depression and other variables shown to have marginal association (P < 0.20) in the single predictor analysis were included in the multivariable model. The following variables were included in the multivariable model: age, sex, preoperative use of beta- and calcium channel blockers, cardiopulmonary bypass time, postoperative use of inotropic agents, and depression scores. Stata® ver. 12.1 (StataCorp LP, College Station, TX, USA) was used to analyze the data.

Results

One hundred seven patients completed the study (Figure). The incidence of preoperative untreated depression was 27% (29/107). Twenty patients were found to have mild depression (brief PHQ score of 5-9), seven patients had moderate depression (a score of 10-14), and two patients had severe depression (a score of 20).

Figure
figure 1

Protocol flow diagram

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The depression group included more females, and the patients in this group had lower hemoglobin and creatinine levels. Patients without signs of depression had a higher preoperative heart rate and a higher incidence of preoperative myocardial infarction (Table 1). There was no difference between groups in surgical characteristics or in the incidence of intraoperative use of inotropes and vasoactive drugs (Table 2).

Table 1 Baseline characteristics
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Table 2 Intraoperative data
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None of the patients developed sustained VT or VF. The incidence of non-sustained VT was 31.8%, and the incidence of postoperative atrial fibrillation was 36.4%.

Overall, there were more arrhythmias in the no depression group. There was no difference between groups in the incidence of postoperative atrial fibrillation and supraventricular arrhythmias (Table 3). None of the patients developed sustained VT or VF, but the incidence of non-sustained VT was higher in the patients without depression. Multivariate logistic regression analysis showed that preoperative depression is not associated with postoperative arrhythmia. The only risk factor for postoperative arrhythmia was older age (Table 4). The c statistic, estimate of the area under the receiver operating characteristic curve, was equal to 0.8.

Table 3 Postoperative arrhythmia
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Table 4 Multivariate logistic regression for postoperative arrhythmias (ventricular and supraventricular)
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Discussion

The results of the present study show that untreated preoperative depression symptoms and postoperative arrhythmia are frequent conditions in patients undergoing elective CABG. Preoperative untreated depression was not a predictor of postoperative arrhythmias in this patient cohort.

In fact, we found that patients without depression had a slightly higher incidence of postoperative arrhythmia compared with patients with signs of depression.

Furthermore, the resting preoperative heart rate (a marker of autonomic dysfunction) was slightly higher in patients without preoperative depression. There was no significant difference between the two groups in the need for inotropes and vasopressors intra- and postoperatively. Although the incidence of preoperative depression in our study was in the same range as previously reported,9 only nine patients fulfilled the criteria for moderate-severe depression. Therefore, the majority of patients in our cohort with mild depression symptoms simply did not reach the trigger threshold for autonomic dysfunction and neurotransmitter imbalance contributing to postoperative arrhythmia.

We excluded patients who were at high risk for postoperative arrhythmia. These included patients with a history of arrhythmia prior to surgery, poor left ventricular function, and pulmonary hypertension. The incidence of postoperative arrhythmia (AF and non-sustained VT) in the current cohort was similar to that in previous reports.13,17,46

One of the mechanisms explaining the association between depression and arrhythmia is the arrhythmogenic effect of antidepressant medications. Both tricyclic antidepressants and selective serotonin reuptake inhibitors may prolong the QT interval, affect heart rate variability, and cause arrhythmias.35–38 In addition, non-pharmacological modalities, such as ECT and vagus nerve stimulation, can trigger arrhythmias by affecting the QT interval or causing heart block.39,40 To avoid this confounding factor, patients who were treated for depression were excluded from our study. Similar to previous studies, we confirmed that older age is an independent risk factor for postoperative arrhythmia and that there was no positive association between depression and arrhythmia in patients with coronary artery disease.

A recent report by Turagam et al.47 showed that patients who survived sudden cardiac death and have a history of depression are not at higher risk of recurrent arrhythmia and death than those with no history of depression.

In a study by Beresnevaite et al.,32 109 male patients undergoing CABG were evaluated for preoperative depression and postoperative complications. They did not find any association between preoperative depression and early postoperative complications, including arrhythmia. The authors did not elaborate on their definition of postoperative arrhythmia or on the diagnostic criteria they used. In a study by Tully et al.,33 222 patients undergoing cardiac surgery were assessed for preoperative depression and anxiety. The primary outcome in this study was atrial fibrillation. The diagnosis was done with Holter monitoring applied for the first three postoperative days and thereafter with daily electrocardiograms until discharge. They found that anxiety, but not preoperative depression, had an association with postoperative atrial fibrillation. The authors did not comment on ventricular arrhythmias in their patient cohort. As previously mentioned, there was no discussion in any of these studies regarding the presence or absence of preoperative antidepressant therapy in the studied patients.

The results of our study extend the prior observations. Ours is a novel study using Holter monitoring specifically to diagnose the incidence of both supraventricular and ventricular postoperative arrhythmia in patients screened preoperatively for untreated depression. Therefore, we consider our results to be robust enough to conclude that untreated preoperative depression symptoms are not associated with postoperative arrhythmias.

The definition of depression was based on the results of a brief PHQ, which is a screening tool to identify patients with high risk for depression. Although high scores of the brief PHQ have high specificity and sensitivity for major depression, it cannot substitute psychiatric assessment for clinical diagnosis of depression. We did not perform a formal psychiatric examination in our patients and, therefore, our findings should be limited to only those patients defined as high risk for depression. The Holter monitor was applied for only 48-72 hr, and thus, there may have been arrhythmias after this period. Nevertheless, the incidence within the first 48-72 hr was high enough to confirm our findings. We included all types of arrhythmias in our study, some with a very short duration; therefore, some of the recorded arrhythmias are less likely to be clinically significant.

The results of our study cannot be applied to patients with a known history of arrhythmia and those who were treated with antidepressant medications or other therapeutic modalities in the perioperative period.

Although preoperative depression is a known independent risk factor for postoperative morbidity and mortality, it is unlikely that the negative effect of untreated depression symptoms on postoperative outcomes is related to arrhythmia in the early postoperative period.