Canadian Journal of Anesthesia/Journal canadien d'anesthésie

, Volume 61, Issue 1, pp 12–18

Untreated preoperative depression is not associated with postoperative arrhythmias in CABG patients

  • Rita Katznelson
  • W. Scott Beattie
  • George N. Djaiani
  • Matthew Machina
  • Ronit Lavi
  • Vivek Rao
  • Shahar Lavi
Reports of Original Investigations

DOI: 10.1007/s12630-013-0051-3

Cite this article as:
Katznelson, R., Scott Beattie, W., Djaiani, G.N. et al. Can J Anesth/J Can Anesth (2014) 61: 12. doi:10.1007/s12630-013-0051-3
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Abstract

Purpose

The mechanism by which depression affects postoperative outcome may involve arrhythmias. The purpose of this study was to evaluate whether untreated depression is associated with an increased incidence of postoperative arrhythmias in patients undergoing coronary artery bypass graft surgery (CABG).

Methods

One hundred seven patients were assessed for signs of depression with the Prime-MD Patient Health Questionnaire (brief PHQ) one week before surgery and subsequently underwent Holter monitoring for 48-72 hr postoperatively. The incidences of atrial fibrillation (AF); supraventricular tachycardia (SVT); ventricular tachycardia (VT), defined as three or more consecutive beats at a cycle length less than 600 msec; ventricular fibrillation (VF); and average heart rate (HR) were recorded in patients with and without signs of depression.

Results

The incidence of preoperative untreated depression was 27% (29/107). Twenty patients had 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). The incidences of postoperative AF, SVT, and non-sustained VT in depressed and non-depressed patients were 37.9% vs 35.9%, respectively (P = 0.50), 34.4% vs 52.5%, respectively (P = 0.07), and 17.2% vs 37.1%, respectively (P = 0.04). The average (SD) postoperative HR was similar in both groups [95 (12) beats·min−1 in depressed patients and 92 (10) beats·min−1 in non-depressed patients, (P = 0.25)]. Multivariate regression analysis showed that older age, but not depression, was a risk factor for postoperative arrhythmia.

Conclusions

Preoperative untreated depression is not related to postoperative arrhythmia in the early postoperative period in patients undergoing elective CABG. This trial was registered at clinicaltrials.gov (number: NCT00622024).

La dépression préopératoire non traitée n’est pas associée à des arythmies postopératoires chez les patients subissant un PAC

Résumé

Objectif

Le mécanisme par lequel la dépression affecte le pronostic postopératoire pourrait impliquer des arythmies. L’objectif de cette étude était d’évaluer si une dépression non traitée était associée à une incidence accrue d’arythmies postopératoires chez les patients subissant un pontage aortocoronarien (PAC).

Méthode

Cent sept patients ont été évalués pour déterminer s’ils présentaient des signes de dépression à l’aide du Questionnaire Prime-MD Patient Health (le PHQ court) une semaine avant leur chirurgie, puis ils ont été monitorés avec un Holter cardiaque durant 48 à 72 h après leur opération. Les incidences de fibrillation auriculaire (FA); de tachycardie supraventriculaire (TSV); de tachycardie ventriculaire (TV), définie en tant que trois battements consécutifs ou plus à une durée de cycle inférieure à 600 msec; de fibrillation ventriculaire (FV) et la fréquence cardiaque (FC) moyenne ont été enregistrées chez les patients avec et sans signes de dépression.

Résultats

L’incidence de dépression préopératoire non traitée était de 27 % (29/107). Vingt patients souffraient de dépression légère (score sur le PHQ court de 5-9), sept patients de dépression modérée (score de 10-14), et deux de dépression grave (score de 20). Les incidences de FA, de TSV et de TV non soutenue chez les patients déprimés et non déprimés étaient de 37,9 % vs. 35,9 %, respectivement (P = 0,50), 34,4 % vs. 52,5 %, respectivement (P = 0,07), et 17,2 % vs. 37,1 %, respectivement (P = 0,04). La FC postopératoire moyenne (ÉT) était semblable dans les deux groupes [95 (12) battements·min−1 chez les patients déprimés et 92 (10) battements·min−1 chez les patients non déprimés, (P = 0,25)]. L’analyse de régression multivariée a montré qu’un âge avancé, et non la dépression, était un facteur de risque d’arythmie postopératoire.

Conclusion

La dépression préopératoire non traitée n’est pas liée à l’arythmie postopératoire en début de période postopératoire chez les patients subissant un PAC non urgent. Cette étude a été enregistrée au numéro ClinicalTrials.gov NCT00622024.

Preoperative depression is common among patients undergoing heart surgery13 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.1,69

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.1417

Arrhythmia occurs frequently in patients with depression, irrespective of the presence of coronary artery disease.1823 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,2329 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,3540 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).
https://static-content.springer.com/image/art%3A10.1007%2Fs12630-013-0051-3/MediaObjects/12630_2013_51_Fig1_HTML.gif
Figure

Protocol flow diagram

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

 

Suspected depression*

No depression

P value

(n = 29)

(n = 78)

Age (yr)

63.0 (9.6)

64.6 (9.4)

0.45

Sex (female)

8 (27.5%)

2 (2.5%)

0.004

BMI (kg·m−2)

27.7 (4.4)

28.5 (5.6)

0.5

Preoperative heart rate (beats·min−1)

63 (10)

68 (15)

0.03

Preoperative pulse Pressure (mmHg)

54 (13)

57 (18)

0.27

Hypertension

23 (79.3%)

54 (69.2%)

0.3

Diabetes

8 (27.5%)

35 (44.8%)

0.12

PVD

4 (13.8%)

9 (11.5%)

0.7

Previous MI

4 (13.8%)

28 (35.9%)

0.03

Stroke

1 (3.4%)

7 (8.9%)

0.4

COPD

1 (3.4%)

4 (5.1%)

1.0

Alcohol use ≥ 2 drinks/day

29 (6.9%)

4 (5.1%)

0.6

Beta blockers

21 (72.4%)

47 (60.2%)

0.27

Ca channel blockers

4 (13.8%)

14 (17.9%)

0.7

Preoperative Hb (g·dL−1)

138 (13)

144 (12)

0.05

Preoperative creatinine (μM)

73 (38)

88 (22)

0.01

Preoperative potassium (mEq·L−1)

4.2 (0.3)

4.1 (0.4)

0.2

Data are expressed as mean (SD) or number (%). BMI = body mass index; Hb = hemoglobin; PVD = peripheral vascular disease; MI = myocardial infarction; COPD = chronic obstructive pulmonary disease. *Prime-MD Patient Health Questionnaire score ≥ 5

Table 2

Intraoperative data

 

Suspected Depression*

No depression

P value

(n = 29)

(n = 78)

Number of coronary artery grafts, median (min; max)

3 (1;4)

3 (1;4)

0.9

CPB time (min)

78 (28)

79 (23)

0.8

Aortic cross clamp time (min)

63 (27)

61 (19)

0.7

Intraoperative dopamine

12 (41.3%)

18 (23%)

0.06

Intraoperative epinephrine

1 (3.4%)

7 (8.9%)

0.3

Intraoperative norepinephrine

5 (17.2%)

17 (21.8%)

0.6

Intraoperative vasopressin

1 (3.4%)

4 (5.1%)

0.6

Intraoperative milrinone

0

2 (2.5%)

0.5

Data are expressed as mean (SD) or number (%) unless otherwise indicated. CPB = cardiopulmonary bypass. *Prime-MD Patient Health Questionnaire score ≥ 5

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

 

Suspected depression*

No depression

P value

(n = 29)

(n = 78)

Heart rate (average) (beats·min−1)

95 (12)

92 (10)

0.25

AF

11 (37.9%)

28 (35.9%)

0.5

AF time > 3 min

8 (27.5%)

13 (16.7%)

0.27

SVT

10 (34.4%)

41 (52.5%)

0.07

VT

5 (17.2%)

29 (37.1%)

0.04

All arrhythmias

20 (68.9%)

69 (88.4%)

0.02

Postoperative amiodarone

9 (31%)

26 (33.3%)

0.2

Postoperative beta blockers

21 (72.4%)

48 (61.5%)

0.12

Postoperative Ca channel blockers

1 (3.4%)

2 (2.5%)

0.6

Cardioversion

0

2 (2.5%)

0.5

Postoperative norepinephrine

10 (34.4%)

25 (32.0%)

0.49

Postoperative epinephrine

1 (3.4%)

6 (7.7%)

0.39

Postoperative dopamine

13 (33.3%)

37 (47.4%)

0.03

Postoperative vasopressin

2 (6.9%)

9 (11.5%)

0.38

Postoperative milrinone

0

2 (2.6%)

0.5

Data are expressed as mean (SD) or number (%). AF = atrial fibrillation; SVT = supraventricular tachycardia; VT = ventricular tachycardia. *Prime-MD Patient Health Questionnaire score ≥ 5

Table 4

Multivariate logistic regression for postoperative arrhythmias (ventricular and supraventricular)

 

Odds Ratio

Standard Error

z score

P value

Confidence intervals

Suspected Depression*

0.27

0.23

−1.48

0.1

0.05 (1.5)

Age

1.13

0.05

2.63

0.008

1.03 (1.24)

Female sex

1.9

2.8

0.47

0.5

0.12 (32.6)

CPB time > 90 min

1.8

1.6

0.6

0.5

0.27 (1.6)

Preoperative Ca channel blockers

3.1

4.5

0.93

0.3

0.25 (45)

Preoperative beta blockers

0.8

0.8

−0.2

0.8

0.1 (6.0)

Postoperative dopamine

1.7

1.6

0.59

0.6

0.27 (10.7)

CPB = cardiopulmonary bypass. *Prime-MD Patient Health Questionnaire score ≥ 5

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.3538 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.

Funding

Dean’s Fund, University of Toronto, Canada.

Competing interests

None declared.

Copyright information

© Canadian Anesthesiologists' Society 2013

Authors and Affiliations

  • Rita Katznelson
    • 1
  • W. Scott Beattie
    • 1
  • George N. Djaiani
    • 1
  • Matthew Machina
    • 1
  • Ronit Lavi
    • 2
  • Vivek Rao
    • 3
  • Shahar Lavi
    • 4
  1. 1.Department of Anesthesia and Pain ManagementToronto General HospitalTorontoCanada
  2. 2.Department of Anesthesia and Perioperative MedicineUniversity of Western OntarioLondonCanada
  3. 3.Department of Cardiac SurgeryToronto General HospitalTorontoCanada
  4. 4.Division of Cardiology, Department of MedicineUniversity of Western OntarioLondonCanada