CLINICAL RESEARCH: HEART RHYTHM DISORDER
Risk of Ventricular Arrhythmia After Implantable Defibrillator Treatment in Anxious Type D Patients
Krista C. van den Broek, PhD*,*,
Ivan Nyklí ek, PhD*,
Pepijn H. van der Voort, MD ,
Marco Alings, MD, PhD ,
Albert Meijer, MD, PhD and
Johan Denollet, PhD*
* CoRPS (Center of Research on Psychology in Somatic diseases), Tilburg University, Tilburg, the Netherlands
Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands
Department of Cardiology, Amphia Hospital, Breda, the Netherlands
Manuscript received February 9, 2009;
revised manuscript received March 30, 2009,
accepted April 26, 2009.
* Reprint requests and correspondence: Dr. Krista C. van den Broek, CoRPS, Tilburg University, Department of Medical Psychology, Room P612, P.O. Box 90153, 5000 LE Tilburg, the Netherlands (Email: CvdBroek{at}uvt.nl).
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Abstract
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Objectives: We sought to examine the combination of adverse psychological factors (anxiety, depression, and distressed or Type D personality) as a predictor of ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs).
Background: Little is known about the role of psychological factors and their clustering in the occurrence of life-threatening arrhythmias.
Methods: In this prospective study, 391 patients with an ICD (81% men, age 62.3 ± 10.4 years) completed anxiety, depression, and Type D personality scales at the time of implantation. The end point was occurrence of ventricular arrhythmia, defined as appropriate ICD therapies, in the first year after implantation.
Results: Ventricular arrhythmias occurred in 19% (n = 75) of patients. Increased symptoms of depression (p = 0.81) or anxiety (p = 0.31) did not predict arrhythmias. However, anxious patients with a Type D personality had a significantly increased rate of ventricular arrhythmias (21 of 71; 29.6%) as compared with other ICD patients (54 of 320; 16.9%; hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.14 to 3.13; p = 0.013). When controlled for the effects of sex, age, ischemic etiology, left ventricular dysfunction, prolonged QRS duration, and medication, anxious Type D patients (HR: 1.72; 95% CI: 1.03 to 2.89; p = 0.039) and secondary prevention patients (HR: 1.91; 95% CI: 1.14 to 3.20; p = 0.014) were at increased risk of ventricular arrhythmias.
Conclusions: Personality modulated the effect of emotional distress; anxiety predicted a 70% increase in risk of arrhythmia in Type D patients but not in other patients. Anxious Type D patients may be identified and offered additional behavioral support after ICD implantation.
Key Words: implantable defibrillator ventricular arrhythmias depression anxiety Type D personality
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Abbreviations and Acronyms
| | ACE = angiotensin-converting enzyme | | ATP = antitachycardia pacing | | BDI = Beck Depression Inventory | | CI = confidence interval | | DS14 = Type D scale | | HR = hazard ratio | | ICD = implantable cardioverter-defibrillator | | STAI = State Trait Anxiety Inventory |
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Implantable cardioverter-defibrillator (ICD) treatment provides an opportunity to study factors associated with ventricular arrhythmia as the most common cause of sudden cardiac death (1). Guidelines (2,3) advocate ICD implantation in patients who have survived life-threatening arrhythmias and in patients with severe left ventricular dysfunction. The use of an ICD does not prevent ventricular arrhythmias, but the ICD can terminate ventricular arrhythmias by antitachycardia pacing (ATP) or high-voltage shocks (4). However, patient selection for ICD implantation remains an important clinical issue, and better knowledge of risk factors for ventricular arrhythmias is needed (1,5). Moreover, sudden cardiac death caused by ventricular arrhythmias may still occur in a small proportion of ICD patients (6), which points out the importance of studying triggers and risk factors of ventricular arrhythmias after ICD treatment.
Clinical risk factors for ventricular arrhythmia include ischemic heart disease (1), New York Heart Association functional class III (7) or IV (8), previous ventricular arrhythmias (8), low left ventricular ejection fraction, QRS duration, and atrial fibrillation (9), but an unresolved issue is the role of emotional distress (10). Some studies found that shocked patients experience anxiety (11–14), depression (15), and impaired quality of life (16), although others (17–19) did not find this association. However, only a few studies have evaluated the role of emotional distress as precipitant of ventricular arrhythmias in patients with an ICD (20–23), with 2 studies (21,22) investigating emotional states as risk factors for arrhythmias, and 1 study (23) investigating acute emotional triggers.
Depression has been associated with ventricular arrhythmias (20), whereas others found that anxiety, but not depression and anger (21), or anger, but not sadness and anxiety (23), may trigger ventricular arrhythmias. These mixed findings indicate that other factors may modulate the effect of emotional distress, and evidence suggests that stable personality traits may increase the risk of emotion-triggered appropriate shocks in ICD patients (23). Of note, psychological risk factors do not occur in isolation (24) but rather tend to cluster together within cardiac patients to increase the risk of clinical events (25).
Therefore, the objective of this prospective study was to examine the extent to which Type D personality (i.e., the tendency to experience emotional and social distress) may modulate the association between anxiety/depression and ventricular arrhythmia. Previously, we have argued that research should focus on the interaction of psychological factors (24,26), and we have shown that clustering of Type D personality with other psychological factors increases the risk of adverse outcomes (12,27). In the present study, we examined the role of anxiety, depression, and their combination with Type D personality as predictors of ventricular arrhythmias during the 12-month period after ICD implantation, adjusting for sex, age, ICD indication, etiology, ejection fraction, QRS duration, and medical treatment.
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Methods
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Patient sample.
Patients who underwent ICD implantation between May 2003 and December 2006 were included from 2 referral hospitals in the Netherlands (Catharina Hospital, Eindhoven; Amphia Hospital, Breda). Inclusion criteria were implantation with an ICD and age between 18 and 80 years. Exclusion criteria were significant cognitive impairments (e.g., dementia), life-threatening comorbidities (e.g., cancer), and insufficient knowledge of the Dutch language. Patients who died during the 12-month follow-up period were not excluded from the analyses because these patients could also have experienced ventricular arrhythmias during their follow-up period. The study was approved by the Medical Ethics Committees of both participating hospitals. The study was conducted in accordance with the Helsinki Declaration, and all patients provided written informed consent.
Psychological measures.
Patients completed questionnaires on depressive symptoms, anxiety, and personality in the period between 1 day before ICD implantation and 3 weeks after ICD implantation.
Depressive Symptoms
The Beck Depression Inventory (BDI) is a 21-item self-report measure developed to assess the presence and severity of depressive symptoms (28). Each item is rated on a Guttmann scale from 0 to 3. The BDI is a reliable and valid measure of depressive symptomatology and the most frequently used self-report measure of depressive symptoms in cardiac patients. Scores 10 were used to indicate clinically relevant levels of depression (28,29).
Anxiety
The State Trait Anxiety Inventory (STAI) was used to assess general symptoms of anxiety (30). In the current study, we only used the state measure because the purpose of this study was to assess the current presence of symptoms of anxiety at baseline. The STAI state version consists of 20 items and each item is rated on a 4-point Likert scale from 1 (not at all) to 4 (very much so), with total scores ranging from 20 to 80, with higher scores indicating greater levels of state-anxiety. The STAI has adequate validity and reliability, with Cronbach's alpha ranging from 0.87 to 0.92 (30). To indicate clinically elevated levels of general anxiety, a cut-off of 40 was used, which was previously used in studies on ICD (31).
Type D Personality
The Type D scale (DS14) was used to assess Type D personality. Type D patients tend to experience increased negative emotions (e.g., worry and have a gloomy view of life) paired with emotional nonexpression (32). The DS14 contains 2 scales of 7 items each: Negative Affectivity (e.g., "I often feel unhappy") and Social Inhibition (e.g., "I am a closed kind of person") (32). Items are answered on a 5-point Likert scale, ranging from 0 (false) to 4 (true), with total scores ranging from 0 to 28 for both subscales. Patients scoring 10 on both subscales are classified as Type D (32,33). The DS14 has good reliability, with a Cronbach's alpha of 0.88 and 0.86 and 3-month test-retest reliability of 0.72 and 0.82 for Negative Affectivity and Social Inhibition, respectively (32). The DS14 is a stable personality measure during an 18-month period after an acute event (34), and scores are not confounded by cardiac disease severity or symptoms of anxiety and depression (34,35). Previous studies have shown an association between Type D personality and adverse clinical outcome, including mortality and morbidity (36–40).
Demographic and clinical variables.
Demographic variables included sex and age. Clinical variables included ICD indication (primary vs. secondary prevention), etiology (ischemic vs. nonischemic), severely decreased ejection fraction (left ventricular ejection fraction 35% vs. >35%), prolonged QRS duration (QRS duration 120 ms vs. <120 ms), and prescription of angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. These variables were obtained from medical records at baseline.
Ventricular arrhythmias.
Ventricular arrhythmias were defined by appropriate ICD therapies, either ATPs or shocks, which were delivered for ventricular tachycardia or ventricular fibrillation. Patients visited the center of implantation at regular intervals (mostly 3 or 6 months). During these visits arrhythmic events were recorded from the ICD and stored. Only a small number of patients did not visit the center of implantation but instead went to their own hospital. Therefore, these hospitals were contacted for information on arrhythmic events. None of the patients had remote monitoring systems. Because the study extended during a 12-month period, beginning with ICD implantation, we specifically included patients who already had their 12-month check-up in the hospital. Only the most aggressive treatment per episode was counted, meaning that if a patient experienced a ventricular arrhythmia for which first ATPs were delivered and then shocks, this episode was only counted as one shock. The occurrence of appropriate ATPs and shocks were obtained from medical records, with electrophysiologists judging the appropriateness of ICD therapies on the basis of electrocardiograms.
Statistical analyses.
Differences between groups were examined with a chi-square test (likelihood ratio where appropriate) for dichotomous variables and a t test for independent samples for continuous variables. To enhance clinical interpretability, anxiety and depression scores were dichotomized. As has been advocated previously, research on adverse outcomes should not only focus on the prognostic value of isolated psychological factors but also on the prognostic value of the interaction of these factors (24,25). This approach was adopted in our analyses. A series of univariable Cox regression analyses were performed to determine whether increased depressive symptoms, increased anxiety, Type D personality, and clustering of these factors predicted ventricular arrhythmias in the first year after ICD implantation. If a clustering of psychological factors was significant, the independent value of this clustering was tested first in a multivariable Cox analysis (enter method) that also included the main effects of these factors. Next, a multivariable Cox regression analysis (enter method) was performed, including the psychological predictor(s), and age, sex, ICD indication, etiology, severely decreased ejection fraction, prolonged QRS duration, and prescription of ACE inhibitors or beta-blockers.
Because multicollinearity may affect parameters in regression analyses, we performed a linear regression analysis to obtain tolerance and variance inflation factor (VIF) values (41), with a tolerance value <0.10 or a VIF value >10 indicating multicollinearity. The Kaplan-Meier method was used to graphically present the time to first ventricular arrhythmia, and the log-rank test was performed to test for significant differences between the groups. All data were analyzed with the use of SPSS version 16.0 for Windows (SPSS Inc., Chicago, Illinois), and p = 0.05 was used to indicate statistical significance.
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Results
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Patient characteristics.
Of the 432 patients who agreed to participate in the study, 391 (90.5%) patients were included in the analyses. Patients who were not included had missing data on self-report measures (n = 10) or clinical variables (n = 31). Included patients did not differ from excluded patients on any of the baseline characteristics. Table 1
shows demographic and clinical characteristics of the 391 patients included in the study, both for the total sample and stratified by occurrence of appropriate ICD therapies. The mean anxiety score (STAI) was 39.5 ± 11.7, and the mean depressive score (BDI) was 8.9 ± 6.7. Increased levels of anxiety were experienced by 47.8% (187 of 391) of patients and increased levels of depression by 35.3% (138 of 91) of patients. Finally, 23% (90 of 391) of patients were classified as a Type D.
Ventricular arrhythmias.
During the first year after implantation, 75 patients (19.2%) experienced ventricular arrhythmias with appropriate therapies, and 21 patients (4.6%) died. Of the 75 patients, 52.1% of patients only had appropriate ATP-only episode(s), 23.3% only had shock-only episodes, and 24.7% had both ATP-only and shock-only episodes. The median number of appropriate ICD therapies was 2, with a range from 1 to 1,100 episodes.
Psychological predictors of ventricular arrhythmias.
Univariable Cox regression analyses showed that secondary prevention (p = 0.004) was a significant predictor of occurrence of ventricular arrhythmia, but none of the other demographic or clinical variables were related to ventricular arrhythmia (Table 2). Regarding isolated psychological factors; increased anxiety (p = 0.31) and depression (p = 0.81) did not predict arrhythmias, but there was a trend for Type D personality (p = 0.079), with 29.6% (21 of 71) of Type D patients and 16.9% (54 of 320) of non-Type D patients having experienced ventricular arrhythmias.
Finally, Table 2 shows prognostic values of clustering of psychological factors. Clustering of anxiety and depression (p = 0.91) and depression and Type D personality (p = 0.18) did not significantly relate to arrhythmia. However, the combined presence of anxiety and Type D personality did significantly predict ventricular arrhythmias (p = 0.013).
Independent predictors of ventricular arrhythmias.
After controlling for anxiety and personality main effects, the anxiety x Type D interaction effect still was significant (hazard ratio [HR]: 2.09; 95% confidence interval [CI]: 1.01 to 4.39; p = 0.049), whereas the anxiety (p = 0.74) and Type D (p = 0.56) main effects were not. Hence, anxiety only had an impact when Type D personality was present. Stratification of patients in 4 distinct anxiety/Type D subgroups confirmed that anxious Type D patients (HR: 1.77; 95% CI: 1.02 to 3.06; p = 0.041) but not anxious non-Type D (p = 0.71) or nonanxious Type D (p = 0.43) patients had an increased risk of ventricular arrhythmia compared with the reference group (low anxiety and non-Type D). Because it was the clustering of anxiety and Type D that was associated with an increased arrhythmia risk, this combination was further examined in a multivariable model including demographic and clinical characteristics.
The tests for multicollinearity were negative, with all tolerance values ranging from 0.65 to 0.97 and VIF values from 1.03 to 1.54, which demonstrates the absence of multicollinearity. Hence, these variables did not have significant overlap, and they could be entered in the model at the same time.
In the multivariable Cox regression analysis (enter model), adjusting for sex, age, secondary prevention, nonischemic etiology, severely decreased ejection fraction, prolonged QRS duration, and prescription of ACE inhibitors or beta-blockers, clustering of anxiety and Type D personality remained significant with a 1.7-fold risk. In addition, secondary prevention was associated with a 1.9-fold risk to experience ventricular arrhythmias (Table 3).
Ventricular arrhythmias in anxious Type D patients.
Kaplan-Meier curves for the time to first ventricular arrhythmia for anxious Type D patients versus the other patients are shown in Figure 1. The log-rank test was significant (chi-square = 6.33, degrees of freedom = 1, p = 0.012), with anxious Type D patients experiencing earlier and more often ventricular arrhythmia as compared with other ICD patients.

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Figure 1 Kaplan-Meier Curve for Time to First Ventricular Arrhythmia in Type D Patients With Increased Anxiety (p = 0.012)
Other groups (blue line); anxious Type D patients (green line).
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Discussion
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In this prospective study, we examined the extent to which Type D personality may modulate the association between anxiety/depression and ventricular arrhythmia in the first year after ICD implantation. Clustering of increased anxiety at the time of implantation and having a Type D personality predicted arrhythmia, with its 1.7-fold independent risk being comparable with the 1.9-fold risk for secondary prevention patients.
Previous studies on psychological risk factors or triggers of ventricular arrhythmia in ICD patients yielded mixed findings, but none of these studies focused on a clustering of psychological risk factors. The findings of the present study support the notion that psychological factors may cluster in ICD patients which, in turn, increases the risk for adverse outcomes (24,26,27,42–46). More specifically, the finding that clustering of anxiety and Type D personality was a risk factor for adverse outcomes has also been described previously, including in ICD patients (12,27). Hence, the fact that the combined presence of negative emotional states and Type D personality incurs the highest adverse risk should be taken into account in future studies.
Results of the current study suggest that the relationship between psychological distress and morbidity and mortality (36–39,47) may be mediated by occurrence of ventricular arrhythmias. However, pathways or mechanisms linking emotions and personality traits in general and anxiety and Type D personality in particular to arrhythmias are not well known and should be explored further in future research. Stress may be associated with increased sympathetic tone and its detrimental effects on arrhythmia (48,49). Experimental studies have shown that general mental stress may induce increased T-wave alternans (50), which is associated with ventricular arrhythmias and death (51). Mental stress may also shorten the cycle length of ventricular tachycardia and consequently result in more difficult termination of this arrhythmia (52).
Secondary prevention was also significantly predictive for ventricular arrhythmias, whereas sex, age, nonischemic etiology, severely decreased ejection fraction, prolonged QRS duration, and prescription of ACE inhibitors or beta-blockers were not. The findings on indication, sex, and age are in line with results from previous research (8,21,53,54), although older and male patients may be at increased risk for ventricular arrhythmias (55). Because ischemic etiology, severely decreased ejection fraction, and prolonged QRS duration have been identified as precipitants of ventricular arrhythmias (1,9) whereas ACE inhibitors and beta-blockers have been found to have antiarrhythmic effects (56), it is difficult to explain the nonsignificant findings.
Screening for anxiety and Type D personality may be standardized in clinical practice because both factors have been associated with adverse outcomes in ICD patients (14,17,19,57,58). A recent review indicates that cognitive-behavioral therapy paired with exercise training may be most useful to diminish anxiety symptoms in ICD patients (59). Interventions for Type D personality may aim at changing coping styles for dealing with negative emotions. Because only a few studies have focused on psychological intervention in ICD patients (59) and because no study has investigated interventions for Type D patients, more research is needed on this topic, particularly regarding the role of supportive or medical therapy with respect to occurrence of ventricular arrhythmias in Type D patients.
Study limitations.
First, ventricular arrhythmias without therapy were not included. Second, because the cause of death is not known for most of the patients, it is unknown, although unlikely, whether death was attributable to ventricular arrhythmia. Third, anxiety was only measured at the time of implantation, which provided no information about the course of anxiety levels. However, a previous publication based on this sample suggested that baseline levels of anxiety did not differ from levels at 2 months after implantation (13). In addition, other studies suggest stability of anxiety levels (11,18).
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Conclusions
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This prospective study suggests that patients with both anxiety and a Type D personality, and patients with a secondary prevention are at increased risk to experience ventricular arrhythmias in the first year after ICD implantation. In clinical practice, anxious Type D patients should be identified and offered adequate support. Future studies may focus on the prevalence and prognostic value of clustering of psychological risk factors, but also on the role of supportive therapy in these patients. In addition, mechanisms and pathways linking anxiety and personality traits to ventricular arrhythmias need to be studied.
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Acknowledgments
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The authors thank Eefje Postelmans and Hidde Weetink for inclusion of the patients into the study and Martha van den Berg, MSc, Vivianne Sterk, MSc, Jolien Diekhorst, MSc, Marjan Traa, MSc, and Marie-Anne Mittelhaeuser for help with data management.
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Footnotes
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This study was supported by the Netherlands Organization for Scientific Research, The Hague, the Netherlands with a VICI grant (453-04-004) to Dr. Denollet. Dr. van der Voort has received speaker's fees from Medtronic. Dr. Alings reports that the Department of Clinical Electrophysiology has received unrestricted grants from Boston Scientific Nederland, Medtronic Nederland, and St. Jude Medical Nederland. Dr. Meijer has received lecturing fees, research support, and consultancy fees from Medtronic, Boston Scientific, and St. Jude Medical.
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