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Published online before print July 16, 2007, 10.1097/PSY.0b013e3180cabc73
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Psychosomatic Medicine 69:495-500 (2007)
© 2007 American Psychosomatic Society

ORIGINAL ARTICLES

Mental Stress Hemodynamic Responses and Myocardial Ischemia: Does Left Ventricular Dysfunction Alter These Relationships?

Sari D. Holmes, MS, David S. Krantz, PhD, Willem J. Kop, PhD, Albert Del Negro, MD, Pamela Karasik, MD and John S. Gottdiener, MD, FACC

From the Uniformed Services University of the Health Sciences (S.D.H., D.S.K.), Bethesda, Maryland; University of Maryland Medical Center (W.J.K., J.S.G.), Baltimore, Maryland; Veterans Affairs Medical Center (P.K.), Washington, DC; and Arrhythmia Associates and INOVA Fairfax Hospital (A.D.N.), Fairfax, Virginia.

Address correspondence and reprint requests to Sari D. Holmes, Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, 4301 Jones Bridge Rd., Bethesda, MD 20814. E-mail: sholmes{at}usuhs.mil


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Objective: To assess if mental stress hemodynamic responses are impaired and related to mental stress (MS) ischemia in patients with left ventricular (LV) dysfunction.

Background: Impaired LV function is an important coronary artery disease (CAD) risk factor and hemodynamic characteristics play an important role in clinical outcomes. Patients with severe LV dysfunction (SLVD) are frequently excluded from prior studies and the effects of LV dysfunction on MS hemodynamic responses are not known.

Methods: Fifty-eight patients with CAD, consisting of 22 patients with normal LV function (ejection fraction (EF) ≥50%), 16 patients with mild-to-moderate LV dysfunction (30% < EF < 50%), and 20 patients with severe LV dysfunction (EF ≤30) underwent bicycle exercise (EX) and MS testing with 12-lead electrocardiogram and monitoring of vital signs on consecutive days in random order. Blood pressure and heart rate (HR) measurements were obtained. Ischemia was measured using single photon emission computed tomography.

Results: Both MS and EX produced significant increases in all hemodynamic measurements. HR levels were higher both at rest and during MS in SLVD patients. LV groups increased similarly from rest to stress (both MS and EX) for all measurements except HR during MS, which increased more in patients with SLVD than patients with normal LV function. Hemodynamic responses to MS were not related to myocardial ischemia or heart failure symptoms.

Conclusions: HR response during MS is increased in patients with SLVD, whereas blood pressure responses are similar to those in patients with preserved LV function. Hemodynamic reactivity is unrelated to MS-induced ischemia.

Key Words: mental stress • left ventricular dysfunction • hemodynamics • ischemia • coronary artery disease

Abbreviations: CAD = coronary artery disease; ICD = implantable cardioverter defibrillator; MI = myocardial infarction; ECG = electrocardiogram; LV = left ventricular; EF = ejection fraction; SVR = systemic vascular resistance; DP = double product; NYHA = New York Heart Association; SPECT = single photon emission computed tomography; EX = exercise; MS = mental stress; SLVD = severe left ventricular dysfunction; MLVD = mild-to-moderate left ventricular dysfunction; NLVF = normal left ventricular function.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Impaired left ventricular (LV) function is an important predictor of clinical outcomes in patients with coronary artery disease (CAD) (1,2). In patients with LV dysfunction, which is often associated with heart failure, the body compensates to maintain the cardiac output including activation of the sympathetic nervous system (SNS) (3). Prior studies suggested that acute psychological stress can result in impaired LV function and myocardial ischemia (4–6). However, little is known about the hemodynamic responses to mental stress (MS) in patients with severely reduced LV function because these patients have not been included in prior studies (4,7,8).

In comparison with exercise (EX) testing in patients with CAD and normal LV function, MS produces smaller increases in systolic blood pressure (SBP), heart rate (HR), and double product (DP) and larger increases in diastolic blood pressure (DBP) (8–11). These hemodynamic changes serve as compensatory processes to increase cardiac output and improve peripheral blood flow. In patients with LV dysfunction, psychological and physical stressors might produce increases in cardiac demand and total systemic resistance. These responses may have adverse effects on cardiac function. LV dysfunction (i.e., left ventricular ejection fraction <30%), with or without heart failure, is associated with increased SNS activation (12). The consequences of EX are well understood in heart failure and reduced LV function. However, only a few studies, in selected populations, have examined the effects of impaired LV function on hemodynamic responses to MS and have yielded conflicting results. A study of New York Heart Association (NYHA) class III heart failure patients with dilated cardiomyopathy found that opioid levels, blood pressure, HR, and norepinephrine increased in response to stress (12), but the extent of LV dysfunction was not examined in this study. In contrast, research in patients with severe (NYHA class III–IV) heart failure found that those with heart failure showed blunted HR increases and higher levels of sympathetic activation at rest and during MS compared with normal age-matched controls (13). Patients in this study had end-stage heart failure and their responsiveness to stress was blunted by the failure of the heart to pump because there was such severe cardiac damage. A lesser degree of LV dysfunction is much more common in patients with CAD and life-threatening failure of the heart as a pump is not present in these individuals. In the absence of existing data, it is possible to predict that increased resting sympathetic activity in these individuals could lead to increased hemodynamic responses, or in contrast, the reduced ability of the heart to pump might be associated with decreased stress reactivity.

Studies indicate that MS induces myocardial ischemia in a substantial subset of patients with CAD (4–9,14,15) and we demonstrated that MS-induced myocardial ischemia is more prevalent in patients with LV dysfunction (16). Most of the studies (8,15) that have used ventricular function as the marker of ischemia have found that increased hemodynamic responses are associated with susceptibility to MS-induced ischemia. Assessment of myocardial ischemia based on changes in ventricular function is not appropriate in patients with severely impaired LV function. Investigation of MS-induced ischemia using myocardial perfusion imaging enables accurate detection of ischemia in the presence of LV dysfunction. At least two studies (17,18) using perfusion imaging have not found that hemodynamic responses to MS were predictive of myocardial perfusion defects.

Previously, we examined exercise and mental stress-induced ischemia in this sample using myocardial perfusion imaging (16). The current analyses compare hemodynamic responses to MS and EX in a sample of patients with CAD and normal left ventricular function (NLVF), mild-to-moderate left ventricular dysfunction (MLVD), or severe left ventricular dysfunction (SLVD) (16). MS-induced ischemia is measured using myocardial perfusion imaging. The aims of the present report are: a) to assess the hemodynamic responses to MS in patients with LV dysfunction (without severe clinical heart failure) compared with those with normal or moderately impaired LV function; b) to determine how patients' hemodynamic response to MS compares with EX responses in these patient groups; and c) to compare hemodynamic responses to MS between those with and without MS-induced ischemia.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Subjects
Patients with documented CAD (n = 58) were recruited as part of a multicenter study on Triggers of Arrhythmia in Defibrillator patients conducted between 2001 and 2005. Patient characteristics and study procedures for this sample are described elsewhere (16). There were 20 patients with severe LV dysfunction (ejection fraction (EF) ≤30%), 16 with MLVD (30% < EF < 50%), and 22 patients with NLVF (EF ≥50%). To examine how patients with these three levels of LV function respond to MS and EX, patients were categorized into LV function groups based on clinically relevant cut-points used in prior research (19–21). These cut-points also corresponded to tertile classifications for this sample.

Exclusion criteria were nonischemic cardiomyopathy, recent myocardial infarction (MI) (<1 month), recent percutaneous coronary angioplasty, planned coronary artery bypass surgery, severe (class IV) congestive heart failure, stroke, atrial fibrillation, left bundle-branch block, significant neurological or psychiatric abnormality, unstable angina, and critical valvular pathology. Implantable cardioverter defibrillators (ICDs) were present in 41 of the 58 patients in this analysis. The two LV dysfunction groups had more patients with ICDs as compared with the normal LV function group (p < .05), but reasons for device implantation were not different between the groups (Table 1).


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  		TABLE 1. Clinical and Demographic Characteristics

 

ß-adrenergic blocking agents, long-acting nitrates, calcium antagonists, and angiotensin-converting enzyme inhibitors were withheld when tolerated (22,23). Thirty-one patients were tested on ß-adrenergic blocking agents, eight patients were tested on long-acting nitrates, six patients were tested on calcium antagonists, and 30 patients were tested on angiotensin-converting enzyme inhibitors.


Study Procedures
This study was approved by the Institutional Review Boards at the participating institutions and written informed consent was obtained from participants. Participants underwent bicycle EX and MS testing with hemodynamic assessment on consecutive days in random order. On both testing days, participants were connected to a 12-lead electrocardiogram (ECG) and automated blood pressure monitor. During a rest period on each day, measurements of SBP, DBP, and HR were taken at 30 seconds, 2.5 minutes, and then every 2 minutes until approximately 20 minutes had elapsed.

Mental Stress
Subjects were asked to recall a recent anger-provoking incident and discuss the circumstances of the incident in the presence of the research team (24). Next, a 4-minute math task was administered (23). Patients subtracted 7 serially from 1000 and they were reminded to answer quickly. Patients were notified immediately, whenever they made a mistake, and were then asked to give the correct answer. Blood pressure and HR measurements were obtained at 30 seconds, 2 minutes, and 3.5 minutes during both tasks. Anger recall was used as the MS task for these analyses because the results for the math task were no different from the anger recall task and the perfusion data were obtained during anger recall.

Bicycle Stress Test
Subjects pedaled a bike to match the beat of a metronome. EX was terminated for the following reasons: the patient developed moderate chest pain, shortness of breath, >2 mm horizontal or downsloping ST segment depression, severe ventricular arrhythmias, hypotension, excessive fatigue, or if 80% of maximum HR was reached and maintained. Pedal resistance began at 25 watts and increased by 25 watts every 3 minutes until the patient attained maximal effort tolerance (80% of maximum HR). This EX test was chosen over a treadmill test because of requirements for measuring ECG parameters in the study and for feasibility concerns with the inclusion of the SLVD group in our study. Blood pressure and HR measurements were taken at 2.5 minutes and every 3 minutes until 11.5 minutes had elapsed or the patient was unable to continue exercising.

Myocardial Ischemia Assessment
A description of myocardial ischemia assessment for this study is presented elsewhere (16). Dual isotope single-photon emission CT (SPECT) was used to assess myocardial ischemia due to the benefits of perfusion measurements in patients with reduced LV function (16,25). Thallium-201 (2.5 to 3.5 mCi) was injected at rest and 20 to 30 mCi of technetium-99m sestamibi was injected during MS and EX (25). A dual-head SPECT camera obtained myocardial perfusion images.

Statistical Analysis
Results are expressed as mean ± SD values or percentages where appropriate. Double product (DP) was calculated for each rest and stress time point (SBP x HR). Changes in hemodynamic indices in response to EX were calculated as rest to peak, whereas hemodynamic reactivity to MS used rest to mean responses. Student's dependent t tests on difference scores (rest to stress) were used to compare MS to EX on changes in blood pressure, HR, and DP. Differences between LV dysfunction groups on continuous demographic, disease severity, and hemodynamic response measures were assessed by univariate and repeated measures analyses of variance (ANOVAs) with Tukey's post hoc tests and simple contrast tests where applicable. The time factor for the repeated-measures ANOVAs was represented by two levels, rest to stress (MS or EX). Differences between LV dysfunction groups on categorical demographic and disease severity measures were assessed by logistic regression. A two-tailed {alpha} value of p < .05 was adopted in all analyses, unless otherwise noted.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 NOTES
 REFERENCES
 
Clinical and Demographic Characteristics
Age, gender, race, and clinical characteristics were similar across the three LV dysfunction groups (Table 1) with a few exceptions. Although education was significantly higher in the NLVF group as compared with the other two LV groups (F(2,48) = 5.28, p < .01), analyses covarying for education did not differ from the analyses to be reported. Prior MIs were more prevalent in patients with SLVD than with NLVF (OR = 19.80; p < .01) (Table 1). In addition, ICDs were more prevalent in the SLVD and MLVD groups as compared with the NLVF group (OR = 27.78; p < .01; and OR = 20.41; p < .01). The severity of anginal complaints and extent of angiographic disease assessed qualitatively were not statistically different between the three groups. All patients had a history of stable angina. Antihypertensive and anti-ischemic medication usage was not significantly different between the LV dysfunction groups (Table 1).

Hemodynamics: Exercise Versus MS and Effects of LV Dysfunction
MS and EX produced significant increases in SBP, DBP, HR, and DP (p < .001), with all LV groups increasing from rest to stress for all hemodynamic measurements (16). LV group by time interactions demonstrated that each group increased similarly from rest to stress (MS and EX) for all hemodynamic measurements (p > .05) (Figure 1). However, a contrast test to investigate the relationship described by Middlekauff and colleagues (13) showed that, for MS, the SLVD group increased significantly more in HR from rest to stress than the NLVF group (p = .046), although the overall test was not significant (F(2, 55) = 2.09; p = .13). Using a continuous measurement of EF, analyses of MS hemodynamic change scores also found that EF was negatively correlated with HR change scores (r(56) = –.26; p = .05), but not significantly correlated with SBP (r(56) = .16; p = .22) or DBP (r(56) = –.06; p = .65) change scores.


Figure 13
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  		Figure 1. Hemodynamic responses to rest, mental stress, and exercise across left ventricular function groups (mean ± SD); heart rate expressed as beats/min; systolic and diastolic blood pressures expressed as mm Hg)

 

Table 2 displays EX hemodynamic results for each LV group separately. Maximal bicycle workload achieved decreased as a function of LV group (F(2,55) = 5.14; p < .01); however, significant differences in workload were found only for comparisons between the normal LV function and severe LV dysfunction groups (p = .01). Moreover, comparable numbers of patients in each group reached age-predicted maximum HRs during EX (p > .80). Maximal EX SBP and DBP and HRs were not different between the three groups (F(2,54) = 0.42, p = .66; F(2,54) = 0.13, p = .88; F(2,55) = 0.78, p = .46, respectively). One patient from each LV function group reported angina during EX. There were significant ST segment depressions during EX in eight patients, but there were no differences between the LV groups (NLVF versus SLVD: OR = 0.18, p = .13; NLVF versus MLVD: OR = 0.49, p = .43; SLVD versus MLVD: OR = 2.71, p = .43).


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  		TABLE 2. Exercise Hemodynamic Results

 

Table 3 outlines MS hemodynamic results by LV group. For MS, mean HR achieved during the task differed as a function of LV group (F(2, 55) = 5.48; p = .007), with HRs higher in severe LV dysfunction group than in normal LV function group (p = .005). There was no significant difference between the three groups in mean blood pressure (F(2,55) = 1.05, p = .357 and F(2,55) = 0.69, p = .505) or DPs (F(2,55) = 1.99; p = .146) attained during MS. No patients reported chest pain or had ST segment depression during MS.


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  		TABLE 3. Mental Stress Hemodynamic Results

 

For the entire sample, HR (t(57) = –16.33; p < .001) and DP (t(56) = –11.83; p < .001) increased more with EX than with MS, whereas DBP (t(56) = 3.85; p < .001) increased significantly more in MS than EX and SBP increased similarly for EX and MS (t(56) = –0.03; p = .98). For all three LV groups separately, HR and DP increased significantly more with EX than MS (p < .001). DBP increased significantly more with MS than EX in the NLVF and SLVD groups (t(21) = 2.09, p = .049 and t(19) = 2.76, p = .013). There was a marginal difference in EX versus MS DBP increase for the MLVD group (t(14) = 1.78; p = .096). SBP increased similarly for EX and MS for all three LV groups (p > .10)

Effects of Ischemia on MS Hemodynamics
We next assessed hemodynamic responses to MS as a function of whether patients developed ischemia during MS as well as by heart failure clinical status. Myocardial ischemia data, defined as myocardial perfusion defects using SPECT imaging, are reported elsewhere (16). The present analyses indicated that those with myocardial ischemia versus those without myocardial ischemia were comparable on baseline hemodynamic measurements (p > .20). Ischemia status by time interactions demonstrated that hemodynamic responses to MS were comparable among those patients who did versus did not show evidence of myocardial ischemia (Table 4)—HR: F(1,56) = 0.02, p = .89; SBP: F(1,56) = 2.66, p = .11; DBP: F(1, 56) = 0.52, p = .47). This hemodynamic response relationship held up across LV function groups. Similarly, heart failure symptoms by time interactions demonstrated that hemodynamic responses to MS were not associated with the presence of heart failure clinical symptoms (HR: F(2,53) = 1.60, p = .21; SBP: F(2,53) = 2.09, p = .13; DBP: F(2,53) = 0.60, p = .55).


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  		TABLE 4. Mental Stress Hemodynamics by Ischemia Presence

 


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
NOTES
 REFERENCES
 
In this study, patients with SLVD (EF ≤ 30) without class IV heart failure displayed increased HRs, but not increased blood pressure during rest and MS compared with those with normal LV function. HR was not significantly higher at peak EX for SLVD compared with the other groups. This result could be due to the significantly lower workloads achieved during EX by the SLVD group as compared with the NLVF group. In addition, the comparisons of hemodynamic responses with MS versus EX found that, across LV function groups, HR and DP increases were higher in EX; DBP increases were greater in MS; and there was no significant difference in SBP increases between EX and MS. Although this finding has been reported previously, it is important to note that the addition of the SLVD group in this study did not alter the direction of any of these comparisons from what would be expected based on NLVF.

In addition to higher absolute magnitude of HR at rest and during MS in the SLVD group compared with the NLVF group, HR stress reactivity was greater in the SLVD versus NLVF patients. A prior report of blunted HR response to MS (13) may reflect much more advanced stages of heart failure (NYHA classes III–IV) and impaired left ventricular pump function. Perhaps patients with LV dysfunction and heart failure class III or lower have greater physiological capacity to respond to a mental stressor than those with advanced heart failure. It is also possible that the difference in the control group, healthy controls in the previous study (13), and NLVF patients with CAD here did not allow for an appropriate comparison of results. However, responses in this study are comparable in magnitude with those observed in other investigations of patients with CAD (7–9,15). Given the role of the SNS in LV dysfunction, it is likely that the increased HRs during rest and MS reflect increased SNS function in those with SLVD. In addition, these increased HR levels during rest and MS may account for some of the increased risk of morbidity and mortality in patients with LV dysfunction, by way of the increased SNS activity (26). Thus, in contrast to the previous study of patients with class IV heart failure (13), this study demonstrated that hemodynamic increases can be induced by MS in these SLVD patients with similar or greater intensity to those with NLVF.

An important aim of this study was to determine if hemodynamic stress responses were predictive of MS-induced ischemia, especially in the SLVD group. Similar hemodynamic responses to MS were observed between those who demonstrated ischemia to MS and those who did not. There are several possible explanations for this finding. First, this study, in contrast to others, systematically investigated patients with SLVD. Second, measures of ischemia based on LV dysfunction may be related to hemodynamic response, whereas myocardial perfusion defects, assessed in this study, do not show a similar relationship to hemodynamic increases. Because the SPECT perfusion measure is a more sensitive test, it allows for detection of ischemia that occurs without large hemodynamic changes as well as less severe ischemia compared with measures of ventricular contractile function. In this regard, the one study (9) reporting associations of increased MS hemodynamic responses to ischemia using SPECT was based on EX-induced ischemia, which is not comparable to the present analyses using MS-induced ischemia.

The finding that DBP responses to MS were greater than responses to EX for all LV function groups may also be of particular importance. This result implies that MS has a greater effect on systemic vascular resistance (SVR) than EX. The fact that those with SLVD demonstrated this response pattern may indicate that MS can lead to more detrimental consequences than EX in these patients. Mental stressors could lead to increases in SVR, which would increase pressure and cause the heart to work harder—an undesirable effect in patients with LV dysfunction. For example, these hemodynamic changes to MS increase afterload and myocardial demand, which increase vulnerability to stress-induced ischemia (6,8,9,15) and heart failure symptoms.

These findings regarding hemodynamic responses to MS and EX may be limited to patients with implantable ICDs and might not be generalizable to all patients with CAD. In addition, it is possible that the bicycle EX protocol that was used was not adequate for patients to achieve comparable workloads as found with other forms of EX stress testing. Although most patients did not achieve age-predicted HRs, maximal EX HRs did not differ between the groups.

Most pharmacologic therapy in heart failure is directed at decreasing blood pressure and reducing SVR (27). Because DBP is increased with MS more than with EX, MS may have particularly negative consequences as a result of increased blood pressure and SVR. In addition, prior studies have demonstrated that MS hemodynamic responses are predictive of future clinical events in patients CAD and NLVF. Clinical and prognostic significance in patients with impaired LV function is warranted.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
REFERENCES
 
The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the Uniformed Services University of the Health Sciences or the US Department of Defense.

Preparation of this paper was supported, in part, by Grants HL47337 (D.S.K.) and T32HL069751 (D.S.K.) from the National Institutes of Health.

Received for publication April 3, 2006; revision received April 5, 2007.

DOI:10.1097/PSY.0b013e3180cabc73


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

  1. Rouleau JL, Talajic M, Sussex B, Potvin L, Warnica W, Davies RF, Gardner M, Stewart D, Plante S, Dupuis R, Lauzon C, Ferguson J, Mikes E, Balnozan V, Savard P. Myocardial infarction patients in the 1990s—their risk factors, stratification and survival in Canada: the Canadian assessment of myocardial infarction (CAMI) Study. J Am Coll Cardiol 1996;27:1119–27.[Abstract]
  2. Solomon SD, Zelenkofske S, McMurray JJ, Finn PV, Velazquez E, Ertl G, Harsanyi A, Rouleau JL, Maggioni A, Kober L, White H, Van de Werf F, Pieper K, Califf RM, Pfeffer MA, Investigators ViAMITV. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005;352:2581–8.[Abstract/Free Full Text]
  3. Floras JS. Alterations in the sympathetic and parasympathetic nervous system in heart failure. In: Mann DL, editor. Heart failure: a companion to Braunwald's heart disease. Philadelphia, PA: Saunders; 2004.
  4. Rozanski A, Bairey CN, Krantz DS, Friedman J, Resser KJ, Morell M, Hilton-Chalfen S, Hestrin L, Bietendorf J, Berman DS. Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N Engl J Med 1988;318:1005–12.[Abstract]
  5. Gottdiener JS, Krantz DS, Howell RH, Hecht GM, Klein J, Falconer JJ, Rozanski A. Induction of silent myocardial ischemia with mental stress testing: relation to the triggers of ischemia during daily life activities and to ischemic functional severity. J Am Coll Cardiol 1994;24:1645–51.[Abstract]
  6. Jain D, Shaker SM, Burg M, Wackers FJ, Soufer R, Zaret BL. Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease. J Am Coll Cardiol 1998;31:1314–22.[Abstract/Free Full Text]
  7. Krantz DS, Helmers KF, Bairey CN, Nebel LE, Hedges SM, Rozanski A. Cardiovascular reactivity and mental stress-induced myocardial ischemia in patients with coronary artery disease. Psychosom Med 1991;53:1–12.[Abstract/Free Full Text]
  8. Goldberg AD, Becker LC, Bonsall R, Cohen JD, Ketterer MW, Kaufman PG, Krantz DS, Light KC, McMahon RP, Noreuil T, Pepine CJ, Raczynski J, Stone PH, Strother D, Taylor H, Sheps DS. Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the psychophysiological investigations of myocardial ischemia study (PIMI). Circulation 1996;94:2402–9.[Abstract/Free Full Text]
  9. Kral BG, Becker LC, Blumenthal RS, Aversano T, Fleisher LA, Yook RM, Becker DM. Exaggerated reactivity to mental stress is associated with exercise-induced myocardial ischemia in an asymptomatic high-risk population. Circulation 1997;96:4246–53.[Abstract/Free Full Text]
  10. Schoder H, Silverman DH, Campisi R, Karpman H, Phelps ME, Schelbert HR, Czernin J. Effect of mental stress on myocardial blood flow and vasomotion in patients with coronary artery disease. J Nucl Med 2000;41:11–6.[Abstract/Free Full Text]
  11. Okano Y, Utsunomiya T, Yano K. Effect of mental stress on hemodynamics and left ventricular diastolic function in patients with ischemic heart disease. Jpn Circ J 1998;62:173–7.[CrossRef][Medline]
  12. Fontana F, Bernardi P, Merlo Pich E, Tartuferi L, Boschi S, De Iasio R, Spampinato S. Opioid peptides in response to mental stress in asymptomatic dilated cardiomyopathy. Peptides 1998;19:1147–53.[CrossRef][Medline]
  13. Middlekauff HR, Nguyen AH, Negrao CE, Nitzsche EU, Hoh CK, Natterson BA, Hamilton MA, Fonarow GC, Hage A, Moriguchi JD. Impact of acute mental stress on sympathetic nerve activity and regional blood flow in advanced heart failure: implications for "triggering" adverse cardiac events. Circulation 1997;96:1835–42.[Abstract/Free Full Text]
  14. Kim CK, Bartholomew BA, Mastin ST, Taasan VC, Carson KM, Sheps DS. Detection and reproducibility of mental stress-induced myocardial ischemia with Tc-99m sestamibi SPECT in normal and coronary artery disease populations. J Nucl Cardiol 2003;10:56–62.[CrossRef][Medline]
  15. Blumenthal JA, Jiang W, Waugh RA, Frid DJ, Morris JJ, Coleman RE, Hanson M, Babyak M, Thyrum ET, Krantz DS, O'Connor C. Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life. Association and hemodynamic features. Circulation 1995;92:2102–8.[Abstract/Free Full Text]
  16. Akinboboye O, Krantz DS, Kop WJ, Schwartz SD, Levine J, Del Negro A, Karasik P, Berman DS, O'Callahan M, Ngai K, Gottdiener JS. Comparison of mental stress-induced myocardial ischemia in coronary artery disease patients with versus without left ventricular dysfunction. Am J Cardiol 2005;95:322–6.[CrossRef][Medline]
  17. Arrighi JA, Burg M, Cohen IS, Soufer R. Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease. J Nucl Cardiol 2003;10:267–74.[CrossRef][Medline]
  18. Ramachandruni S, Fillingim RB, McGorray SP, Schmalfuss CM, Cooper GR, Schofield RS, Sheps DS. Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia. J Am Coll Cardiol 2006;47:987–91.[Abstract/Free Full Text]
  19. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877–83.[Abstract/Free Full Text]
  20. O'Keefe JH Jr, Zinsmeister AR, Gibbons RJ. Value of normal electrocardiographic findings in predicting resting left ventricular function in patients with chest pain and suspected coronary artery disease. Am J Med 1989;86:658–62.[CrossRef][Medline]
  21. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol 1999;33:1948–55.[Abstract/Free Full Text]
  22. Jiang W, Blumenthal JA, Hanson MW, Coleman RE, Frid DJ, Waugh RA, Morris JJ, O'Connor CM. Relative safety of short-term antianginal medication withdrawal: relevance to clinical trials (abstract). J Am Coll Cardiol 1997;29:236.
  23. Kop WJ, Krantz DS, Howell RH, Ferguson MA, Papademetriou V, Lu D, Popma JJ, Quigley JF, Vernalis M, Gottdiener JS. Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses. J Am Coll Cardiol 2001;37:1359–66.[Abstract/Free Full Text]
  24. Ironson G, Taylor CB, Boltwood M, Bartzokis T, Dennis C, Chesney M, Spitzer S, Segall GM. Effects of anger on left ventricular ejection fraction in coronary artery disease. Am J Cardiol 1992;70:281–5.[CrossRef][Medline]
  25. Berman DS, Kiat H, Friedman JD, Wang FP, van Train K, Matzer L, Maddahi J, Germano G. Separate acquisition rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: a clinical validation study. J Am Coll Cardiol 1993;22:1455–64.[Abstract]
  26. Palatini P, Julius S. Elevated heart rate: a major risk factor for cardiovascular disease. Clin Exp Hypertens 2004;26:637–44.[CrossRef][Medline]
  27. Klein L, O'Connor CM, Gattis WA, Zampino M, de Luca L, Vitarelli A, Fedele F, Gheorghiade M. Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. Am J Cardiol 2003;91:18F–40F.[Medline]



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Psychological Stress and Myocardial Ischemia: Understanding the Link and the Implications
Psychosom Med, July 1, 2007; 69(6): 491 - 492.
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