Risk of Ventricular Arrhythmia After Implantable Defibrillator Treatment in Anxious Type D Patients

Journal of the American College of Cardiology © 2009 by the American College of Cardiology Foundation Published by Elsevier Inc.

Vol. 54, No. 6, 2009 ISSN 0735-1097/09/$36.00 doi:10.1016/j.jacc.2009.04.043

Risk of Ventricular Arrhythmia After Implantable Defibrillator Treatment in Anxious Type D Patients Krista C. van den Broek, PHD,* Ivan Nyklı´cˇek, PHD,* Pepijn H. van der Voort, MD,† Marco Alings, MD, PHD,‡ Albert Meijer, MD, PHD,† Johan Denollet, PHD* Tilburg, Eindhoven, and Breda, the Netherlands 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 cardioverterdefibrillators (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. (J Am Coll Cardiol 2009;54:531–7) © 2009 by the American College of Cardiology Foundation

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 From the *CoRPS (Center of Research on Psychology in Somatic diseases), Tilburg University, Tilburg, the Netherlands; †Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands; and the ‡Department of Cardiology, Amphia Hospital, Breda, the Netherlands. 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. Manuscript received February 9, 2009; revised manuscript received March 30, 2009, accepted April 26, 2009.

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 emo-

532

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

tional states as risk factors for arrhythmias, and 1 study (23) investigating acute emotional ACE ⴝ angiotensintriggers. converting enzyme Depression has been associated ATP ⴝ antitachycardia with ventricular arrhythmias (20), pacing whereas others found that anxiety, BDI ⴝ Beck Depression but not depression and anger Inventory (21), or anger, but not sadness CI ⴝ confidence interval and anxiety (23), may trigger DS14 ⴝ Type D scale ventricular arrhythmias. These HR ⴝ hazard ratio mixed findings indicate that ICD ⴝ implantable other factors may modulate the cardioverter-defibrillator effect of emotional distress, and STAI ⴝ State Trait Anxiety evidence suggests that stable perInventory sonality 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. Abbreviations and Acronyms

Methods 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

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7

the period between 1 day before ICD implantation and 3 weeks after ICD implantation. 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 ⱖ10 were used to indicate clinically relevant levels of depression (28,29).

DEPRESSIVE SYMPTOMS.

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 ⱖ40 was used, which was previously used in studies on ICD (31).

ANXIETY.

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 ⱖ10 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 ⱕ35% vs. ⬎35%), prolonged QRS duration (QRS duration ⱖ120 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 TYPE D PERSONALITY.

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7

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.

533

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. Results 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 shockonly episodes, and 24.7% had both ATP-only and shockonly 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

Baseline and Clinical and Characteristics of 391 Patients Included in the Analyses Table 1 Demographic Baseline Demographic Clinical Characteristics of 391 Patients Included in the Analyses Appropriate Therapy for Ventricular Arrhythmia Characteristics

% (n)

No, %

Yes, %

80.6 (315)

81.0

78.7

Age (yrs), mean ⫾ SD

62.3 ⴞ 10.4

62.7 ⫾ 10.5

60.5 ⴞ 9.8

0.097

Males

p Value* 0.64

Secondary prevention

42.7 (167)

39.2

57.3

0.004

Nonischemic etiology

28.6 (112)

27.8

32.0

0.48

Severely decreased ejection fraction†

81.8 (320)

82.9

77.3

0.26

Prolonged QRS duration‡

58.8 (230)

59.8

54.7

0.42

No prescription of angiotensin-converting enzyme inhibitor

32.0 (125)

31.6

33.3

0.78

No prescription of beta-blocker

16.9 (66)

15.2

24.0

0.067

*p ⱕ 0.10 are presented in bold. †Ejection fraction ⱕ35%. ‡QRS duration ⱖ120 ms.

534

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7

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 ⫻ 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 nonType 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 Univariable VentricularofArrhythmias Table 2 Predictors UnivariableofPredictors Ventricular Arrhythmias Ventricular Arrhythmias Variables

HR

95% CI

p Value*

Demographic and clinical factors Male

0.91

0.52⫺1.58

0.74

Age

0.98

0.96ⴚ1.00

0.087

Secondary prevention

1.96

1.24ⴚ3.10

0.004

Nonischemic etiology

1.18

0.73⫺1.92

0.50

Severely decreased ejection fraction†

0.74

0.43⫺1.27

0.27

Prolonged QRS duration‡

0.81

0.52⫺1.28

0.37

No prescription of angiotensin-converting enzyme inhibitor

1.07

0.67⫺1.74

0.77

No prescription of beta-blocker

1.68

0.99ⴚ2.85

0.056

0.81

Isolated psychological factors Increased depressive symptoms

1.06

0.66⫺1.70

Increased anxiety

1.26

0.80⫺1.99

0.31

Type D personality

1.55

0.95ⴚ2.54

0.079

Depression ⫻ anxiety

1.03

0.62⫺1.72

0.91

Depression ⫻ Type D personality

1.49

0.83⫺2.66

0.18

Anxiety ⫻ Type D personality

1.89

1.14ⴚ3.13

0.013

Clustering of psychological factors

*p ⱕ 0.10 are presented in bold. †Ejection fraction ⱕ35%. ‡QRS duration ⱖ120 ms. CI ⫽ confidence interval; HR ⫽ hazard ratio.

Multivariable Predictors ofPredictors VentricularofArrhythmias Table 3 Multivariable Ventricular Arrhythmias Ventricular Arrhythmias HR

95% CI

Male

1.02

0.56⫺1.86

p Value*

Age

0.98

0.96⫺1.01

0.16

Secondary prevention

1.91

1.14ⴚ3.20

0.014

0.94

Nonischemic etiology

1.08

0.61⫺1.92

0.80

Severely decreased ejection fraction†

1.30

0.63⫺2.67

0.47

Prolonged QRS duration‡

0.98

0.59⫺1.61

0.92

No prescription of angiotensin-converting enzyme inhibitor

1.05

0.62⫺1.76

0.86

No prescription of beta-blocker

1.54

0.89⫺2.66

0.12

Anxious Type D cluster

1.72

1.03ⴚ2.89

0.039

*p ⱕ 0.10 are presented in bold. †Ejection fraction ⱕ35%. ‡QRS duration ⱖ120 ms. Abbreviations as in Table 2.

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 (chisquare ⫽ 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. Discussion 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

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7

Figure 1

Kaplan-Meier Curve for Time to First Ventricular Arrhythmia in Type D Patients With Increased Anxiety (p ⴝ 0.012)

Other groups (blue line); anxious Type D patients (green line).

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 betablockers 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

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

535

duration have been identified as precipitants of ventricular arrhythmias (1,9) whereas ACE inhibitors and betablockers 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 cognitivebehavioral 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). Conclusions 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. Acknowledgments

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. 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. E-mail: [email protected].

536

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

REFERENCES

1. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med 2001;345:1473– 82. 2. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006;48:e247–346. 3. Ezekowitz JA, Armstrong PW, McAlister FA. Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials. Ann Intern Med 2003;138: 445–52. 4. Glikson M, Friedman PA. The implantable cardioverter defibrillator. Lancet 2001;357:1107–17. 5. Glass L, Lerma C. Risk stratification for arrhythmic sudden cardiac death. Heart Rhythm 2006;3:1497–501. 6. Anderson KP. Sudden cardiac death unresponsive to implantable defibrillator therapy: an urgent target for clinicians, industry and government. J Interv Card Electrophysiol 2005;14:71– 8. 7. Whang W, Mittleman MA, Rich DQ, et al. Heart failure and the risk of shocks in patients with implantable cardioverter defibrillators: results from the Triggers Of Ventricular Arrhythmias (TOVA) study. Circulation 2004;109:1386 –91. 8. Desai AD, Burke MC, Hong TE, et al. Predictors of appropriate defibrillator therapy among patients with an implantable defibrillator that delivers cardiac resynchronization therapy. J Cardiovasc Electrophysiol 2006;17:486 –90. 9. Klein G, Lissel C, Fuchs AC, et al. Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study. Europace 2006;8: 618 –24. 10. Pedersen SS, van den Broek KC. ICD shocks and their adverse impact on patient-centered outcomes: fact or fiction? J Am Coll Cardiol 2008;52:1037– 8. 11. Bilge AK, Ozben B, Demircan S, Cinar M, Yilmaz E, Adalet K. Depression and anxiety status of patients with implantable cardioverter defibrillator and precipitating factors. Pacing Clin Electrophysiol 2006;29:619 –26. 12. Pedersen SS, Theuns DA, Erdman RA, Jordaens L. Clustering of device-related concerns and Type D personality predicts increased distress in ICD patients independent of shocks. Pacing Clin Electrophysiol 2008;31:20 –7. 13. van den Broek KC, Nyklicek I, van der Voort PH, Alings M, Denollet J. Shocks, personality, and anxiety in patients with an implantable defibrillator. Pacing Clin Electrophysiol 2008;31:850 –7. 14. van den Broek KC, Nyklicek I, Denollet J. Anxiety predicts poor perceived health in patients with an implantable defibrillator. Psychosomatics 2009. In press. 15. Dougherty CM. Psychological reactions and family adjustment in shock versus no shock groups after implantation of internal cardioverter defibrillator. Heart Lung 1995;24:281–91. 16. Schron EB, Exner DV, Yao Q, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation 2002;105:589 –94. 17. Pedersen SS, Theuns DA, Muskens-Heemskerk A, Erdman RA, Jordaens L. Type D personality but not implantable cardioverterdefibrillator indication is associated with impaired health-related quality of life 3 months post-implantation. Europace 2007;9:675– 80. 18. Crossmann A, Pauli P, Dengler W, Kuhlkamp V, Wiedemann G. Stability and cause of anxiety in patients with an implantable cardioverter-defibrillator: a longitudinal two-year follow-up. Heart Lung 2007;36:87–95. 19. Pedersen SS, van Domburg RT, Theuns DA, Jordaens L, Erdman RA. Concerns about the implantable cardioverter defibrillator: a determinant of anxiety and depressive symptoms independent of experienced shocks. Am Heart J 2005;149:664 –9. 20. Whang W, Albert CM, Sears SF Jr., et al. Depression as a predictor for appropriate shocks among patients with implantable cardioverterdefibrillators: results from the Triggers of Ventricular Arrhythmias (TOVA) study. J Am Coll Cardiol 2005;45:1090 –5.

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7 21. Dunbar SB, Kimble LP, Jenkins LS, et al. Association of mood disturbance and arrhythmia events in patients after cardioverter defibrillator implantation. Depress Anxiety 1999;9:163– 8. 22. Lampert R, Joska T, Burg MM, Batsford WP, McPherson CA, Jain D. Emotional and physical precipitants of ventricular arrhythmia. Circulation 2002;106:1800 –5. 23. Burg MM, Lampert R, Joska T, Batsford W, Jain D. Psychological traits and emotion-triggering of ICD shock-terminated arrhythmias. Psychosom Med 2004;66:898 –902. 24. Denollet J, Pedersen SS. Anger, depression, and anxiety in cardiac patients: the complexity of individual differences in psychological risk. J Am Coll Cardiol 2009;53:947–9. 25. Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005;45:637–51. 26. Denollet J. Biobehavioral research on coronary heart disease: where is the person? J Behav Med 1993;16:115– 41. 27. Pedersen SS, Denollet J, van Gestel YR, Serruys PW, van Domburg RT. Clustering of psychosocial risk factors enhances the risk of depressive symptoms 12-months post percutaneous coronary intervention. Eur J Cardiovasc Prev Rehabil 2008;15:203–9. 28. Beck AT, Steer RA. Manual for the Revised Beck Depression Inventory. San Antonio, TX: Psychological Corporation, 1993. 29. Strik JJ, Honig A, Lousberg R, Denollet J. Sensitivity and specificity of observer and self-report questionnaires in major and minor depression following myocardial infarction. Psychosomatics 2001;42:423– 8. 30. Van der Ploeg HM, Defares PB, Spielberger CD. Manual for the ZBV. A Dutch-Language Adaptation of the Spielberger State-Trait Anxiety Inventory [in Dutch]. Lisse, the Netherlands: Swets & Zeitlinger, B.V., 1980. 31. Kamphuis HC, de Leeuw JR, Derksen R, Hauer RN, Winnubst JA. Implantable cardioverter defibrillator recipients: quality of life in recipients with and without ICD shock delivery: a prospective study. Europace 2003;5:381–9. 32. Denollet J. DS14: standard assessment of negative affectivity, social inhibition, and type D personality. Psychosom Med 2005;67:89 –97. 33. Emons WH, Meijer RR, Denollet J. Negative affectivity and social inhibition in cardiovascular disease: evaluating type D personality and its assessment using item response theory. J Psychosom Res 2007;63: 27–39. 34. Martens EJ, Kupper N, Pedersen SS, Aquarius AE, Denollet J. Type D personality is a stable taxonomy in post-MI patients over an 18-month period. J Psychosom Res 2007;63:545–50. 35. De Jonge P, Denollet J, Van Melle JP, et al. Associations of type D personality and depression with somatic health in myocardial infarction patients. J Psychosom Res 2007;63:477– 82. 36. Denollet J, Vaes J, Brutsaert DL. Inadequate response to treatment in coronary heart disease: adverse effects of type D personality and younger age on 5-year prognosis and quality of life. Circulation 2000;102:630 –5. 37. Pedersen SS, Lemos PA, van Vooren PR, et al. Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation: a Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry substudy. J Am Coll Cardiol 2004;44:997–1001. 38. Denollet J, Sys SU, Stroobant N, Rombouts H, Gillebert TC, Brutsaert DL. Personality as independent predictor of long-term mortality in patients with coronary heart disease. Lancet 1996;347: 417–21. 39. Denollet J, Brutsaert DL. Personality, disease severity, and the risk of long-term cardiac events in patients with a decreased ejection fraction after myocardial infarction. Circulation 1998;97:167–73. 40. Pedersen SS, Denollet J. Is type D personality here to stay? Emerging evidence across cardiovascular disease patient groups. Curr Cardiol Rev 2006;2:205–13. 41. Field A. Discovering Statistics Using SPSS. 2nd edition. London: SAGE Publications, 2005. 42. Denollet J, Martens EJ, Nyklicek I, Conraads VM, de Gelder B. Clinical events in coronary patients who report low distress: adverse effect of repressive coping. Health Psychol 2008;27:302– 8. 43. Denollet J, Strik JJ, Lousberg R, Honig A. Recognizing increased risk of depressive comorbidity after myocardial infarction: looking for 4 symptoms of anxiety-depression. Psychother Psychosom 2006;75:346 –52.

JACC Vol. 54, No. 6, 2009 August 4, 2009:531–7 44. Denollet J, Pedersen SS, Ong AT, Erdman RA, Serruys PW, van Domburg RT. Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era. Eur Heart J 2006;27:171–7. 45. Denollet J. Type D personality. A potential risk factor refined. J Psychosom Res 2000;49:255– 66. 46. Pedersen SS, Denollet J, Spindler H, et al. Anxiety enhances the detrimental effect of depressive symptoms on health status following percutaneous coronary intervention. J Psychosom Res 2006;61:783–9. 47. Ladwig KH, Baumert J, Marten-Mittag B, Kolb C, Zrenner B, Schmitt C. Posttraumatic stress symptoms and predicted mortality in patients with implantable cardioverter-defibrillators: results from the prospective living with an implanted cardioverter-defibrillator study. Arch Gen Psychiatry 2008;65:1324 –30. 48. Anderson KP. Sympathetic nervous system activity and ventricular tachyarrhythmias: recent advances. Ann Noninvasive Electrocardiol 2003;8:75– 89. 49. Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990;82: I103–13. 50. Kop WJ, Krantz DS, Nearing BD, et al. Effects of acute mental stress and exercise on T-wave alternans in patients with implantable cardioverter defibrillators and controls. Circulation 2004;109:1864 –9. 51. Gold MR, Bloomfield DM, Anderson KP, et al. A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification. J Am Coll Cardiol 2000;36:2247–53. 52. Lampert R, Jain D, Burg MM, Batsford WP, McPherson CA. Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation 2000;101:158 – 64.

van den Broek et al. Anxiety, Personality, and Ventricular Arrhythmia

537

53. Sweeney MO, Wathen MS, Volosin K, et al. Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation 2005;111:2898 –905. 54. Hreybe H, Saba S. A clinical risk score to predict the time to first appropriate device therapy in recipients of implantable cardioverter defibrillators. Pacing Clin Electrophysiol 2007;30:385–9. 55. Watkins LL, Blumenthal JA, Davidson JR, Babyak MA, McCants CB Jr., Sketch MH Jr. Phobic anxiety, depression, and risk of ventricular arrhythmias in patients with coronary heart disease. Psychosom Med 2006;68:651– 6. 56. McMurray J, Kober L, Robertson M, et al. Antiarrhythmic effect of carvedilol after acute myocardial infarction: results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial. J Am Coll Cardiol 2005;45:525–30. 57. Ladwig KH, Deisenhofer I, Simon H, Schmitt C, Baumert JJ. Characteristics associated with low treatment satisfaction in patients with implanted cardioverter defibrillators: results from the LICAD study. Pacing Clin Electrophysiol 2005;28:506 –13. 58. Baumert J, Schmitt C, Ladwig KH. Psychophysiologic and affective parameters associated with pain intensity of cardiac cardioverter defibrillator shock discharges. Psychosom Med 2006;68:591–7. 59. Pedersen SS, van den Broek KC, Sears SE Jr. Psychological intervention following implantation of an implantable defibrillator: a review and future recommendations. Pacing Clin Electrophysiol 2007;30: 1546 –54. Key Words: implantable defibrillator y ventricular arrhythmias y depression y anxiety y Type D personality.