Stress-induced Ischemia Research Articles

TRANSIENT ISCHEMIC DILATION: A NEW PERSPECTIVE UTILIZING CARDIAC MRI

Stress-induced global LV myocardial ischemia is difficult to detect by nuclear myocardial perfusion imaging (MPI). Digital LV volume software is used to assess changes in overall scintigraphic LV volume after stress, and is termed transient ischemic dilation(TID). The mechanism of TID is thought to

Angina and mental stress-induced myocardial ischemia

ObjectiveMental stress-induced myocardial ischemia is a common phenomenon in patients with coronary artery disease (CAD) and an emerging prognostic factor. Mental stress ischemia is correlated with ambulatory ischemia. However, whether it is related to angina symptoms during daily life has not been examined. MethodsWe assessed angina frequency (past month) in 98 post-myocardial infarction (MI) subjects (age 18–60years) using the Seattle Angina Questionnaire. Patients underwent [99mTc]sestamibi SPECT perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. ResultsThe mean age was 50years, 50% were female and 60% were non-white. After adjustment for age, sex, smoking, CAD severity, depressive, anger, and anxiety symptoms, each 1-point increase in mental stress–SDS was associated with 1.73-unit increase in the angina frequency score (95% CI: 0.09–3.37) and 17% higher odds of being in a higher angina frequency category (OR: 1.17, 95% CI: 1.00–1.38). Depressive symptoms were associated with 12% higher odds of being in a higher angina frequency category (OR: 1.12, 95% CI: 1.03–1.21). In contrast, exercise/pharmacological stress-induced SDS was not associated with angina frequency. ConclusionAmong young and middle-aged post-MI patients, myocardial ischemia induced by mental stress in the lab, but not by exercise/pharmacological stress, is associated with higher frequency of retrospectively reported angina during the day. Psychosocial stressors related to mental stress ischemia may be important contributory factor to daily angina.

Clinical intervention research on mental stress-induced myocardial ischemia

To observe the impact of Xinkeshu on top of standard medication on psychological stress-related emotional and biophysiological parameters in patients with mental stress-induced myocardial ischemia (MSIMI). A randomized controlled clinical trial was conducted on 40 patients with MSIMI and patients were randomized into treatment group (n = 21) and control group (n = 19) by random number table method. Patients in the treatment group received Xinkeshu (12 capsules/d) on top of standard therapy, and the control group received placebo on top of standard therapy. Serum homocysteine (Hcy), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were compared between the groups at baseline and after 8 weeks therapy. (1) Baseline data were similar between the 2 groups (all P > 0.05). (2) After 8 weeks, LVFS was significantly increased (from (34.62 ± 5.76)% to (35.90 ± 4.99) %, P = 0.027) and serum Hcy (from (18.08 ± 1.81) µmol/L to (16.06 ± 10.10) µmol/L), PHQ-9 (from 8.14 ± 3.98 to 6.28 ± 2.87) and GAD-7 (from 9.52 ± 4.98 to 6.48 ± 3.84) were significantly reduced in treatment group (all P < 0.05) compared to baseline. In the control group, only GAD-7 was significantly reduced (from 8.89 ± 5.06 to 6.74 ± 4.80, P = 0.003) after 8 weeks therapy compared to baseline (P < 0.05) while other parameters remained unchanged (all P > 0.05). Xinkeshu on the top of standard therapy can improve the emotional state and left ventricular systolic function in patients with MSIMI.

Mechanisms of QRS voltage changes on ECG of healthy subjects during the exercise test

Electrocardiography is the most commonly used technique for detection stress-induced myocardial ischemia. However, the sensitivity of ECG-criteria is not high. One of the major problem is the difficulty in differentiating ECG changes caused by various factors. The aim of this study was to evaluate the dependence of the QRS voltage changes during exercise on parameters of central hemodynamics, gender particularities and to reveal mechanisms causing these changes. To eliminate the effect of changes in cardiomyocytes transmembrane potentials under the influence of the neurotransmitters of the autonomic nervous system during stepwise increasing exercises and/or due to a lack of ATP results from inadequate myocardial blood flow only healthy subjects not older than 35 years were included in the study (7 men and 7 women) and only periods of ventricular depolarization (QRS complex on the ECG) were included in the analysis. We compared the changes of QRS waves during exercise sessions with two upper and one lower limbs in both men and women. The exercise load was twice bigger in exercise with one leg relative to exercise with two arms. Responses of heart rate and systolic arterial pressure were similar. Amplitude of S-wave in left chest leads significantly increased in both sessions without significant difference between augmentations in the sessions and in groups of men and women. Significant relationship between the S wave augmentation and the peak systolic arterial pressure were revealed. Furthermore, the QRS changes during the exercise with vertical and a horizontal torso position were compared to assess the impact of diastolic arterial pressure and displacement of the diaphragm and heart rotation due to increase of abdominal pressure during the last steps of exercise. The obtained results allow us to exclude the impact of the heart position and size changes, as well as the exercise load on S-wave changes and make a conclusion about the dependence of this parameter on the value of systolic blood pressure.

Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study

BACKGROUNDMental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity.METHODSEligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT (Responses of Myocardial Ischemia to Escitalopram Treatment) study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression.RESULTSOf the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation, 43.33% (N=117) met criteria for MSIMI and 18.15% (N=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10 μM (6.95[5.54] vs. −14.23[8.75].; p=0.045), epinephrine 10 μM (12.84[4.84] vs. −6.40[7.61].; p=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. −27.34[8.34]; p < .001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups.CONCLUSIONSThese findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD.

Ischaemia-Driven Optimal Therapeutic Approach in Asymptomatic Patients with High Cardiovascular Risk: The Value of Clinical, Laboratory and Myocardial Spect Imaging Findings

We wanted to evaluate the presense of myocardial ischaemia in asymptomatic patients with high cardiovascular risk, the influencing clinical and laboratory factors and the impact of ischaemia on final management decision. We evaluated 60 asymptomatic patients with high CV risk, who underwent SPECT myocardial perfusion imaging (MPI) for detection of suspected CAD. We used the 17 segment model for quantitative and semiquantitative scan perfusion and function analysis using perfusion scores. All patients had full blood laboratory analyses including lipid values, presence of albuminuria, rest and stress ECG. Logistic regression analysis was used to assess the impact of clinical and laboratory parameters on myocardial ischaemia prevalence. Stress-inducible ischaemia was found in 19 pts (33%), fixed defects were found in 13% and mixed defects in 9% of cases. The average ischaemia amount was 10%. Mild ischaemia was found in 12 patients (64%)--summed stress score (SDS)<4, moderate ischaemia in 5 patients (26%)--SDS 5-7 and severely abnormal scans in 2 patients (10%)--SDS>7. Severe ischaemia was only related to the duration of diabetes. Six pts with severe ischaemia had ST depression>2 mm on stress study, and a higher wall motion index and LVEF fall>5% during stress study (p<0.01). Stepwise logistic regression analysis for prediction of stress-induced ischaemia showed OR 2.4 (95% CI 1.7-3.6) for stress-induced ECG changes and OR 3.9 for presence of DM over 10 y (95% CI 2.3-6.6). Seven patients with ischaemia>10%, were referred for coronary angiography. MPI is a valuable method for preclinical assessment of myocardial ischaemia in patients with high CV risk, which can improve prognosis and guide treatment decision.

Relationship between myocardial perfusion abnormalities and contractile impairment in anginal patients

BackgroundA relationship between left ventricular (LV) contractile impairment and myocardial perfusion abnormalities has been suggested. Methods and ResultsThree-hundred and thirty-seven patients underwent myocardial perfusion imaging at CZT and coronary angiography. On scintigraphic images, the summed difference score (SDS) and LV-ejection fraction (EF) were computed. Patients were categorized as follows: Group-1 (LV-EF < 40%; 71 patients), Group-2 (LV-EF ≥ 40% and < 55%; 77 patients), and Group-3 (LV-EF ≥ 55%; 189 patients). Significant coronary artery disease (CAD; ≥50% stenosis) was recognized in 159/337 (47%) patients. Interestingly, while in Group-3 subjects an inverse relationship between SDS values and post-stress LV-EF was evident (P < .001), Group-1 patients presented a significant association between an increased SDS and more elevated post-stress LV-EF values (P = .009). Similarly, despite in the overall population an increasing severity of CAD was associated with higher SDS values (P < .001), this relationship disappeared in Group-1 patients (P = .298). At multiple regression analysis, after correction for CAD, LV dysfunction was negatively associated with an elevated SDS (P = .018). Conversely in patients with normal LV function and no history of myocardial infarction, CAD extent, and functional measures of stress-induced myocardial ischemia were strictly correlated. ConclusionsIndependently from CAD, a significantly impaired LV function associates with a lower prevalence of reversible ischemia.

Abstract 9789: Transient Elevation of Highly Sensitive Troponin T Levels in Patients With Documented Coronary Artery Disease Following Stress Myocardial Perfusion Imaging

Introduction: Cardiac troponins are the preferred biomarkers of myocardial injury. More sensitive assays led to the detection of circulating troponins not only in myocardial infarction, but also in apparently healthy subjects after prolonged exercise. Hypothesis: In the era of highly sensitive troponin T (hs-TnT) tests we assesed the hypothesis that brief but intense exercise during diagnostic tests might cause elevated troponin levels in patients with stable coronary artery disease (CAD). Methods: Seventy-two patients (71% male, age 64±10 years) with documented CAD, LVEF &gt;45%, normal renal function and normal baseline hs-TnT levels (&lt;14 ng/l) underwent myocardial perfusion imaging (MPI, Tc-99m sestamibi) using bicycle stress test (n=19) or adenosine stimulation (n=55). Hs-TnT levels were detected immediately before and immediately after stress, and again after 4 hours and 24 hours. The extent of stress-induced myocardial ischemia was estimated from perfusion scores derived from single-photon emission computed tomography (SPECT) post stress and rest images. Significant reversible myocardial ischemia was prospectively defined as regional perfusion abnormality ≥10% of the left ventricular myocardium. Results: Transient elevations of hs-TnT levels above the normal limit occurred in 5/72 patients (7%) after diagnostic stress testing with a peak level at 4 hours after stress. Hs-TnT elevations were more common in patients with stress-induced myocardial ischemia (3/12, 25%) compared to patients without ischemia (2/60, 3%; p=0.038). However, no relation between peak hs-TnT levels and the extent of reversible myocardial ischemia was found (r=-0.16, n=72, p=NS). Furthermore, peak hs-TnT levels were similar with both types of stress (bicycle 6.6 [4.0 – 10.5] pg/l versus adenosine 5.1 [3.1 – 8.6] pg/l, median [IQR]). Conclusions: Transient hs-TnT elevations are quite common after diagnostic stress testing and occur more frequently in patients with documented reversible ischemia. No relation between peak hs-TnT levels and the extent of reversible myocardial ischemia at MPI was obtained. In conclusion this suggests that hs-TNT elevation during stress testing depends on other factors then those leading to SPECT-detected myocardial ischemia.

Semi-supine exercise stress echocardiography in children and adolescents: feasibility and safety.

Although exercise stress echocardiography (ESE) is a well-validated technique in adult population, its use in children is quite limited. We aimed to assess the feasibility, the safety and the reproducibility of ESE, using on-line scanning in semi-supine cyclo-ergometer protocol in a large pediatric population. Between July 2008 and January 2013, 42 patients (mean age 14 ± 3) were evaluated with a bicycle ESE performing 50 studies. ESE was successfully performed and well tolerated by all patients. None of the patients presented with adverse effects of stress-induced ischemia. HR was 82 ± 13 at rest, and 153 ± 19.1 during peak exercise. Among 544 views analyzed for grading of image quality, the visualization was optimal in 473 (87 %), suboptimal in 39, and inadequate in 32 (6 %). 37 tests were performed in patients with congenital or acquired coronary abnormality. Regional wall motion abnormalities (RWMA) were revealed in nine cases (24 %). The agreement between the two different observers showed a K index of 0.7276 (95 % CI 0.6497–0.8055) for the image quality and a K index of 0.5125 (95 % CI 0.4782–0.5468) for the RWMA analysis. Among ten patients with hypertrophic cardiomyopathy, we were able to demonstrate the new comparison of significant left ventricular outflow tract gradient (≥30 mmHg) during exercise in three patients (30 %). Bicycle stress echocardiography performed by on-line scanning during exercise is a feasible, safe, and reproducible modality in children. Further data to assess its diagnostic accuracy are, however, needed. Stress echocardiography provides a dynamic assessment of the myocardial structure and function under conditions of physiologic or pharmacologic stress.

Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study.

Although emotional stress is associated with ischemic heart disease (IHD) and related clinical events, sex-specific differences in the psychobiological response to mental stress have not been clearly identified. We aimed to study the differential psychological and cardiovascular responses to mental stress between male and female patients with stable IHD. Patients with stable IHD enrolled in the REMIT (Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram) study underwent psychometric assessments, transthoracic echocardiography, and platelet aggregation studies at baseline and after 3 mental stress tasks. Mental stress-induced myocardial ischemia (MSIMI) was defined as the development or worsening of regional wall motion abnormality, reduction of left ventricular ejection fraction (LVEF) ≥8% by transthoracic echocardiography, and/or ischemic ST-segment change on electrocardiogram during 1 or more of the 3 mental stress tasks. In the 310 participants with known IHD (18% women, 82% men), most baseline characteristics were similar between women and men (including heart rate, blood pressure, and LVEF), although women were more likely to be nonwhite, living alone (p < 0.001), and unmarried (p < 0.001); they also had higher baseline depression and anxiety (p < 0.05). At rest, women had heightened platelet aggregation responses to serotonin (p = 0.007) and epinephrine (p = 0.004) compared with men. Following mental stress, women had more MSIMI (57% vs. 41%; p < 0.04), expressed more negative (p = 0.02) and less positive emotion (p < 0.001), and demonstrated higher collagen-stimulated platelet aggregation responses (p = 0.04) than men. Men were more likely than women to show changes in traditional physiological measures, such as blood pressure (p < 0.05) and double product. In this exploratory analysis, we identified clear, measurable, and differential responses to mental stress in women and men. Further studies should test the association of sex differences in cardiovascular and platelet reactivity in response to mental stress and long-term outcomes. (Responses of Myocardial Ischemia to Escitalopram Treatment [REMIT]; NCT00574847).

Association between anger and mental stress–induced myocardial ischemia

Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. [(99m)Tc]-sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task) and after exercise/pharmacologic stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed-difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. The mean age was 50 years, 50% were female, and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive, and anxiety symptoms, each IQR increment in state-anger score was associated with 0.36 U-adjusted increase in ischemia as measured by the summed-difference score (95% CI 0.14-0.59); the corresponding association for trait anger was 0.95 (95% CI 0.21-1.69). Anger expression scales were not associated with ischemia. None of the anger dimensions was related to ischemia during exercise/pharmacologic stress. Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress but not during exercise/pharmacologic stress. Patients with this psychologic profile may be at increased risk for silent ischemia induced by emotional stress, and this may translate into worse prognosis.

Metabolomics analysis reveals insights into biochemical mechanisms of mental stress-induced left ventricular dysfunction.

Mental stress induced left ventricular dysfunction (LVD) has been associated with a greater risk of adverse events in coronary heart disease (CHD) patients independent of conventional risk indicators. The underlying biochemical mechanisms of this cardiovascular condition are poorly understood. Our objective was to use metabolomics technology to identify biochemical changes that co-occur with mental stress-induced LVD in patients with clinically stable CHD. Participants were adult CHD patients who were recruited for mental stress-induced myocardial ischemia screening. For this study, we randomly selected 30 patients representing the extremes of the mental stress-induced left ventricular ejection fraction (LVEF) change distribution; 15 who showed LVD (i.e. LVEF reduction ≥5) and 15 who showed a normal left ventricular response (NLVR; i.e. a LVEF increase of ≥5) to three mental stressors. An electrochemistry based metabolomics platform was used to profile pre- and post-stress serum samples yielding data for 22 known compounds, primarily within the tyrosine, tryptophan, purine and methionine pathways. There were significant stress-induced changes in several compounds. A comparison between the NLVR and LVD groups showed significant effects for kynurenine (p = .036, N-acetylserotonin (p = .054), uric acid (p = .015), tyrosine (p = .019) and a trend for methionine (p = .065); the NLVR group showed a significantly greater stress-induced reduction in all of those compounds compared to the LVD group. Many of these biochemicals have been implicated in other stress-related phenomena and are plausible candidates for mechanisms underlying LVD in response to mental stress.

Association of vitamin D status with mental stress-induced myocardial ischemia in patients with coronary artery disease.

Mental stress-induced (MSIMI) or physical stress-induced (PSIMI) myocardial ischemia portends a worse prognosis in patients with coronary artery disease (CAD). Vitamin D insufficiency is associated with adverse cardiovascular outcomes, but its relationship to myocardial ischemia remains unclear. We hypothesized that vitamin D insufficiency will be associated with a higher prevalence of myocardial ischemia in patients with CAD. In 255 patients with stable CAD, myocardial perfusion imaging was performed to assess ischemia in response to mental and physical stress protocols. Vitamin D insufficiency was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 30 ng/ml, collected on the day of stress testing. Mean (standard deviation) 25(OH)D level was 30.8 (12.8) ng/ml, and 139 (55%) patients had vitamin D insufficiency. MSIMI occurred in 30 (12%) patients and PSIMI in 67 (27%). Individuals with MSIMI had significantly lower levels of 25(OH)D as compared with those without MSIMI (24.0 [8.6] versus 31.7 [12.9], p = .002). The prevalence of MSIMI was higher in those with as compared with those without vitamin D insufficiency (17% versus 6%, p = .009). Moreover, low 25(OH)D levels remained independently associated with MSIMI after adjusting for potential confounders. Conversely, 25(OH)D levels were similar between those with or without PSIMI (29.8 [13.0] versus 31.4 [12.7], p = .37), as was the prevalence of PSIMI in those with or without vitamin D insufficiency (29% versus 24%, p = .42). Vitamin D insufficiency is associated with a higher prevalence of MSIMI but not PSIMI among stable patients with CAD. Whether this association serves as a potential mechanism linking low vitamin D status to adverse cardiovascular outcomes warrants further investigation.

Relevance of early poststress variation in left ventricular function studied by gated-SPECT: evaluation in different clinical settings and relationship with angiography results.

Stress-induced ischemia may cause a decrease in left ventricular ejection fraction (EF). We evaluated the variation in early postexercise EF (S-EF) compared with rest EF (R-EF) in different clinical settings to detect ventricular dysfunction. We also correlated ventricular dysfunction with an angiographic score, the Syntax score, in a subgroup of ischemic patients. Gated-SPECT images were acquired 12 min after exercise stress and at rest in 1481 patients. Patients were classified as controls, negative for ischemia, mildly ischemic, moderately/severely ischemic, necrotic, and necrotic with ischemia. Mean end-diastolic volume, end-systolic volume, and EF were compared in each group. The ratio between stress to rest EF was indicated as the functional score. Angiography results were collected for 55% of moderately/severely ischemic patients. Sixty-one angiographies were also completed with Syntax score evaluation. In negative, necrotic, and mildly ischemic patients no differences were found between S-EF and R-EF. An opposite trend was observed in moderately/severely ischemic patients with a decrement of S-EF compared with R-EF (54.80±11.33 vs. 57.79±11.14; P<0.0001). Coronary artery disease was confirmed by angiography in 93% of moderately/severely ischemic patients. In 61 patients who underwent Syntax score evaluation, significant correlation was observed with functional score. Significant decrease in functional score was found in patients with coronary artery bypass graft indication compared with patients with percutaneous coronary intervention or medical indication. Early poststress gated-SPECT acquisition allows the detection of ventricular dysfunction in moderately/severely ischemic disease and provides additional information when directing patients to angiography and revascularization.

Congruity between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients

Congruity between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients

Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET.

Absolute quantitation of myocardial blood flow (MBF) by PET is an established method of analyzing coronary artery disease (CAD) but subject to the various shortcomings of available radiotracers. Flurpiridaz F 18 is a novel PET radiotracer that exhibits properties of an ideal tracer. A new absolute perfusion quantitation method with flurpiridaz was developed, taking advantage of the early kinetics and high first-pass extraction by the myocardium of this radiotracer, and the first-in-human measurements of MBF performed in 7 healthy subjects and 8 patients with documented CAD. PET images with time-activity curves were acquired at rest and during adenosine stress. In healthy subjects, regional MBF between coronary artery territories did not differ significantly, leading to a mean global MBF of 0.73 mL/min/g at rest and 2.53 mL/min/g during stress, with a mean global myocardial flow reserve (MFR) of 3.70. CAD vascular territories with <50% stenosis demonstrated a mean MBF of 0.73 at rest and 2.02 during stress, leading to a mean MFR of 2.97. CAD vascular territories with ≥50% stenosis exhibited a mean MBF of 0.86 at rest and 1.43 during stress, leading to a mean MFR of 1.86. Differences in stress MBF and MFR between normal and CAD territories, as well as between <50% and ≥50% stenosis vascular territories, were significant (P < 0.01). Absolute quantitation of MBF in humans with the novel PET radiotracer flurpiridaz is feasible over a wide range of cardiac flow in the presence or absence of stress-inducible myocardial ischemia. The significant decrease in stress MBF and ensuing MFR in CAD territories allows a clear distinction between vascular territories exhibiting stress-inducible myocardial ischemia and those with normal perfusion.

Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

ObjectivesDepression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.MethodsWe studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.ResultsThere was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.ConclusionAmong young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress.

A functional genetic variant in the microsomal triglyceride transfer protein is associated with cardiac dysfunction during stress-induced ischemia

A functional genetic variant in the microsomal triglyceride transfer protein is associated with cardiac dysfunction during stress-induced ischemia

Predictors of response to intramyocardial bone marrow cell treatment in patients with refractory angina and chronic myocardial ischemia

BackgroundWe previously showed that intramyocardial bone marrow cell (BMC) injection in patients with refractory angina and chronic myocardial ischemia improves myocardial perfusion, cardiac function and disease-related complaints. Treatment effect varied between patients, but the predictors of response remain to be identified. Therefore, the aim of the present study was to assess whether patient characteristics, procedural data and baseline measurements influence the response to intramyocardial BMC treatment in a large cohort of refractory angina patients. Methods and resultsIn 120 patients (64±9years, 88% men) with refractory angina, 97±13×106 BMCs were injected intramyocardially in regions with stress-inducible ischemia as assessed by single photon emission computed tomography (SPECT). Canadian Cardiovascular Society angina (CCS) class, quality-of-life score, exercise testing, SPECT and magnetic resonance imaging were performed at baseline and at 3months follow-up demonstrating significant improvements in CCS class, quality-of-life, exercise capacity, myocardial perfusion and left ventricular function (all variables P<0.001). Multivariate analysis was performed to evaluate the influence of patient characteristics, procedural data and baseline measurements on BMC treatment response. Based on the improvement of myocardial perfusion at stress, diabetes and a large number of ischemic segments at baseline were shown to be independently associated with a large response to BMC therapy. ConclusionThe present study demonstrates that diabetes and a large number of ischemic segments are predictors of a large response to intramyocardial BMC injection in refractory angina and chronic ischemia. Furthermore, the safety and efficacy results of previous trials are now confirmed in a larger study population.

Validation of an automated method to quantify stress-induced ischemia and infarction in rest-stress myocardial perfusion SPECT

BackgroundMyocardial perfusion SPECT (MPS) is one of the frequently used methods for quantification of perfusion defects in patients with known or suspected coronary artery disease. This article describes open access software for automated quantification in MPS of stress-induced ischemia and infarction and provides phantom and in vivo validation. Methods and ResultsA total of 492 patients with known or suspected coronary artery disease underwent both stress and rest MPS. The proposed perfusion analysis algorithm (Segment) was trained in 140 patients and validated in the remaining 352 patients using visual scoring in MPS by an expert reader as reference standard. Furthermore, validation was performed with simulated perfusion defects in an anthropomorphic computer model. Total perfusion deficit (TPD, range 0-100), including both extent and severity of the perfusion defect, was used as the global measurement of the perfusion defects. Mean bias ± SD between TPD by Segment and the simulated TPD was 3.6 ± 3.8 (R2 = 0.92). Mean bias ± SD between TPD by Segment and the visual scoring in the patients was 1.2 ± 2.9 (R2 = 0.64) for stress-induced ischemia and −0.3 ± 3.1 (R2 = 0.86) for infarction. ConclusionThe proposed algorithm can detect and quantify perfusion defects in MPS with good agreement to expert readers and to simulated values in a computer phantom.