Sestamibi Myocardial Perfusion Imaging Research Articles

Sublingual glyceryl trinitrate given during adenosine sestamibi myocardial perfusion imaging causes apparent transient ischaemic dilation in a propensity-matched analysis.

Administration of sublingual glyceryl trinitrate (GTN) prior to resting radiotracer injection during myocardial perfusion imaging (MPI) has been advocated to aid detection of viable myocardium and increase the extent of reversible perfusion defects. However, GTN is also known to reduce resting left ventricular volume and could thus increase the transient ischaemic dilation (TID) ratio, independently of severe or extensive coronary artery disease. We aimed to determine if GTN administration causes an increase in the TID ratio. Causal inference using propensity score matched analysis was used to assess the effect of GTN on TID ratios in subjects undergoing adenosine sestamibi MPI. From 597 consecutive patients undergoing MPI, we selected a treatment group of 51 who received 400 μg of sublingual GTN before resting sestamibi injection and 51 propensity score matched controls. Mean TID ratios were 1.24 in treated subjects and 1.10 in controls (mean difference 0.15; 95% CI, 0.05-0.25; P = 0.0018). The mean difference in TID ratio fell progressively in each quartile of time elapsed between GTN administration and image acquisition. The proportion with TID ratios equal and greater than an abnormal threshold of 1.39 was 17.6% among the treated and 0% in controls (P = 0.0010). The effect on TID ratio was not restricted to those with moderate-to-severe stress perfusion defects or accompanied by greater reversible perfusion defects. There is evidence of a cause-and-effect relationship between administering GTN before resting sestamibi injection and increased TID ratio on MPI. This may be a source of misleading false positive TID findings.

Tc-99m Sestamibi Myocardial Perfusion Imaging After Coronary Artery Bypass Grafting for Ischemic Heart Failure

Heart failure (HF), a clinical syndrome most commonly occurring due to ischemic heart disease, causes significant morbidity and mortality. The benefits of revascularization versus medical treatment for ischemic heart failure remain controversial. Thus, we assessed a patient diagnosed with ischemic heart failure before and 3 months after coronary artery bypass grafting by myocardial radionuclide imaging. Findings of Tc-99m sestamibi myocardial perfusion imaging revealed that the degree and area of ischemia were significantly reduced, and the systolic function of the left ventricle improved compared with the preoperative value. This suggests the benefit of revascularization in cases of ischemic heart failure.

Relation of High-sensitivity Cardiac Troponin I Elevation With Exercise to Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease

High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging with treadmill testing. Plasma hs-cTnI level was measured at rest and at 45 min after stress. Multivariable Fine & Gray's subdistribution hazards models were used to determine the association between the change in hs-cTnI and MACE, a composite end point of cardiovascular death, myocardial infarction, and unstable angina requiring revascularization. During a median follow-up of 3 years, 39 (11%) patients experienced MACE. After adjustment, for each two-fold increment in hs-cTnI with stress, there was a 2.2 (95% confidence interval 1.3-3.6)-fold increase in the hazard for MACE. Presence of both a high resting hs-cTnI level (>median) and ≥ 20% stress-induced hs-cTnI elevation was associated with the highest incidence of MACE (subdistribution hazards models 4.6, 95% confidence interval 1.6 to 13.0) compared with low levels of both. Risk discrimination statistics significantly improved after addition of resting and change in hs-cTnI levels to a model including traditional risk factors and inducible ischemia (0.67 to 0.71). Conversely, adding inducible ischemia by SPECT did not significantly improve the C-statistic from a model including traditional risk factors, baseline and change in hs-cTnI (0.70 to 0.71). In stable CAD patients, higher resting levels and elevation of hs-cTnI with exercise are predictors of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors and presence of inducible ischemia.

Association of Posttraumatic Stress Disorder With Mental Stress–Induced Myocardial Ischemia in Adults After Myocardial Infarction

Posttraumatic stress disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear. To evaluate the association of PTSD with mental stress-induced myocardial ischemia among individuals who survived a myocardial infarction (MI). This cross-sectional study included 303 patients aged 18 to 60 years enrolled from a university-affiliated network. Participants had a verified history of MI within 8 months. Data were collected from June 2011 to March 2016, and data analysis was conducted from March to June 2019. A clinical diagnosis of PTSD (lifetime and current) was obtained using the Structured Clinical Interview from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and PTSD symptom subscales were assessed with the civilian version of the PTSD Symptom Checklist. Patients received technetium 99m-labeled sestamibi myocardial perfusion imaging at rest, with mental stress (ie, a speech task) and conventional stress (ie, exercise or pharmacologic). A summed difference score (ie, the difference between stress and rest scores) was used to assess ischemia under both stress conditions. Among 303 participants (148 [48.8%] women; 198 [65.3%] African American; mean [SD] age, 51 [7] years), the prevalence of PTSD was 14.5% (44 patients). Patients with PTSD had a higher rate of ischemia with mental stress than those without PTSD (12 of 44 [27.3%] vs 38 of 259 [14.7%]; P = .04) and more than twice the mean number of ischemic segments (1.2 [95% CI, 0.5-1.8] vs 0.5 [95% CI, 0.3-0.7]; P < .001), but there was no difference in conventional stress ischemia (10 of 44 [22.7%] vs 60 of 259 [23.2%]; P = .91). Increasing levels of PTSD symptoms were associated with higher odds of ischemia with mental stress (adjusted odds ratio [OR] per 5-point score increase, 1.18; 95% CI 1.04-1.35; P = .01) but not with conventional stress (adjusted OR per 5-point score increase, 1.05; 95% CI, 0.92-1.21; P = .47). Reexperiencing trauma was the symptom cluster most robustly associated with the presence of ischemia with mental stress (adjusted OR per 5-point score increase, 1.87; 95% CI 1.21-2.91; P = .005), followed by avoidance and numbing (adjusted OR per 5-point score increase, 1.51; 95% CI, 1.07-2.14; P = .02). In this study of young and middle-aged individuals with MI, with a large representation of women and patients from racial/ethnic minority groups, PTSD was associated with the development of myocardial ischemia with mental stress. A higher ischemic response to mental stress represents a potential pathway associating PTSD with adverse outcomes after MI.

Assessment of viable myocardium by nitrate-augmented technetium-99m sestamibi myocardial perfusion imaging

Objective The aim of this study was to assess the role of nitrate-augmented technetium-99m (99mTc) sestamibi imaging in the evaluation of viable myocardium in patients who had ischemic heart disease with depressed left ventricle (LV) systolic function. Background In the setting of acute myocardial infarction, stunning can occur, which is the persistent LV dysfunction following opening of the occluded coronary artery; recovery of function occurs usually within months. In the setting of chronic LV dysfunction, the pathophysiology underlying the dysfunction is referred to as myocardial hibernation. Various imaging techniques have been introduced to detect viability and discriminate this from scar tissue. Patients and methods Between November 2015 and November 2016, 100 patients with a history of myocardial infarction 'functional class II and III' or/and LV dysfunction were included in this multicenter prospective study. All patients underwent 99mTc sestamibi myocardial perfusion imaging under both rest and rest with nitrate conditions. Results Nitrates improved viability detection by myocardial perfusion imaging in patients with depressed LV systolic function. There was significant decrease in the total perfusion defect in rest with nitrate study in comparison with the rest study (P = 0.006). Conclusion In patients with chronic ischemic heart disease with depressed LV systolic function, the use of nitrate-augmented Tc-99m sestamibi protocol in cardiac single photon emission computed tomography imaging results in improved detection of viable but hypoperfused segments. It is a good indicator for differentiating viable tissues from the scar.

Abnormal Heart Rate Recovery as a Predictor of Coronary Artery Disease in Patients Undergoing Exercise Stress Myocardial Perfusion Imaging: A 4-Year Retrospective Study in Chong Hua Hospital

Background: Abnormal heart rate recovery (HRR) after exercise is associated with an increase in all-cause mortality in both asymptomatic individuals and patients with established heart disease. In clinical practice, myocardial perfusion imaging (MPI) is used to establish the diagnosis and prognosis of coronary artery disease (CAD). This study aimed to determine the relationship between the HRR and the MPI findings of patients who underwent exercise stress test using sestamibi MPI. Methods: This was a four-year retrospective chart review study that included all patients who underwent exercise stress test using the sestamibi MPI at Chong Hua Hospital from January 2014 through December 2017. HRR was computed as the difference between peak HR and HR at the 60th second. Abnormal HRR was defined as either &lt;12 beats per minute (bpm) from the peak HR after one minute with post-exercise cooldown. Patient demographics and clinical factors were reviewed and analyzed using parametric and nonparametric statistical tools. Results: A total of 304 patients were included in the study: 68% were male, 86% were aged &gt;40 years. The most common comorbidity was combined hypertension and dyslipidemia (35%). The mean HRR was 31 bpm, and the mean percentage of chronotropic response (PCR) was 86. Eighty-eight percent of the patients had normal HRR. Eighty-six percent had MPI results within normal ranges. The chi squared test results showed no significant relationship between HRR and the diagnosis of inducible ischemia (p=0.141). Conclusion: About 88% of the study subjects were identified with normal HRR, while only 12% were classified as having abnormal HRR. There was no significant correlation between HRR and MPI findings of inducible ischemia among Filipino who underwent exercise stress MPI in this study.

Scintigraphic findings in end-stage liver disease on Tc-99m sestamibi SPECT/CT myocardial perfusion imaging

Technetium-99m sestamibi myocardial perfusion imaging is commonly employed non-invasive study for evaluation of coronary artery disease; however, incidental extracardiac scintigraphic findings observed may provide additional diagnostic information. The authors present the unusual scintigraphic findings in a case of decompensated liver disease with right hepatic hydrothorax, being planned for orthotopic liver transplant.

Evaluation of Staff Radiation Exposure during Transthoracic Echocardiography Close to Myocardial Perfusion Imaging

Transthoracic echocardiography (TTE) and myocardial perfusion imaging (MPI) are used in cardiac patients. In this study the radiation exposure of sonographers performing TTE following MPI was evaluated. Of 40 study patients, 30 underwent same-day 99mTc sestamibi MPI and TTE, while another 10 underwent only TTE. Patients who underwent both studies were divided into three groups: right-handed TTE performed by an echocardiographer and right- and left-handed TTE performed by a cardiac sonographer. Seven thermoluminescent radiation dosimeter badges monitored the forehead, wrists, anterolateral right and left chest, sternal notch, and umbilical region of each examiner. Group characteristics were compared. Radiation exposures were deemed positive if >0.1mSv. There were no statistical differences in patient weight and body mass index. The left-handed approach group had higher residual radioactivity (979±73 vs 884±73 MBq [P<.01] and 906±81 MBq [P<.04]), but no statistical difference in duration of TTE, compared with the other two MPI groups. Radiation exposure was positive in the right anterolateral chest and hand (0.45 and 1mSv, respectively) for the echocardiographer, the right anterolateral chest and wrist and umbilical region (0.59, 1.06, and 0.15mSv, respectively) for the right-handed sonographer, and the left chest and hand (0.12 and 0.34mSv, respectively) for the left-handed sonographer. Dosimeters indicated no radiation exposure in the TTE-only group. Staff members performing TTE after MPI are exposed to radiation that might warrant monitoring. Altering study sequence, adopting a left-handed approach, and using other radiation-reducing techniques can minimize the degree of exposure.

The utility of myocardial perfusion imaging before renal transplantation: a retrospective analysis.

Renal transplantation (RT) reduces morbidity and mortality in patients with end-stage renal failure. Myocardial perfusion imaging provides prognostic information in patients with renal failure, but its role before transplantation remains unclear. We performed a retrospective review assessing the prognostic value of technetium-99m sestamibi myocardial perfusion imaging at a tertiary UK centre. We included scans performed between 2005 and 2012. Available scans were reanalysed to calculate the semiquantitative summed scores: sum rest score (SRS), sum stress score (SSS), sum difference score and sum motion score (SMS). Kaplan-Meier survival estimates assessed all-cause mortality and cardiac events according to scan findings, transplant decision and SSS. Cox-proportional hazards tested for an association between clinical/scan variables and all-cause mortality, and combined all-cause mortality/cardiovascular (CV) events. One hundred and thirty-eight scans were identified with complete follow-up. During a median 40.4-month follow-up, 21 patients died, with 11 nonfatal CV events. There was no significant difference between groups according to scan findings for mortality (log-rank P=0.17) or mortality/CV events (P=0.06). An SSS greater than 8 was associated with higher mortality and CV events combined (P=0.028). An abnormal baseline ECG [hazard ratio (HR): 16.1] and higher SRS (HR: 2.3) were associated independently with higher mortality; an abnormal ECG (HR: 3.4) also predicted higher cardiac events/mortality. Moderate to severe perfusion defects by SSS were associated with higher mortality and CV events. Higher SRS was associated independently with increased mortality on multivariable analysis, highlighting a key role for semiquantitative analysis methods for risk stratification. An abnormal ECG was associated strongly with both endpoints, and may be a useful screening tool to select patients for further investigation.

Inflammatory response to mental stress and mental stress induced myocardial ischemia

BackgroundMental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. MethodsPatients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90 min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. ResultsOf 607 patients analyzed in this study, (mean age 63 ± 9 years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p <0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. ConclusionMental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90 min were significantly associated with MSIMI.

Hemodynamic, catecholamine, vasomotor and vascular responses: Determinants of myocardial ischemia during mental stress

AimsMental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and resultsWe subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (p<0.05 for both), but did not differ in epinephrine, endothelial or macrovascular responses. Only presence of ischemia during conventional stress (OR of 7.1, 95%CI of 4.2, 11.9), high hemodynamic response (OR for RPP response≥vs<ROC cutoff of 1.8, 95%CI of 1.1, 2.8), and high digital vasoconstriction (OR for PAT ratio<vs≥ROC cutoff of 2.1, 95%CI of 1.3, 3.3) were independent predictors of MSIMI. ConclusionIschemia during conventional stress testing and hemodynamic and vasoconstrictive responses to mental stress can help predict subjects with CAD at greater risk of developing MSIMI.

Abstract MP076: Angiographic Coronary Artery Disease Severity and Risk of Mental and Conventional Stress Induced Myocardial Ischemia

Background: Mental stress induced myocardial ischemia (MSIMI) is linked to increased risk of adverse cardiovascular outcomes, but its mechanisms are thought to be different from those of conventional stress-induced ischemia (CSIMI). Specifically, whether MSIMI is associated with more severe underlying obstructive coronary artery disease (CAD) is unclear. We investigated the association between angiographically-defined CAD severity and both MSIMI and CSIMI with a hypothesis that, CAD severity will be linked to CSIMI, but not MSIMI. Methods: A total of 273 patients with stable CAD, aged 51±7 years, 49% female, who survived a myocardial infarction (MI) within the past 8 months (median 167±52 days) were enrolled in the Myocardial Infarction and Mental Stress 2 (MIMS-2) study. The coronary angiogram performed during the index MI hospitalization was used to assess CAD severity. Coronary artery obstruction was assessed by counting the number of diseased vessels with 70% stenosis (DV70%) and using the Gensini Score (GS) after correcting for revascularized vessels. Patients underwent 99mTc sestamibi myocardial perfusion imaging during mental stress, using a public speaking task, and during conventional stress test, using exercise or pharmacological stress. MSIMI and CSIMI were defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. Results: A total of 68 (26%) patients developed CSIMI, while 46 (17%) developed MSIMI. Median DV70% and GS were 0 (0-1), and 3 (0-12), respectively. Using logistic regression models, and after adjustment for age, gender, hypertension, hyperlipidemia and diabetes, obstructive CAD was associated with increased risk of CSIMI [OR(95%CI) of 1.54 (1.02 - 2.31) for DV70% and 1.25 (1.03-1.53), for GS], but not MSIMI [OR(95%CI) of 0.93 (0.56 - 1.53) for DV70%, and 0.94 (0.75-1.18) for GS]. Conclusion: Although CSIMI is linked to underlying coronary obstruction, MSIMI is independent of CAD severity among post- MI patients. Other mechanisms are likely responsible for MSIMI post MI.

Abstract P326: Myocardial Ischemia and Mobilization of Circulating Progenitor Cells

Background: Circulating progenitor cells (CPCs) are involved in vascular repair and regeneration. Low levels of CPCs in patients with CAD have been linked to adverse cardiovascular outcomes. The response of CPCs to transient myocardial ischemia in patients with CAD has not been studied before. We aimed to investigate the CPC response to exercise provoked myocardial ischemia (demand ischemia), and compare it to myocardial ischemia detected during pharmacological stress test (flow mismatch). Methods: 570 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during exercise (69%), or pharmacological stress (31%). myocardial ischemia was defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. CD34+ CPCs were enumerated by flow cytometry at rest and 30 min after stress testing. The change in CPC count was compared between patients with and without myocardial ischemia using mixed linear models. Results: Mean age was 63±9 years, 76% males, 36% with previous myocardial infarction. The incidence of myocardial ischemia was 31% and 41% during exercise and pharmacological stress test, respectively. No difference was observed in resting CPC between patients undergoing exercise vs pharmacological stress test, nor between patients with or without myocardial ischemia. However, patients who developed myocardial ischemia during exercise stress had a significant decrease in CPC with stress in comparison to those without myocardial ischemia (-12% vs 4%, respectively, p=0.006). Furthermore, the change in CPCs was inversely correlated with the magnitude of myocardial ischemia (R=-0.13, p=0.023), suggesting a greater CPC reduction with larger ischemic burden. These findings remained significant even after adjustment for age, gender, race, BMI, previous myocardial infarction, resting levels of CPCs and hematocrit change with stress. No difference was observed in CPC response to pharmacological stress test (change of -1% vs 3%, for patients with and without myocardial ischemia, respectively, p=0.96). Conclusion: Exercise stress-induced myocardial ischemia is associated with a decrease in CPC counts, likely due to increased homing of stem cells to the ischemic myocardium. Whether the extent of CPC uptake has prognostic implication, or whether the CPC response can be altered with intervention needs further investigation.

Correction of hysteretic respiratory motion in SPECT myocardial perfusion imaging: Simulation and patient studies.

Amplitude-based respiratory gating is known to capture the extent of respiratory motion (RM) accurately but results in residual motion in the presence of respiratory hysteresis. In our previous study, we proposed and developed a novel approach to account for respiratory hysteresis by applying the Bouc-Wen (BW) model of hysteresis to external surrogate signals of anterior/posterior motion of the abdomen and chest with respiration. In this work, using simulated and clinical SPECT myocardial perfusion imaging (MPI) studies, we investigate the effects of respiratory hysteresis and evaluate the benefit of correcting it using the proposed BW model in comparison with the abdomen signal typically employed clinically. The MRI navigator data acquired in free-breathing human volunteers were used in the specially modified 4D NCAT phantoms to allow simulating three types of respiratory patterns: monotonic, mild hysteresis, and strong hysteresis with normal myocardial uptake, and perfusion defects in the anterior, lateral, inferior, and septal locations of the mid-ventricular wall. Clinical scans were performed using a Tc-99m sestamibi MPI protocol while recording respiratory signals from thoracic and abdomen regions using a visual tracking system (VTS). The performance of the correction using the respiratory signals was assessed through polar map analysis in phantom and 10 clinical studies selected on the basis of having substantial RM. In phantom studies, simulations illustrating normal myocardial uptake showed significant differences (P<0.001) in the uniformity of the polar maps between the RM uncorrected and corrected. No significant differences were seen in the polar map uniformity across the RM corrections. Studies simulating perfusion defects showed significantly decreased errors (P<0.001) in defect severity and extent for the RM corrected compared to the uncorrected. Only for the strong hysteretic pattern, there was a significant difference (P<0.001) among the RM corrections. The errors in defect severity and extent for the RM correction using abdomen signal were significantly higher compared to that of the BW (severity=-4.0%, P<0.001; extent=-65.4%, P<0.01) and chest (severity=-4.1%, P<0.001; extent=-52.5%, P<0.01) signals. In clinical studies, the quantitative analysis of the polar maps demonstrated qualitative and quantitative but not statistically significant differences (P=0.73) between the correction methods that used the BW signal and the abdominal signal. This study shows that hysteresis in respiration affects the extent of residual motion left in the RM-binned data, which can impact wall uniformity and the visualization of defects. Thus, there appears to be the potential for improved accuracy in reconstruction in the presence of hysteretic RM with the BW model method providing a possible step in the direction of improvement.

Reverse perfusion pattern in myocardial perfusion imaging using technetium-99m-sestamibi in patients with intermediate risk for coronary artery disease in relation to the time of acquisition and intensity of visceral uptake as artifactual causes.

With respect to the equivocal value of the reverse perfusion pattern (RPP) in technetium-99m (Tc)-sestamibi myocardial perfusion imaging, a study was carried out to evaluate this pattern in association with the presence or absence of coronary artery disease (CAD) and other underlying factors, mainly the time of acquisition and the presence of intense visceral uptake. We prospectively studied 102 patients with a moderate risk of CAD (41 men and 61 women, mean age: 56.5±9.2 years) without a previous history of documented CAD, myocardial infarction, or revascularization. Myocardial perfusion imaging was performed using a 2-day dual-phase protocol with the stress and rest images, each obtained 15, 120, and 180 min after an injection of 666-814 MBq Tc-MIBI. According to the time of image acquisition, the following five protocols were defined, A: 15/15 min, B: 15/180 min, C: 180/180 min, D: 180/15 min, and E: 120/120 min for stress/rest images, respectively. The odds of RPP were higher in the cases with more intense infradiaphragmatic visceral uptake on rest-phase images of the protocols A and D (odds ratios=1.2-7.8 and 1.2-7.5, respectively). Our results showed that RPP is related to incorrect normalization. Also, diabetes, sex, and CAD did not correlate with RPP. This study found no relationship between RPP and CAD, diabetes mellitus, and sex; however, an association was found between RPP and incorrect normalization because of the variation of visceral uptake intensity in relation to the time of acquisition at stress and rest phases favoring the artifactual base of this pattern.

Abstract 13388: Autonomic Balance And Mental Stress-induced Myocardial Ischemia

Introduction: Although mental stress-induced myocardial ischemia (MSIMI) has been linked to adverse cardiovascular outcomes, its underlying mechanisms remain to be elucidated. We assessed whether autonomic dysfunction was important in precipitating MSIMI with the hypothesis that autonomic function, estimated using heart rate variability (HRV), will be associated with MSIMI. Methods: We examined autonomic function at rest in 168 patients with CAD using the ANSAR method (ANX 3.0, ANSAR Inc. Philadelphia, PA). Sympathetic and parasympathetic tone were assessed using low (LFa) and respiratory (RFa) frequency HRV that was adjusted for respiration using continuous wavelet transform. Sympathovagal balance was calculated as the ratio of LFa/RFa. Patients underwent 99mTc sestamibi myocardial perfusion imaging during both mental stress testing using a public speaking task, and, as a control condition, with conventional (pharmacologic or exercise) stress testing. Ischemia was defined as a new or worsening impairment in myocardial perfusion within each myocardial segment using a 17-segment model. Results: In our population, (age 63 ± 9 years, 70% men), 11% developed MSIMI and 28% developed conventional stress-induced myocardial ischemia (CSIMI). Patients with MSIMI had higher sympathetic tone and increased sympathovagal balance [median (IQR) LFa of 1.1 (0.4-8.2) vs 0.6 (0.3-1.1) bpm2, p=0.017 and LFa/RFa of 1.7 (0.8-3.6) vs 1.0 (0.6-2.0), p=0.02] but not parasympathetic activity [RFa of 0.8 (0.3-2.9) vs 0.5 (0.2-1.3) bpm2, p=0.29] compared to those without MSIMI. Patients with increased LFa/RFa ratio had significantly higher risk of MSIMI [3rd vs 1st tertile OR(95%CI) of 4.4 (1.1 - 17), p=0.03], that remained significant after adjustment for CAD risk factors, beta blockers, rate pressure product and CSIMI. No correlation was found between LFa, RFa or LFa/RFa HRV and CSIMI. Conclusion: Increased resting sympathovagal balance is associated with increased risk of MSIMI but not CSIMI. This suggests that chronic autonomic imbalance with increased symptathetic tone may be an important factor in the pathogenesis of MSIMI, and may have implications on potential therapies.

Abstract 11582: Vascular, Hemodynamic and Hormonal Response to Mental Stress and Risk of Mental Stress Induced Myocardial Ischemia

Introduction: Mental stress-induced myocardial ischemia (MSIMI) has been linked to adverse cardiovascular outcomes in patients with stable CAD. However, the underlying mechanisms are not well understood. We aimed to study vasomotor, hemodynamic and hormonal responses to mental stress (MS) and their relationships with MSIMI. Methods: 660 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging before, and during a public speaking stressor. Hemodynamic parameters (heart rate, BP, rate-pressure product [RPP]), circulating catecholamines, and peripheral arterial tonometry (PAT, Itamar Inc.) were measured at rest, during, and after MS. MSIMI was defined as myocardial perfusion impairment with MS. Results: Participant age was 63±9; 72% male. Overall, 102 (16.1%) patients developed MSIMI. During MS, there was a significant increase in heart rate, BP, RPP and epinephrine, but not norepinephrine levels. The mean PAT ratio, measured as a ratio of the lowest pulse wave amplitude during the speaking task to the final three minutes of pulse wave amplitude during rest, was 0.7 ± 0.3 indicating vasoconstriction with MS. Patients with MSIMI had a greater hemodynamic response (Figure) and a lower PAT ratio (0.6±0.3 vs 0.7±0.3, p=0.008), in comparison to those with no ischemia. After adjustment for age, CAD risk factors and beta blocker use, both higher hemodynamic response (change in RPP≥median) and more vasoconstriction (PAT ratio&lt;median), but not catecholamine response, were independent predictors of MSIMI [OR(95%CI) of 1.8 (1.1-2.9) and 2 (1.2-3.3), p=0.02 and p=0.01, respectively]. A greater hemodynamic response and a lower PAT ratio had an incremental effect on incidence of MSIMI (Figure). Conclusion: A greater hemodynamic response and peripheral vasoconstriction are associated with MSIMI, indicating that both increased myocardial demand and potentially coronary vasoconstriction contribute to this phenomenon.

Abstract P201: Ischemia with Mental Stress is Associated with Greater Left Ventricular Dyssynchrony

Introduction: Synchronized contraction of left ventricle (LV) is necessary for normal cardiac pump function. Delayed activation of LV segments, known as “dyssynchrony,” can result in systolic and diastolic function deterioration and clinical heart failure. The autonomic nervous system regulates LV conduction and is influenced by psychological stress. We used mental stress testing to examine the effects of psychological stress on LV dyssynchrony and assess whether patients who develop mental stress-induced myocardial ischemia (MSI), a condition associated with doubling of risk for mortality and cardiovascular events, have greater LV dyssynchrony at baseline and/or during stress as compared to MSI negative subjects. We compared results with a control condition of conventional physical (exercise/ pharmacological) stress. Methods: 660 patients with CAD underwent 99mTc[[Unable to Display Character: &amp;#8208;]]sestamibi myocardial perfusion imaging at rest and following both mental and physical stress. Dyssynchrony parameters, measured using the Emory Cardiac Toolbox software, included phase standard deviation (SD) and phase bandwidth; higher levels indicate higher desynchronized contraction. Ischemia with both conditions was blindly assessed by 2 independent readers, with consensus reading for any discordance. The Gensini score was calculated from angiographic data to assess CAD burden. Dyssynchrony data at baseline and during mental/physical stress were log-transformed for analyses. Results: Mean age was 63 years (SD: 9), 180 (27%) were females and 432 (66%) were whites. Overall, 108 (16%) subjects developed mental stress ischemia (MSI+), while 232 (35%) developed physical stress ischemia (PSI+). After adjusting for age, sex, race, traditional CAD risk factors, indicators of CAD burden, history of heart failure, and LV ejection fraction, at baseline MSI+ subjects compared with MSI- had 11% higher phase SD (95% CI: 1% to 19%), and 11% higher phase bandwidth (95% CI: 3% to 20%). PSI+ subjects compared with PSI- had a more modest and non-significant increase in phase SD (mean increase of 4%, 95% CI: -3% to 12%) and phase bandwidth (4%, 95% CI: -3% to 11%). The associations of MSI with baseline dyssynchrony was independent of PSI status. A similar association was noted between MSI and dyssyncrony during mental stress. Among the covariates, male sex (P=0.01), smoking (P=0.02), Gensini score (P=0.01), history of MI (P&lt;0.001), history of heart failure (P&lt;0.001), and LV ejection fraction (P&lt;0.001) were significantly associated with higher baseline dyssynchrony. Conclusion: MSI is associated with greater LV dyssynchrony at rest and during stress. Baseline LV dyssynchrony may be a marker of susceptibility to stress-induced ischemia possibly due to recurrent or chronic subclinical ischemia during daily life. LV dyssynchrony may be a potential mechanism for adverse cardiac events in patients with MSI.

Abstract 17545: Vasoconstriction During Mental Stress Predicts Severity of Mental Stress Induced Myocardial Ischemia

Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. Hypothesis: We hypothesized that increased digital microvascular constriction during both mental stress and recovery are predictive of increased severity of mental stress ischemia. Methods: We evaluated 204 patients with stable CAD with high quality vascular data using a standardized mental stress test using a public speaking task. Peripheral artery tonometry (PAT) (Itamar Inc) was used to assess digital microvascular tone. Vasoconstriction was calculated as the ratio of pulse wave amplitude during speech/recovery and the last 3 minutes of baseline, with lower ratio indicating more vasoconstriction. 99mTc sestamibi myocardial perfusion imaging was performed at rest and with mental stress. A summed difference score (SDS) quantifying severity of reversible perfusion defects (inducible ischemia) comparing rest and stress images was computed using a standard 17-segment model. Four categories of increasing severity were based on cut points of 0, 3, and 6. Results: The mean (SD) age was 64 (8), 16% were women, and 28% were African American. Each category of increase in ischemia severity was associated with a 10% (p=0.04) decrease in speech PAT ratio (Figure) and 11% (p=0.02) decrease in recovery PAT ratio. After multivariable adjustment for sociodemographics, traditional risk factors, medical history, medication use, and psychological risk factors, the associations persisted, with B=-11%, p=0.02 for speech PAT ratio, and B=-8%, p=0.04 for recovery ratio. Conclusion: Peripheral vasoconstriction during mental stress speech as well as recovery predicts MSI severity in a dose-response relationship.

The effect of ivabradine on long term prevention of major adverse cardiac events in acute coronary syndrome using high-sensitivity C-reactive protein level

IntroductionC-reactive protein (CRP) value can identify the risk level for acute coronary syndrome (ACS). Ivabradine, a selective inhibitor of the funny current channel, reduces resting and exercise HR without affecting cardiac contractility or blood pressure. Aim of workEvaluate the influence of Ivabradine on long term prevention of major adverse cardiac events (MACE) using high sensitivity crp (hs CRP). Methodology60 pts were admitted with ACS over the period of 6months. Cardiac enzymes were withdrawn on admission and every 6h thereafter for 24h then followed up daily for five days and when indicated. High sensitivity C-reactive protein (hs-CRP) (quantitative value) which was done on day of admission and repeated for follow up at day 4 and at day 30 patients divided into two groups each 30 pts: group (A) who received conventional therapy & ivabradine, group (B) who received conventional therapy only. Ivabradine given within 48h of admission 5mg twice daily upgraded to 7.5mg twice daily after one week if tolerable Myocardial perfusion imaging (MPI): Patients were subjected to Technetium99 sesta MIBI Myocardial perfusion imaging (MPI) within 6–8h after admission and were followed up on day 30 with the same dose of injection using multi-spect Siemens dual head gamma Camera. ResultsThere were significant variances in Hs-CRP value at day 30 in both groups (P value<0.001). Patients of group A showed statistically significant lower level of hs-CRP at day 30 compared to group B (0.7±0.3mg/dl versus 1.66±0.9mg/dl; P value<0.001) but there was no statistically significant difference between both groups regarding 30days follow up MACE (P value 0.552). ConclusionAdministration of ivabradine within 48h of CCU admission decreased hs-CRP level in patients with acute coronary syndrome (unstable angina) but did not decrease the occurrence of major cardiac events in ACS patients.