Psychological treatments in cardiac rehabilitation

Journal of Psychosomatic Research 48 (2000) 443–454

Review

Psychological treatments in cardiac rehabilitation: review of rationales and outcomes Wolfgang Linden* Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, BC V6T 1Z4, Canada

Abstract Objective: In this review, the place of psychological interventions in cardiac rehabilitation and differences in underlying rationales are presented. Treatment approaches vary in that some practitioners favor biobehavioral approaches with strong relaxation/breathing components, whereas others offer unstructured support, psychoeducation to maximize compliance, or psychological interventions directed at reducing emotional distress. Methods: The effectiveness of psychosocial rehabilitation for endpoints like mortality, recurrence, emotional distress, and intermediate hard endpoints is reviewed by integrat-

ing conclusions from narrative and meta-analytic reviews as well as recent major clinical trials. Results: The aggregated findings support the use of psychosocial interventions and they also help to explain critical differences in outcome in that studies which fail to reduce distress also fail to lead to reduced mortality or reduced event recurrence. Conclusion: Gender differences in outcome and recent trends in cardiology are discussed because both have distinct consequences for the effective delivery of psychological services to cardiac patients.  2000 Elsevier Science Inc. All rights reserved.

Keywords: Cardiac rehabilitation; Emotional distress; Therapy outcome

Rationales Introduction This review article focuses on psychosocial interventions offered to cardiac patients in support of their rehabilitation. For many health care providers, cardiac rehabilitation is synonymous with exercise-based rehabilitation and this is likely due to the fact that, in attempts to maximize the gains achieved with surgery and drug regimens, exercise rehabilitation was typically the first component added to standard medical care. More recently, cardiac rehabilitation programs have added comprehensive dietary education and psychosocial support [1,2]. Most published evaluations of cardiac rehabilitation effectively describe the outcomes of multicomponent programs, and the evaluation of individual component outcomes is essentially impossible with these protocols. The purpose of this review, therefore, is to focus on psychological interventions and on the added benefit that they can provide. The reader interested in a broader review of cardiac rehabilitation is referred elsewhere [1].

* Corresponding author. Tel.: 604-822-4156; fax: 602-822-6923. E-mail address: [email protected] (W. Linden)

Modes and targets for intervention Obviously, heart disease is not a primary psychological pathology, although psychological factors play an important role in the recovery from a major cardiac event and may, in fact, have contributed to it in the first place. The rehabilitation process varies greatly from one patient to another [3], and this is accentuated by differences in severity of underlying disease and type of medical intervention received. A first myocardial infarction hits many patients unprepared, whereas bypass surgery and angioplasty is often the result of a more lengthy chain of medical investigation, giving the patient time to prepare. Given that the psychological contributing factors and psychological reactions to cardiac disease differ from one patient to the next, there is the question of whether or not standardized treatment makes clinical sense and whether or not it can be cost-efficient. Service provider characteristics may also need to be considered insofar as the theoretical leanings and specific training of psychologists and other psychosocial clinicians have a great shaping influence on the nature of the offered interventions.

0022-3999/00/$ – see front matter  2000 Elsevier Science Inc. All rights reserved. PII: S0022-3999(99)00094-X

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The issue of individualized versus standardized treatments is of crucial importance in considering the clinical practice implications of research results as they are discussed in this article. Controlled treatment studies overwhelmingly use standardized treatments for reasons of methodological purity. Although laudable in many ways, this approach does ignore evidence that individually tailored treatment is more powerful than standardized treatment [4] and may lead to an artificial suppression of otherwise obtainable treatment benefits if patients had been treated according to identified need. In light of the foregoing it is clear that any attempt to draw firm conclusions about whether or not psychological interventions work will be handicapped by the fact that there is no single definition for what an appropriate psychological intervention is (or should be), nor is there a clear consensus as to who should be receiving this treatment. Additional variations possibly affecting outcomes are: (a) type of service providers; (b) whether treatment is group-based or individual; (c) how much treatment is available; (d) when treatment is initiated; and (e) whether treatment targets are individualized. Whereas most psychological cardiac care is provided on an out-patient basis, there is evidence that a similarly effective service can be provided using a relatively compressed, in-patient format [5]. Nonspecific treatment benefits require study as well because a certain amount of distress reduction is likely to arise from good cardiology care provided by an understanding physician who provides the relevant information, checks on the patient’s knowledge and corrects it when necessary, and provides stable care [6]. Another issue is the ethics of certain research protocols: when a multicomponent treatment package has been offered and found beneficial, serious ethical issues arise when, later on, researchers want to use a treatment-dismantling strategy to uncover the specific contributions of each treatment component. Rationale for intervention Different clinical research groups have developed quite diverse rationales and protocols for their interventions, but careful reading of the available research suggests that this diversity is mostly a reflection of the true complexity of underlying risk factor models rather than a lack of thought on the part of researchers and clinicians. The work of four behavioral research groups has dominated the cardiac rehabilitation landscape and the differences in their approach serves to illustrate the possible variety of interventions: Ornish et al. [7,8]; the Recurrent Coronary Prevention Project (RCPP) [9]; the IHDLSM study group [10,11]; and Van Dixhoorn [16–19]. I attribute the “dominance” of these four approaches to the good design quality of the originating studies; their sheer size (particularly for the RCPP and IHDLSM); the dem-

onstration of reversible risk via reductions in artery occlusion [7] (shown in Ornish’s work); and the demonstration that even a brief, relatively nonspecific, inexpensive psychosocial intervention can nevertheless lead to substantial reductions in mortality and cardiac event recurrences [10,11]. How can the different approaches to psychosocial cardiac rehabilitation be classified and differentiated? Blumenthal and Emery [12] suggested that interventions are: (a) either behavioral interventions for risk behavior reduction (weight loss, smoking cessation, nutrition, improved exercise adherence); or (b) more generically directed at reducing psychological distress. Intervention may again be a quite heterogeneous group of treatments encompassing relaxation strategies; more complex stress management approaches including behavioral change and cognitive retraining; reduction of type A behavior; treatment of depression, anxiety, and panic; or any combination of these various methods. The pioneering research groups were systematically different in the kinds of intervention they offered and tested, and their inherent diversity has pushed the field into multiple research directions. Ornish To the population at large, Dean Ornish may well be the best known medical expert on comprehensive cardiac rehabilitation. He has been very effective at marketing his approach via standard scientific channels like journals and conference presentations but also through popular book sales [13]. In 1983, Ornish and colleagues published a landmark study in JAMA [7]. Forty-six well-defined heart disease patients had been randomly assigned to a control group (receiving standard cardiologic care while living at home) or an experimental group. The experimental group was subjected to a rigorous 3.5-week program while being housed together in a rural environment. The latter group was served a strict vegetarian, low-fat diet of 1400 kilocalories per day and was taught hearthealthy food purchasing and preparation habits. They also learned and practiced meditation and relaxation for 5 hours per day. Experimental patients relative to controls demonstrated a 44% mean increase in duration of exercise, a 55% increase in total work performed on an exercycle, and other signs of improved cardiac function. Furthermore, cholesterol decreased by 20.5% and angina episodes were reduced by 91%. Given this “package” approach it was not possible to determine whether the observed changes were attributable to stress management or to the nutrition intervention. In a subsequent study, Ornish’s group [8] repeated the basic treatment protocol, but also added angiographic measures so as to document changes in atherosclerosis severity. Twenty-eight patients were assigned to the treatment package and 20 to a usual-care control

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group. In the treated group, the average percentage diameter stenosis regressed by 15.5% (i.e., patients improved), whereas it worsened by 15% in the control group. These results are particularly intriguing because they suggest that lifestyle change has a direct effect on the underlying disease by reducing the narrowing of arteries. In a further breakdown of these results, these investigators also showed occlusion reversal but only among those with high compliance to the nutrition and exercise recommendations, suggesting a gradient effect of lifestyle change on vessel occlusion. Critiques of the Ornish approach have been plentiful. Although the strength of his approach was to show that lifestyle changes can also reverse atherosclerosis, it was also that true patients with low or even moderate degrees of compliance showed no atherosclerosis reversal. Full compliance meant dramatic changes in lifestyle (nutrition, exercise, and handling of stress), often involving support and collaboration of spouses. Clinicians have charged that few patients are willing to subject themselves to such drastic changes, and even though this does not speak against the Ornish approach per se, it implies that this drastic approach is not likely to be adopted by the majority of patients. The required level of motivation and persistence may apply only to a select, small group of patients and affordability of such a comprehensive intervention may be yet another limiting factor for mass implementation. Recurrent Coronary Prevention Project (RCPP) A particularly large and highly influential trial of behavioral risk factor reduction in cardiac patients is the RCPP [9]. The premise of this trial was that type A behavior and other behavioral risk factors (i.e., nutrition, alcohol use, and exercise) required aggressive intervention. A control group of 270 patients was followed in parallel with the treatment groups, but it is important to note that the controls had not been randomized into the control condition. The treated group was again subdivided and randomized into either cardiac counseling (CC) (20 sessions) or CC plus intensive type A behavior counseling (for a total of 43 sessions). All interventions were provided in group format. CC consisted mostly of education about medication regimens, diet, and exercise, with occasional consultation on anxiety, depression, and phobias. The CC plus type A treatment also included detailed instruction in relaxation methods, recognition of stress symptoms, and modification of stressproducing cognitions. Follow-up has now been extended up to 6.5 years and, in constrast to the IHDLSM, the benefits obtained were more stable over the long followup. Specifically, mortality in the CC plus type A treatment was about half of that in the control group, and the CC group results fell in between. Cardiac event recurrence was reduced as well with the active treatments. Type A behavior itself was notably reduced and

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this change was considered instrumental for the benefits in mortality and morbidity. The results from this study suggest that treatment effects may be proportional to the amount of intervention, which — given the group format — was still relatively inexpensive even for the groups having 43 sessions. The Ischemic Heart Disease Life Stress Monitoring Program (IHDLSM) The IHDLSM [10] differs from the great majority of cardiac rehabilitation studies in that patients were randomly assigned to either a control group (N ⫽ 224) or a “stress monitoring” condition in which nurses provided nonspecific psychosocial support (N ⫽ 229). These nurses were not trained specifically as psychotherapists and responded to patients on an as-needed basis. More specifically, patients were contacted on a monthly basis and stress was assessed on each occasion using a brief standardized tool. Only when stress was elevated did the nurse provide intervention. This approach reflects best what actually happens in clinical practice; however, it also fails to allow an assessment of which intervention component had what effect. The patients from this study have now been followed for 6.5 years. At 1-year follow-up, treated patients had only about half the mortality rate of the untreated ones, but long-term follow-up indicated a gradual but steady decline of these treatment benefits. Interestingly, Frasure-Smith [14] later reanalyzed her data and grouped patients into two subgroups: those scoring ⬎5 on the General Health Questionnaire (GHQ), completed while still in hospital, were labeled “high stress,” and the others were labeled “low stress.” At 5-year follow-up, it was quite apparent that the low stress group did not benefit from intervention in that their mortality rates were relatively low anyway, and indistinguishable from the control group subjects with low stress. Treated high-stress patients, however, showed only about one third the mortality rate over 5 years postevent than did their untreated, high-stress counterparts, suggesting that random assignment of all cardiac patients to psychological treatment without an assessment of actual psychological need may not be cost-efficient. Unfortunately, Frasure-Smith et al. [15] showed rather disappointing results in a recent replication of the IHDLSM study. This time the sample was even larger, included women, and was somewhat older on average (essentially due to the inclusion of female heart patients who tend to be older). The intervention was the same as in the first study. There was no treatment benefit for survival among men (2.4% vs. 2.5% over 12 months), but there were higher mortality rates for treated women (10.3% vs. 5.4%). The intervention led to only minimal reductions in anxiety and depression.

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These conflicting results, their meaning, and their implications for clinical practice are discussed later in this article when meta-analytic findings are compared. Van Dixhoorn Van Dixhoorn’s approach [16–19] focuses on general arousal reduction via breathing training. This approach is based on a psychophysiological rationale suggesting that sudden cardiac death may be triggered by unstable autonomic system activity. Specifically, this model posits that increased sympathetic arousal as well as decreased vagal control may destabilize cardiac rhythms. Support for the usefulness of breathing methods can be derived from Sakakibara’s work [20,21]. In one study, Sakakibara et al. [20] tested college students with ECGs and pneumograms during 3 ⫻ 5 min practice of autogenic training (AT; a relaxation method with a strong breathing component [22]) or the same length of quiet rest (a nonspecific control condition). Analysis of respiration and heart rate variability data suggested that the AT practice was associated with enhanced cardiac parasympathetic tone, whereas the quiet rest period was not. This suggests that arousal reduction via AT may be attributed at least in part to enhanced parasympathtic activity. Later, Sakakibara and Hayano [21] showed that the practice of slow respiration prevents vagal withdrawal during threat. Although the emphasis on heart rate variability is relatively novel, there is further support for its importance as Horsten et al. [23] showed that social isolation and inability to relieve anger were associated with decreased heart rate variability even in currently healthy women. Treatment of depression Depression is now considered a major prognostic factor for poor outcome in cardiac patients. However, the strength of this is based largely on studies published in the last decade and, not surprisingly, there has been little research so far on the cardiac outcome of depression screening and treatment in these patients. Most relevant appears to be an ongoing study by Freedland et al. [24], from which first pilot outcome data were made public in 1996. They reported on a trial with depressed cardiac patients who received cognitive-behavioral therapy (with an average of nine sessions). Twenty-three patients were evaluated: their scores on the Beck Depression Inventory were reduced from 19.0 to 11.8 after therapy (note that a score of 10 is taken to represent the cutoff between mild depression and no depression). This area of research has already generated much interest and is likely to trigger a wave of treatment studies. Particularly noteworthy in this context is a large, multisite study currently under way in the USA, the ENRICHD trial. In this study, patients are selected for high levels of depression and/or lack of social support. Depression will be treated with a manualized cognitive

therapy approach that is widely tested, but it has not been elucidated how the social support intervention proceeds [25]. Results may be available in the year 2000 and are eagerly awaited given the size and importance of this trial. Coronary-prone personality The existence of a coronary-prone personality was operationalized as type A behavior and has evolved to focus on hostility as the other components of Type A behavior did not appear to have much predictive validity for cardiac mortality. Although type A behavior reduction has been a focus in the RCPP trial [9], there is less evidence that shows cardiac benefits are likely if hostility is specifically targeted in psychotherapy and this is an area worthy of further study. A different coronaryprone behavioral style, referred to as type D, has been proposed by Denollet, consisting of two components: a defensive personality style paired with high negative affectivity (i.e., emotional distress). Denollet has convincingly shown that the presence of this style predicts mortality after cardiac infarction with a 5:1 odds ratio [26,27]. Given the recency of this development, it remains to be determined which psychological interventions may be effective in changing type D behavior and whether or not previous success with mortality and morbidity reductions can be attributed, at least in part, to change in type D behavior. Choice of outcome variables in cardiac rehabilitation It is questionable whether exclusive targeting of mortality reduction makes sense for patients themselves or for insurance companies and health care plans [28]. Even if treatment could extend life expectancy by a number of years, little of value may be achieved when patients survive a heart attack or other cardiac event only to remain handicapped, distressed, and with a high likelihood of frequent cardiac event recurrences, need for rehospitalization, and multiple surgeries. Arguably, a better possible outcome is sudden death after many years of life in a relatively disease-free state characterized by a high quality of life. If extending life can only be “purchased” by spending this time in a chronically debilitated, uncertain, and distressing state, then individual patients (if given a choice) might not want such treatment. This is already true in the treatment of cancer where end-stage cancer patients often refuse to undergo more aggressive treatments because of their powerful side effects. Hence, an improvement in quality of life and reduction in cardiac event recurrence may be more “worthy” outcomes than mortality reduction itself, and this perception may actually be shared by patients and their insurance carriers. A catchy phrase describing this phenomenon states that we should not necessarily push to “add years to life” but rather “add life to years” instead. Thus, to “add life to years” means to target

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depression and anxiety, help patients to become active and guardedly optimistic, and to try to reduce behavioral risk factors and thus prevent recurrence. Outcomes There have been many published reviews of the outcome of cardiac rehabilitation programs and rereviewing all of them in detail would be redundant. Analyzing these reviews, however, has revealed some interesting and meaningful trends over time. The early reviews were typically narrative in nature; later on, statistical meta-analyses were added to the literature and, as will be shown in what follows, they contributed greatly to solidifying conclusions and recommendations. Narrative reviews Narrative reviews became increasingly more positive over time in their judgment about the efficacy of psychosocial interventions. Razin [29] was cautiously optimistic that psychosocial treatment may be useful, and cites mostly clinical lore and little controlled research in support of this conclusion. Hill et al. [30] more firmly state that psychological treatment reduces distress, but they also urge researchers to study other, nonsubjective endpoints. Blumenthal and Emery [12] also concluded that psychological distress can be reduced in cardiac patients, but they were not convinced by the data on mortality reduction. Five years later, another review by Blumenthal and Wei [31] closed with a notably more positive evaluation of the impact of psychosocial treatment. Throughout these reviews, there was an apparent difficulty in generating strong messages for clinical practice because of the great diversity in treatment content, length, and choice of behavioral targets. It is for this reason that the different approach of statistical metaanalysis has been able to shed some further light on the issue of effectiveness. Meta-analytic reviews Efficacy reviews of psychological cardiac rehabilitation can be subdivided into those that are preventive in nature (i.e., targeting those at risk for heart disease) versus those in which patients clearly have diagnosed heart disease. The one available meta-analysis on psychosocial interventions for the primary and secondary prevention of CAD exclusively focused on the modifiability of type A behavior and its associated health benefits [32]. Seven of the 18 studies reviewed by Nunes et al. [32] represented samples with documented CAD, whereas the others were samples of healthy individuals. Not surprisingly, Nunes et al. found that the size of effect went up with more intensive intervention. The effect of psychosocial treatment relative to controls (typically on medication) was evaluated for mortality and morbidity at 1- and 3-year follow-up. For the 1-year

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follow-up, the effect size was d ⫽ 0.34 for mortality reduction (not significant), d ⫽ 0.45 for recurrent myocardial infarction (MI) reduction (significant at p ⬍ 0.05), and d ⫽ 0.57 for combined MI recurrence and mortality (significant at p ⬍ 0.05). For the 3-year followup, only the combined mortality and morbidity figures suggested further enhancement of the clinical benefit with d ⫽ 0.97 (significant at p ⬍ 0.001). Note that, at the time of the Nunes et al. review, researchers had not yet differentiated operational definitions of a type A behavior pattern from later demonstrations of hostility as the most toxic component of type A behavior. It is therefore possible that specifically targeted reductions in hostility could also produce more benefit than possible when all components of the type A behavior pattern are targeted. This possibility requires further investigation. To have a good basis of comparison for the discussion of treatment effects due to behavioral interventions, a summary of a pivotal review by Lau et al. [33] on medical and nonmedical treatments may be helpful. Lau et al. reported a cumulative meta-analysis of major, controlled interventions for coronary artery disease (also referred to as secondary prevention) using mortality as the clinical endpoint. The cumulative odds ratios for all secondary prevention efforts indicated that the three most useful interventions were anticoagulants, rehabilitation regimens, and ␤-blockers, each accounting for approximately 20% reduction in mortality. Treatmentspecific mortality reductions of 20% are clinically significant and this figure may be considered the “gold standard” for judging the efficacy of other interventions. In one meta-analysis of behavorial interventions, Oldridge et al. [34] specifically targeted exercise and risk factor rehabilitation in their meta-analysis of ten randomized clinical trials. These ten trials were carefully screened to include only studies with a high-quality methodology and included 2145 control patients and 2202 rehabilitation patients. The pooled odds ratios suggested a 24% reduction in all-cause deaths and a 25% reduction in cardiovascular deaths for the rehabilitation groups relative to the control groups on standard medical care. Although exercise was associated with a reduction in incidence of death, it did not have an impact on recurrence. From a quality-of-life and a health insurance point of view this is a disappointing finding because reduced recurrences are very important to individuals’ courses of disease. Oldridge et al. [34] further tested whether predominant emphasis on exercise or emphasis on behavioral risk factor reduction made a difference, whether treatment length affected long-term outcome, and whether time of rehabilitation initiation was associated with differential benefits. Studies were classified as being mostly exercise rehabilitation with some risk factor counseling, or mostly risk factor counseling with some exercise recommendations. Even with these differ-

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ent emphases, the treatments were found to be equally beneficial. The design of this meta-analysis did not allow the investigators to fully distinguish the unique effects of exercise rehabilitation from the unique effects of risk factor counseling. Longer treatment led to greater mortality reductions but only in those studies in which follow-up lasted ⬎3 years. The timing of the intervention (grouped into ⬍8 weeks postevent and ⬎8 weeks postevent) had only negligible impact on outcome. One meta-analysis of the associated psychological benefits of exercise treatment nicely complemented the Oldridge et al. review. Kugler and coworkers [35] identified 15 studies of exercise rehabilitation that also monitored psychological changes in patients undergoing an exercise program. These researchers reported that exercise alone without any specific attempt at psychological intervention produced significant reductions in anxiety (effect size d ⫽ ⫺0.31) and depression (d ⫽ ⫺0.46). Ketterer [36] conducted another meta-analysis of the effectiveness of behavioral interventions and included data from eight randomized, controlled clinical trials. His findings indicated that behavioral interventions relative to controls accounted for a 39% reduction in subsequent nonfatal MIs and a 33% reduction in cardiac deaths. These risk reduction factors were based on follow-ups of varying lengths ranging from 0.5 to 7 years. Similar to previous analyses, the specific contribution of various treatment components were not clearly extricable. The Oldridge et al. [34], Ketterer [36], and the Lau et al. [33] meta-analyses concurred in the observed benefit associated with nondrug approaches to cardiac rehabilitation and support its routine inclusion in cardiac care. Nevertheless, in the wake of these studies, there remained a lack of clarity about the specific effect that psychological interventions might have relative to nutrition and exercise interventions. Our own research group attempted to fill this gap in knowledge [38]. We performed a statistical meta-analysis of 23 randomized, controlled trials that evaluated the additional impact of psychosocial treatment for rehabilitation from documented coronary artery disease. Anxiety and depression measures were pooled into an index of psychological distress because they correlate closely and appear to tap the same underlying psychological dimension. Other clinical endpoints studied were biological risk factors, mortality, and recurrence of cardiac events. Mortality data were available from 12 and recurrence data from 10 of the 23 studies. The stringent application of a fullrandomization principle as an inclusion criterion would have precluded analysis of the Recurrent Coronary Prevention Project (RCPP) [9]. In the RCPP, patients were randomized into the two available active psychosocial treatment conditions, but the “standard treatment controls” had not been randomized into their condition

largely due to ethical reasons [39]. Complete exclusion of the data from this study would have been unfortunate, because it was the largest study completed at that time. To maintain a full randomization inclusion criterion (and derive scientifically sound conclusions) while still considering the results from the RCPP, it was decided to conduct all analyses first without RCPP data, and then repeat the analyses including the RCPP data. Follow-up data were clustered into short (⬍2 years) follow-up, and long follow-up (⬎2 years) to allow testing of long-term benefits of interventions. The longest follow-ups included in this analysis were 8 and 5 years, respectively. The average length of follow-up in the ⬍2 years category was 12 months; the average length of follow-up in the ⬍2 years category was 63 months (5.2 years). The results were quite consistent with those of previous reviews, both narrative and meta-analytic. The observed odds ratio reflected a 46% reduction in recurrence for the ⬍2-year follow-up and a 39% reduction for the longer follow-up. The observed benefit for the ⬍2-year follow-up was equally true for comparisons including and excluding the RCPP data. Analyses of the tests of psychosocial treatment on mortality (using fully randomized trial data only) revealed treatmentrelated mortality reductions of 41%. For follow-up ⬎2 years, there was a continuing trend for mortality benefits (26%), but this was not statistically significant. When the RCPP [9] data were included in the analyses, the mortality reduction results of ⬍2-year follow-up were essentially the same at 43%. Inclusion of the RCPP data for the longer term follow-up improved the observed benefit of psychosocial treatment on mortality rates; that is, a 28% reduction was observed. The benefits of psychosocial treatment for reduced recurrence of cardiac events were very similar in magnitude and mapped onto the reductions in mortality. With respect to psychological distress and biological risk factors, patients in the control conditions changed very little (compared with pretest), and—if anything— they got worse. Psychosocial intervention, on the other hand, was associated with reductions in psychological distress (d ⫽ ⫺0.34), heart rate (d ⫽ ⫺0.38), cholesterol (d ⫽ ⫺1.54), and systolic blood pressure (d ⫽ ⫺0.24). Impact of recent studies on conclusions available from meta-analyses The reviews just described presented a rather positive set of conclusions about the impact of psychosocial treatments for cardiac patients. Interestingly, since the publication of the review by Linden et al. [38], three large-scale studies have been completed and published. Together, they present a rather “mixed bag” of optimistic and pessimistic conclusions. Jones and West [40] reported the results from a very large trial in which additional psychological intervention

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was contrasted with standard care in a sample of 2328 post-MI patients. A multicomponent stress management rehabilitation program had no apparent additional benefit for mortality, clinical complications, anxiety, or depression. Treated patients did report less angina and less medication usage. It is noted that the researchers randomized all patients into one of the two treatment conditions, irrespective of whether or not elevated stress, anxiety, or depression were present. Curiously, Jones and West also reported that all patients suffering from MI in the six participating hospitals were randomized, thus indicating that the reported refusal rate was zero. Also of importance is the fact that the mortality rate for both groups was only 6% over the following 12 months, thus making it difficult to distinguish experimental from control treatment due to low base rates. Another very large, recent trial with disappointing results was the one conducted by Frasure-Smith et al. [15], described earlier. Given the large size and good controls associated with these studies, their addition to the Linden et al. [38] meta-analysis would certainly have reduced the observed mortality and recurrence benefits. Frasure-Smith et al. [15] provided a number of viable hypotheses for these seemingly contradictory findings and I will add another one here. First, relative to clinical studies conducted some 15–20 years ago, the quality of “standard” cardiac care has improved so that mortality rates in standard care treatment control groups are only a fraction of what they used to be. This means that “proving” small-to-moderate psychological treatment benefits on mortality outcomes would require tens of thousands of patients to be followed over many years. The cost would be enormous. A second important feature in the Jones and West [40] study is that most of the patients enrolled were neither anxious nor depressed and showed very little subsequent change on these variables. The overall rationale of offering psychological interventions to cardiac patients is, of course, to reduce psychological distress when present, and it is this targeted change that is commonly believed to account for improved cardiac health in treated patients. At the very least, the Jones and West [40] study suffered from a floor effect in that many patients had little need for treatment and, correspondingly, little room for improvement; the same may also be true, although to a lesser degree, for the FrasureSmith et al. replication study [15]. This point comes particularly clear in a new meta-analysis [41] in which a somewhat larger sample of studies (N ⫽ 37) was available for analysis and these included the replicated Frasure-Smith et al. and West and Jones trials with their very large samples and null findings, respectively. Dusseldorp and colleagues [41] compared standard care with additional psychological treatment (as was done by Linden et al.) and noted reductions in mortality odds for psychological treatment that ranged from 6% to

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52%, depending on the length of studied outcomes. Psychological treatment had no positive impact on short-term MI recurrence (⫺16%), but still showed 41% reductions in medium and long-term follow-ups. Most striking was a comparison of outcomes for those studies in which psychological treatment failed to produce psychological changes with those in which it succeeded. When psychological distress was not reduced by treatment, patient mortality was higher than that of controls (odds ratio 0.88:1) and MI recurrence was not affected (odds ratio 1.03:1); however, when psychological distress was reduced, the odds ratio for mortality was 1.52:1 and for MI recurrence was 1.69:1. Finally, it needs to be noted that the earlier studies tended to offer treatment almost exclusively to men who in turn tended to be younger than the female cardiac patients who were also enrolled in the latter two studies. We must consider seriously the possibility that older patients (who more often tend to be women) benefit less from our standard treatment approaches and that treatment needs to be either specifically targeted to the psychosocial needs of older women, or that these women may be actually be better off without therapy. The latter conclusion of course sounds rather drastic and unconventional, but it does need serious consideration given the Frasure-Smith et al. [15] findings. The cardiac patient is, of course, the fortunate beneficiary of improved cardiological care and its associated lower postevent mortality rates, even if this makes it difficult to conduct further clinical trials. Researchers, as a consequence, may have no choice but to design trials with other endpoints that are likely to change over time and which are important prognostic indicators. Such endpoints can be psychological in nature (e.g., depression) or intermediary, hard cardiac endpoints like ischemia, premature ventricular contractions, or heart period variability. This latter approach has been reflected in a stress management intervention trial [42] in which outcomes were contrasted to those from an exercise control condition. The treatment was a smallgroup, cognitive-behavioral intervention lasting 16 weeks with one 1.5-hour session/week; patients were not preselected for high psychological distress. During the 38-month follow-up, the stress management group had a relative risk of only 0.26 of event recurrence in comparison to exercise controls. Ischemia was also more positively affected by stress management than by exercise. Stress management was uniquely associated with significant reductions in hostility and self-reported stress, but not with any unique advantages for reducing depression nor trait anxiety. Cost implications of the psychological treatment of cardiac patients Thorough analyses of cost–benefit evaluations are now being added to the literature [28], and suggest that

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comprehensive cardiac rehabilitation programs are economically justified. The average treatment cost per patient in the Oldridge et al. [28] study was US$790. It is also important to note that psychosocial treatment is often delivered in group format — and, at an estimated cost of $20/patient per hour, even the longest group treatment program tested so far (approximately 58 hours [11]) could be delivered for about US$1200 per patient. Although cost is relatively easy to determine, “benefit” may be defined one way by patients but defined differently by insurance carriers. Although not yet tested directly, a multistep approach with screening and identification of individual needs is the most promising from an efficiency point of view [1,43,44]. Emerging new directions in psychology and cardiology Chronic heart failure (CHF). As the field of cardiology itself changes (improved surgical technique and new, more potent medications) patients live longer. Given that better management of heart disease is not equivalent to a cure, however, good initial management also contributes to a growing number of patients who survive their first myocardial infarction or respond well to revascularization, and who ultimately move into a condition of chronic heart failure. Correspondingly, this provides new challenges for psychological supports trying to manage symptoms and maximize quality of life (QOL). Once diagnosed, CHF patients have an average life expectancy of 5 years [45], and QOL of life is generally poor because of chronic symptoms and the known poor prognosis. These patients account for a large portion of expensive emergency hospitalizations. A group of Swiss researchers analyzed the causes of such emergencies in 111 consecutive patients [46] and found that the primary cause for readmission was poor compliance with the treatment regimen (e.g., irregular use or complete refusal of medications, and excess salt and fluid intake). Other, less often cited, causes for the emergency were uncontrolled hypertension, insufficient diuretic therapy, angina, MI, and rhythm disturbances. With noncompliance being the most frequent reason, the researchers further investigated patient knowledge and found that a prime reason for nonadherence was a total or critical lack of knowledge about the purpose and necessary procedure for the medication regimen, insufficient follow-up by local physicians, and difficulties with adherence to the behavioral prescriptions. The conclusion was that thorough patient education with close follow-up was considered a highly cost-efficient means of managing these patients and of preventing repeated emergency hospitalizations. More recently, Fonarow and colleagues [47] showed that the addition of a psychoeducational component to standard medical CHF care led to improved functional status and an 85% decrease in the hospital readmission rate for the 6-month follow-up; the estimated savings for the hospital were

US$9800/patient. Furthermore, there is growing evidence that aggressive drug therapy for CHF will lessen the associated symptoms and enhance patients’ physical functioning, and, to a lesser degree, improve their subjective QOL [48]. Interestingly, the severity of the underlying disease is essentially uncorrelated with QOL, depression, or anxiety [48,49] . Accumulating research provides further good news: McKelvie et al. [45] reviewed the literature on exercise training for CHF and found that, although exercise is not likely to repair the failing heart itself, functional exercise capacity can be substantially improved with exercise training at no additional risk. Peripheral changes in skeletal muscle blood flow, metabolism, and structure may account for these improvements. Furthermore, the addition of behavioral change programs (nutrition, weight control) and psychological interventions leads to significant improvements in QOL [49–51]. Although the latter two articles provide good summaries of research, the Kostis et al. [49] investigation is a prominent example of a revealing, timely treatment study. The nonpharmacological treatment condition was added to a subsample of drug-treated patients and consisted of graduated exercise training, stress management and cognitive therapy, and dietary intervention. The additional nonpharmacological treatment was well tolerated by patients and improved exercise tolerance and reduced body weight, depression, and anxiety. Interestingly, the placebo-controlled evaluation of digoxin treatment revealed an improvement in ejection fraction, but without any corresponding change in exercise tolerance or QOL. Clearly, the “take-home” message from this work is that combined aggressive medical management, thorough patient education, and behavioral and psychological treatment form a potent intervention that has considerable promise, not only for patient benefit, but also in terms of reduced number of emergency hospitalizations and lower health care costs. Heart transplantation. A subgroup of CHF patients may have the opportunity to undergo heart transplantation and, due to more experience with the transplantation surgery itself and the necessary subsequent rejection management, success rates for heart transplantation today are quite good, with 10-year survival of about 60% [52]. Nevertheless, transplantation is a medically complex and emotionally difficult process and it poses particular challenges in the area of adherence. The transplant patient’s QOL is typically poor while waiting for surgery; psychological interventions for anxiety, depression, and overall emotional coping are needed and have been shown to be beneficial [48,53]. Both the pretransplant waiting periods and subsequent recovery require a very supportive social network. An additional, largely unavoidable stressor is the fact that transplants are done only in major hospitals, typically university teaching hospitals, and patients not liv-

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ing in the city may have to relocate at least for a few months, often isolated from their families and at considerable expense. At posttransplantation, patients need to follow a complex medication regimen consisting of immunosuppressant, cardiac, and often other medications. Also, considerable pressure is put on transplant patients to maintain an extremely healthy lifestyle: weight control and a healthy diet are crucial as is a reasonable exercise program. Return to work is a viable prospect for some but certainly not all patients, and the transplantation often triggers deep existential questions such as: How is the donor family affected? Why do I deserve this heart? What is important in my next years of life? Restenosis. Angioplasty has become a frequently used intervention largely because it is less invasive than bypass surgery. Unfortunately, 30–40% of vessels reocclude following angioplasty (i.e., restenosis), mostly within 6 months following surgery. Although severity of initial blockage and location of the vessel predict restenosis to some degree, much of the medically unexplained variance has been linked to psychological factors. In particular, the constructs of vital exhaustion and cognitive adaptation theory have been used to show the predictive power of psychological factors for explaining restenosis [54–56]. Cognitive adaptation theory captures a sense of optimism, high self-esteem, and mastery, and also predicts lower likelihood of restenosis [55], whereas vital exhaustion refers to a sense of lack of perceived energy, demoralization, and irritability, and predicts greater rates of restenosis [54]. Interestingly, Helgeson et al. [55] made no reference to the vital exhaustion literature, although cognitive adaptation sounds much like the opposite of vital exhaustion. Given that they have opposing effects on restenosis it could be that they are actually two sides of the same coin. Appels et al. [56] developed a brief cognitive-behavioral intervention and showed that this treatment program has potential in reducing restenosis rates. Conclusion Aside from the emerging arena of managing chronic heart failure, there appear to be a number of important conclusions that may guide clinicians and researchers in guiding their next steps in psychosocial cardiac rehabilitation. There also remain many open-ended, crucial questions on the research agenda. What do we know? Psychosocial interventions, when added to other active rehabilitation conditions, can improve the odds for mortality and for nonfatal MI recurrence, but this may not apply to female and older participants. Those with little emotional distress are not likely to benefit. In cases in which follow-up from randomized clinical trials was extended beyond 2 years, only three fully randomized trials provided relevant information,

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thus further limiting the generalizability of findings and weakening the power of the tests. It will be of interest to find out whether the recently completed trials with essentially null findings [15,40] will continue to show null findings when follow-up exceeds the currently available 1-year, posttreatment observation periods. The paucity of studies that reported biological risk factors is unfortunate and routine inclusion of standard risk factor measures like weight, lipids, and blood pressure is strongly suggested for controlled trials and program evaluation efforts in cardiac rehabilitation. Although “trendy,” meta-analysis is no miracle solution and its advantages need to be considered in light of its inherent flaws. One such weakness is that effects are reported as a single number (for every endpoint), thus ignoring differences in observed effects for different populations. Particular concern may arise from the fact that we have somewhat conflicting information on gender differences in treatment effectiveness. The number of available studies for this badly needed type of fine-grained meta-analysis is not sufficient and either more studies or a single, large, well-controlled trial is needed to assess the question of subgroup effects. What are the clinical implications of what we know? Psychosocial interventions deserve inclusion in cardiac rehabilitation programs in addition to drug therapy and exercise regimens. Because some interventions have failed to change psychological endpoints it is important to screen patients for actual psychological need and to demonstrate continuously that the particular intervention chosen does have an impact on psychological well-being. Observed benefits include not only targeted psychosocial endpoints like depression and anxiety but could also be demonstrated for biological risk factor reductions and, even more importantly, for improving the odds ratios for mortality and nonfatal MI and other cardiac event recurrence. The literature on risk factor reduction with behavioral interventions is still in need of further investigation, as the small number of studies using biological measures indicates. The consistency with which psychosocial treatment generalizes to different classes of endpoints is encouraging. Nevertheless, it is unlikely that all interventions have the same effect, and the particular strengths and weaknesses of various approaches need to be compared individually for a fair assessment. What do we still not know? The findings from this and previous reviews challenge researchers to pursue further resolution of the specificity question, because the relatively few and diverse studies that were presented do not allow for an unequivocal answer about why psychological interventions work. Nevertheless, it is consistent with the psychotherapy outcome literature to assume that much of the observed benefit is not specifically linked to technique, but is

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attributable to shared nonspecific therapy factors like emotional support, establishment of hope, and a sense of control [6]. Routine provision of the same lengthy psychosocial treatment programs for all post-MI patients may not be cost-efficient. More lengthy and intensive interventions consistently produce better outcomes, but more treatment is by definition also more expensive and there is strong reason to believe that the curve reflecting the relationships between increasing benefit with increasing cost ultimately levels off; at some point, more treatment may no longer add more benefit. Where this “leveling-off” point is remains to be determined. Given the apparent potential of psychosocial interventions for at least some cardiac patients, but in the absence of a clear explanation about how they work, more effort is urgently needed to identify which patient is likely to benefit most from what kind of treatment. At the clinical level, patient screening and selective assignment or referral for psychological therapy appears to be more cost-efficient than giving all patients the same amount and type of intervention. Treating clinical depression in post-MI patients appears to be a particularly urgent intervention because of the known impact of depression on poor prognosis [57]. Although it seems clinically sensible to aggressively target depression, given its associated risk for poor prognosis, there is as yet no evidence from controlled clinical trials that psychological treatment of depression improves patients’ cardiac prognosis. Psychosocial treatment, even if it is not specifically labeled as therapy for depression, reduces anxiety and depression as well as mortality and cardiac event recurrence, but the nature of this review does not safely permit the conclusion that the reduction in biological risk is the consequence of successful treatment of depression. It may be that psychosocial treatment in general, even when not specifically focusing on depression, contributes to alleviating depression and thereby affects prognosis. Whether or not screening and aggressive therapy for depression could produce greater reductions in distress than is apparent in more generic cardiac rehabilitation programs, and whether or not it causally changes cardiac prognosis, is still unknown. Answering this question is, however, timely and will have great impact on sound clinical practice. The agenda for further research on cost-efficiency and “what-outcome-for-whom” in psychological cardiac rehabilitation is a lengthy one. Without claiming to be fully comprehensive, the following questions map out a research agenda: 1. Do the different approaches to psychosocial rehabilitation described herein have similar impact on cardiac prognosis? 2. If psychotherapy is offered and effective in reducing distress, does that spill over into better adherence to other risk-reducing behaviors?

3. If behavioral risk factor reduction is aggressively pursued, does it improve quality of life and reduce distress as well? 4. Which type of psychological treatment approach is best for which type of cardiac patient? Current treatment approaches may be especially ill-suited for older female patients. 5. Is the current view of a multistep, screening, and targeted intervention program the most costefficient? In summary, it appears that, presently, a most costefficient model has the following components: training and support of all staff dealing with behavioral risk factors (nurse, nutritionist, exercise specialist, cardiologist, psychologist, social worker); routine screening of patients for psychological risk (especially depression) providing group format, standard instruction in stress management, emotion coping, and adherence; and, finally, working on a case-by-case basis with individual patients for psychotherapy in cases of extreme anxiety or depression or difficulty with smoking cessation, and adherence to exercise and nutrition guidelines.

Acknowledgments During the preparation of this article the author was financially supported by grants from the Medical Research Council, the BC and Yukon Heart and Stroke Foundation, and the Social Sciences and Humanities Research Council of Canada. Appreciation is expressed to Dr. Nancy Frasure-Smith and two anonymous reviewers who provided valuable feedback on an earlier draft of the manuscript.

References [1] NHS Centre for reviews and dissemination. Effective health care: cardiac rehabilitation. York, UK: University of York 1998:1–13. [2] Langosch W. Psychological effects of training in coronary patients: a critical review of the literature. Eur Heart J 1988; 9(suppl):37–42. [3] Taylor CB, Berra K Psychosocial factors in rehabilitation. J Cardiopul Rehabil 1993;13:78–79. [4] Paul D, Linden W, Corcoran K. Targeted and surreptitious quality of life changes in depressed and non depressed cardiac rehab participants. Psychosom Med 1999;61:106. [5] Johnston M, Foulkes J, Johnston DW, Pollard B, Gudmansdottir H. Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial. Psychosom Med 1999;61:225–233. [6] Roberts AH, Kewman DG, Mercier L, Hovell M. The power of non-specific effects in healing: implications for psychosocial and biological treatments. Clin Psychol Rev 1993;13:375–391. [7] Ornish D, Scherwitz LS, Doody RS, Kerten D, McLanahan SM, Brown SE, DePuey G, Sonnemaker R, Haynes C, Lester J, McAlister GK, Hall RJ, Burdine JA, Gotto AM. Effects of stress management training and dietary changes in treating ischaemic heart disease. JAMA 1993;249:54–60.

W. Linden / Journal of Psychosomatic Research 48 (2000) 443–454 [8] Ornish D, Brown SE, Scherwitz LS, Billings JH, Armstrong WT, Ports TA, McLanahan SM, Kirkeeide RL, Brand RJ, Gould KL. Can lifestyle change reverse coronary heart disease? Lancet 1990;336:129–133. [9] Friedman M, Thoreson C, Gill J, Powell L, Ulmer D, Thompson L, Price V, Rabin D, Breall W, Dixon T, Levy R, Bourg E. Alteration of type A behavior and reduction in cardiac recurrences in post-myocardial infarction patients. Am Heart J 1984; 108:237–248. [10] Frasure-Smith N, Prince R. The Ischemic Heart Disease Life Stress Monitoring Program: impact on mortality. Psychosom Med 1985;47:431–445. [11] Frasure-Smith N, Prince R. Long-term follow-up of the Ischemic Heart Disease Life Stress Monitoring Program. Psychosom Med 1989;51:485–513. [12] Blumenthal JA, Emery CF. Rehabilitation of patients following myocardial infarction. J Consult Clin Psychol 1988;56:374–381. [13] Ornish D. Dr. Dean Ornish’s program for reversing heart disease. New York: Random House 1990. [14] Frasure-Smith N. In-hospital symptoms of psychological stress as predictors of long- term outcome after acute myocardial infarction in men. Am J Cardiol 1991;67:121–127. [15] Frasure-Smith N, Lesperance F, Prince RH, Verrier P, Garber RA, Juneau M, Wolfson C, Bourassa MG. Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction. Lancet 1997;350:473–479. [16] Van Dixhoorn J, Duivenvoorden HJ, Staal HA, Pool J, Verhage F. Cardiac events after myocardial infarction: possible effects of relaxation therapy. Eur Heart J 1987;8:1210–1214. [17] Van Dixhoorn J, Duivenvoorden HJ, Staal HA, Pool J. Physical training and relaxation therapy in cardiac rehabilitation assessed through a composite criterion for training outcome. Am Heart J 1989;118:545–552. [18] Van Dixhoorn J, Duivenvoorden HJ, Pool J, Verhage F. Psychic effects of physical training and relaxation therapy after myocardial infarction. J Psychosom Res 1990;34:327–337. [19] Van Dixhoorn J, Duivenvoorden HJ, Pool J. Success and failure of exercise training after myocardial infarction: is the outcome predictable? J Am Coll Cardiol 1990;15:974–982. [20] Sakakibara M, Takeuchi S, Hayano J. Effect of relaxation training on cardiac sympathetic tone. Psychophysiology 1994;31: 223–228. [21] Sakakibara M, Hayano J. Effect of slowed respiration on cardiac parasympathetic response to threat. Psychosom Med 1996;58: 32–37 [22] Linden W. Autogenic training: a clinical guide. New York: Guilford Press 1990. [23] Horsten M, Ericson M, Perski A, Wamala SP, Schenck-Gustafson K, Orth-Gomer K. Psychosocial factors and heart rate variability in healthy women. Psychosom Med 1999;61:49–57. [24] Freedland KE, Carney RM, Hance ML, Skala JA. Cognitive therapy for depression in patients with coronary artery disease. Psychosom Med 1996;58:93. [25] Powell L. The ENRICHD trial. Paper presented at the American Psychosomatic Meeting, Santa Fe, NM 1997. [26] Denollet J, Sys SU, Brutsaert DL. Personality and mortality after myocardial infarction. Psychosom Med 1995;57:582–591. [27] Denollet JK. Repressive coping predicts mortality in patients with coronary heart disease (CHD). Paper presented at the American Psychosomatic Society Conference, Vancouver, BC 1999. [28] Oldridge N, Furlong W, Feeny D, Torrance G, Guyatt G, Crowe J, Jones N . Economic evaluation of cardiac rehabilitation soon after acute myocardial infarction. Am J Cardiol 1993;72:154–161. [29] Razin AM. Psychosocial intervention in coronary disease: a review. Psychosom Med 1982;44:363–381. [30] Hill DR, Kelleher K, Shumaker SA. Psychosocial interventions in adult patients with coronary heart disease and cancer. Gen Hosp Psychiatry 1992;14(suppl):28S–42S.

453

[31] Blumenthal JA, Wei J. Psychobehavioral treatment in cardiac rehabilitation. Cardiol Clin 1993;11:323–331. [32] Nunes EV, Frank KA, Kornfeld DS. Psychologic treatment for the type A behavior pattern and for coronary heart disease: a meta-analysis of the literature. Psychosom Med 1987;48:159–173. [33] Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. New Engl J Med 1992;327:248–254. [34] Oldridge NB, Guyatt GH, Fischer ME, Rimm AA. Cardiac rehabilitation after myocardial infarction: combined experience of randomized clinical trials. JAMA 1988;260:945–950. [35] Kugler J, Seelbach H, Krueskemper GM. Effects of rehabilitation exercise programmes on anxiety and depression in coronary patients. Br J Clin Psychol 1994;33:401–410. [36] Ketterer M. Secondary prevention of ischemic heart disease: the case for aggresive behavioral monitoring and intervention. Psychosomatics 1993;34:478–484. [37] Linden W, Stossel C, Maurice J. Psychosocial interventions for patients with coronary artery disease: a meta-analysis. Arch Int Med 1996;156:745–752. [39] Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141–145. [40] Jones DA, West RR. Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial. BMJ 1996;313:1517–1521. [41] Dusseldorp E, Van Elderen T, Maes S, Meulman J, Kraail V. A meta-analysis of psycho-educational programs for coronary heart disease patients. Health Psychol (in press). [42] Blumenthal JA, Jiang W, Babyak MA, Krantz DS, Frid DJ, Coleman RE, Waugh R, Hanson M, Appelbaum M, O’Connor C, Morris JJ. Stress management and exercise training in cardiac patients with myocardial ischemia. Arch Int Med 1997;157: 2213–2223. [43] Ades PA. Decreased medical costs after cardiac rehabilitation. J Cardiopul Rehabil 1993;13:75–77. [44] Sotile WM. Psychosocial interventions for cardiopulmonary patients. Champaign, Illinois: Human Kinetics Press 1996. [45] McKelvie RS, Koon KT, McCartney N, Humen D, Montague T, Yusuf S. Effects of exercise training in patients with congestive heart failure: a critical review. J Am Coll Cardiol 1995;25: 789–796. [46] Wagdi P, Vuilliomonet A, Kaufmann U, Richter M, Bertel O. Ungenuegende Behandlungsdisziplin, Patienteninformation und Medikamentenverschreibung als Ursachen fuer die Notfallhospitalisation bei chronisch herzinsuffizienten Patienten. Schweiz Med Wochenschrift 1993;123:108–112. [47] Fonarow GC, Stevenson LW, Walden JA, Livingston NA, Steimle AE, Hamilton MA, Moriguchi J, Tillisch JH, Woo MA. Impact of a comprehensive heart failure management program on hospital readmission and functional of patients with advanced heart failure. J Am Coll Cardiol 1997;30:725–732. [48] Grady KL, Jalowiec A, White-Williams C, et al. Predictors of quality-of-life in patients with advanced heart failure awaiting transplantation. J Heart Lung Transpl 1995;14:1–10. [49] Kostis JB, Rosen RC, Cosgrove NM, Shindler DM, Wilson AC. Nonpharmacologic therapy improves functional and emotional status in congestive heart failure. Chest 1994;106:995–1001. [50] Sullivan MJ, Hawthorne MH. Nonpharmacologic interventions in the treatment of heart failure. J Cardiovasc Nurs 1996; 10:47–57. [51] Moser DK. Maximizing therapy in the advanced heart failure patient. J Cardiovasc Nurs 1996;10:29–46. [52] Davies RA, Rivard M, Pflugfelder P, Teo K, Jlain B, Champagne F, Contandriopouos AP, Carrier M, Latter D, Chartrand C, Daly V, Gudas V, Poirier N, Sullivan J, Kostuk W. Heart transplantation in Canada and determinants of survival. Paper presented

454

W. Linden / Journal of Psychosomatic Research 48 (2000) 443–454

at the annual meeting of the Canadian Cardiovascular Society, Montreal 1996. [53] Dracup K, Walden J, Stevenson L, et al. Quality of life in patients with advanced heart failure. J Heart Lung Transplant 1992;11: 273–279. [54] Kop W. Chronic and acute psychologica risk factors for clinical manifestations of coronary artery disease. Psychosom Med 1999; 61:476–487. [55] Helgeson V, Fritz H. Cognitive adaptation as a predictor of new coronary events after percutaneous transluminal coronary angioplasty. Psychosom Med 1999;61:488–495.

[56] Appels A, Bar F, Lasker J, Flamm U, Kop W. The effect of a psychological intervention program on the the risk of a new coronory event after angioplasty: a feasibility study. J Psychosom Res 1997;43:209–217. [57] Frasure-Smith N, Lesperance F, Talajic M. Depression and 18month prognosis after myocardial infarction. Circulation 1995;91: 999–1005.