BACKGROUND:Coronary microvascular dysfunction (CMD) is associated with a poor prognosis but is difficult to diagnose non-invasively. In a recent paper, ST-segment depression on exercise-ECG was found to have a very high positive predictive value (PPV) for CMD in a highly selected group of patients. OBJECTIVES:In the present study of chest pain patients, we used myocardial perfusion single photon emission CT (MPS) to rule out ischaemia due to epicardial coronary stenosis. In the remaining patients with suspected CMD, we studied the prognostic value of ex-ECG findings. METHODS:A single-centre observational study of 1021 consecutive patients examined with MPS and ex-ECG. Follow-up data were acquired from national registries. Major adverse cardiac events (MACE) were defined as cardiovascular death, myocardial infarction, unstable angina and unplanned revascularisation. A total of 113 patients were excluded due to inconclusive ex-ECG findings or missing data, and 148 due to ischaemia on MPS. RESULTS:In the final study cohort (n=760) with a mean age of 63 years and 55% female, ex-ECG was abnormal in 126 patients (17%). During a mean follow-up of 8.5 years, MACE occurred in 31 (25%) patients with abnormal ex-ECG and 103 (16%) patients with normal ex-ECG. The Kaplan-Meier curves for cumulative events separated significantly (log-rank p=0.01), but when adjusting for age, sex, comorbidities and exercise capacity, abnormal ex-ECG was no longer significantly associated with MACE (HR 1.1, CI 0.7 to 1.7, p=0.6). The prognostic PPV of an abnormal ex-ECG was only 25% (31/126) and this decreased to 17% (11/66) when excluding patients with known coronary artery disease (n=323). CONCLUSIONS:In patients with suspected CMD, ischaemic ST-segment changes are of limited prognostic value, showing poor sensitivity and low PPV for the occurrence of MACE. However, reduced exercise capacity was an independent risk factor and, therefore, ex-ECG testing could be considered if a functional assessment of patients is warranted.

BACKGROUND:Myocardial perfusion SPECT (MPS) and exercise electrocardiography (Ex-ECG) results are of prognostic importance for short-term follow up duration. However, the value of MPS or Ex-ECG findings for long-term risk assessment is less evident as underlying risk factors for ischemic heart disease (IHD) gain in importance. OBJECTIVES:To assess the short- and long-term prognostic value of MPS and Ex-ECG in relation to known risk factors. METHODS AND MATERIALS:An observational study of 908 patients (age 63 years, 49% male, 45% prior IHD) referred for MPS and Ex-ECG. Follow-up was divided into two periods (short-term: <5 years and long-term: >5 years). Cardiac events were defined as a composite of acute myocardial infarction, unstable angina, unplanned revascularization and cardiovascular death. RESULTS:The composite endpoint occurred in 95 patients (short-term follow up) and in 94 patients (long-term follow up). In multivariable models stress testing had a strong predictive value for short-term follow up (HR for MPS = 2.9, CI = 1.9-4.5, p < 0.001 and HR for Ex-ECG = 2.1, CI 1.3-3.3, p = 0.002), but no predictive value for long-term follow up (HR for MPS = 0.9, CI = 0.5-1.5, p = 0.70 and HR for Ex-ECG = 1.0, CI = 0.6-1.6, p = 0.92). Male sex and prior IHD were significant predictors regardless of follow up duration. Age, diabetes and decreased exercise capacity were risk factors for long-term follow up. CONCLUSIONS:The prognostic value of MPS and Ex-ECG results are strong for short-term follow up but diminish over time and do not contribute significantly in multivariable models after 5 years. Long-term prognosis is primarily governed by underlying risk factors and exercise capacity.

Background Both myocardial perfusion single‐photon emission computed tomography (MPS) and exercise ECG (Ex‐ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex‐ECG improves risk prediction. Current guidelines no longer recommend Ex‐ECG for diagnostic evaluation of chronic coronary syndrome, but Ex‐ECG could still be of incremental prognostic importance. Methods and Results This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex‐ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex‐ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS−/Ex‐ECG+, n=126 and MPS+/Ex‐ECG−, n=76). During follow‐up, 95 events occurred. Annualized event rates significantly increased across groups (MPS−/Ex‐ECG− =1.3%, MPS−/Ex‐ECG+ =3.0%, MPS+/Ex‐ECG− =5.1% and MPS+/Ex‐ECG+ =8.0%). In multivariable analyses MPS was the strongest predictor regardless of Ex‐ECG findings (MPS+/Ex‐ECG−, hazard ratio [HR], 3.0, P=0.001 or MPS+/Ex‐ECG+, HR,4.0, P<0.001). However, an abnormal Ex‐ECG almost doubled the risk in subjects with normal MPS (MPS−/Ex‐ECG+, HR, 1.9, P=0.04). Conclusions In patients with chronic coronary syndrome, combining the results from MPS and Ex‐ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex‐ECG to MPS, especially in patients with normal MPS.

Abstract Background Abnormal results of myocardial perfusion SPECT (MPS) or exercise ECG (Ex-ECG) is known to be associated with increased risk of ischemic cardiac events. The predictive value of stress testing however, is influenced by underlying risk factors as well as follow up duration and may vary considerably over time. With traditional Cox proportional hazards analysis the time-varying effects are not sufficiently accounted for. Purpose To evaluate the prognostic longevity of MPS and Ex-ECG using statistical methods that allow hazard ratio changes over time. Methods 908 patients (age 63 years, 49% male, 45% prior ischemic heart disease (IHD)) referred for MPS were prospectively included. Ex-ECG was performed in conjunction with MPS. Registry data were used for follow up. The outcome was a composite of acute myocardial infarction, unstable angina, unplanned revascularization, and cardiovascular death. Cox proportional hazard analysis and smoothed hazard functions with splines were used for risk assessment during follow up. Results Ex-ECG or MPS were abnormal in 198 (22%) or 148 (16%) of patients respectively. The mean follow up time was 8.2±2.6 years and the composite end point was reached in 189 patients (21%). The Kaplan-Meier curves suggest an interaction with time with the risk of event for subjects with abnormal test results being highest in the 2-3 of years after which the curves are approximately parallel (Figure 1). In multivariable models the best fit (lowest Akaike information criterion (AIC) value) was obtained with a logarithmic interaction term for time. With this approach and controlling for known risk factors the hazard ratio (HR) drops to 1 after approximately four years for both Ex-ECG and MPS (Figure 2). Age (HR=1.04, p<0.001), sex (HR=2.0, p<0.001), IHD (HR=1.7, p<0.001) and reduced exercise capacity (HR=0.99, p<0.001) were independent significant predictors of risk. Conclusions The high risk associated with abnormal MPS and Ex-ECG results decrease rapidly over time and after approximately 4 years the predictive value is lost. Thus, the long-term impact on prognosis of stress testing appear questionable. The time-varying effects on risk are substantial and warrant statistical considerations when designing clinical follow up studies of chronic coronary syndrome.

We investigated if uptake pattern on myocardial perfusion SPECT (MPS) in patients with left bundle branch block (LBBB) is related to myocardial fibrosis, myocardial wall motion, and electrocardiography (ECG) characteristics. Twenty-three patients (9 women) with LBBB, examined with MPS and cardiac magnetic resonance (CMR), were included. Tracer uptake on MPS was classified by visual interpretation as typical LBBB pattern (Defect+, n = 13) or not (Defect−, n = 10) and quantitatively. CMR images were evaluated for wall thickness and for myocardial wall motion both by visual assessment and by regional myocardial radial strain from feature tracking, and for presence and location of myocardial fibrosis. ECGs were analyzed regarding QRS duration and the presence of strict criteria for LBBB. Wall thickness was slightly lower in the septum compared to the lateral wall in Defect+ patients (5.6 ± 1.1 vs 6.0 ± 1.3 mm, P = 0.03) but not in Defect− patients (5.6 ± 1.0 vs 5.6 ± 0.9 mm, P = 0.84). Defect+ patients showed a larger proportion of dyskinetic segments in the septum and hyperkinetic segments in the lateral wall compared to Defect− patients (P = 0.006 and P = 0.004, respectively). Decreased myocardial radial strain was associated with decreased tracer uptake by MPS (R = 0.37, P < 0.001). Areas of fibrosis did not match areas with uptake defect on MPS. No differences in ECG variables were seen. The heterogeneous regional tracer uptake in some patients with LBBB is related to underlying regional myocardial dyskinesia, wall thickening, and wall thickness rather than stress-induced ischemia, myocardial fibrosis, or specific ECG characteristics.

Summary Background This retrospective study aimed to determine the diagnostic performance of exercise‐induced ST response in relation to findings by myocardial perfusion single photon emission computed tomography ( MPS ), with focus on gender differences, in patients with suspected or established stable ischemic heart disease. Methods MPS findings of 1 021 patients (518 females) were related to the exercise‐induced ST response alone (blinded and unblinded to gender) and ST response together with additional exercise stress test ( EST ) variables (exercise capacity, blood pressure and heart rate response). Results Exercise‐induced ischaemia by MPS was found in 9% of females and 23% of males. Diagnostic performance of exercise‐induced ST response in relation to MPS findings in females versus males was: sensitivity = 48%,70%; specificity = 67%, 64%; PPV = 13%, 38%; NPV = 93%, 87%. Adding more EST variables to the ST response interpretation yielded in females vs males: sensitivity = 44%, 51%; specificity = 84%, 83%; PPV = 22%, 48% and NPV = 93%, 85%. Conclusions In patients who have performed EST in conjunction with MPS , there is a gender difference in the diagnostic performance of ST response at stress, with a significantly lower PPV in females compared to males. For both genders, specificity can be significantly improved, and a higher PPV can be obtained, while the sensitivity might be compromised by considering more EST variables, in addition to the ST response.

Background: Evaluation of stress-induced ST deviations constitutes a central part when interpreting the findings from an exercise test. The aim of this analysis was to assess the pathophysiologic correlate of stress-induced ST elevation and ST depression with regard to presence, amount and location of myocardial ischemia as assessed by myocardial perfusion SPECT, (MPS) in patients with suspected coronary artery disease.Methods and results: 226 patients who had undergone bicycle stress test in conjunction with MPS were included. Of these, 198 were consecutive patients while 28 patients were included on the basis of having stress-induced ST elevation mentioned in their clinical report. The amount and location of ST changes were related to MPS finding. Summed stress scores (SSS) from MPS images were used to measure the amount of stress-induced ischemia. The positive predictive values for detecting stress-induced ischemia were 28% for the consecutive patients with ST depression and 75% for patients with ST elevation. The maximum and sum of stress-induced ST elevations correlated with SSS (r(2)=0.58, p<0.001 and r(2)=0.73, p < 0.001), whereas the maximum and sum of significant ST depressions did not (r(2)=0.022, p=0.08 and r(2)=0.024, p = 0.10). The location of ST elevation corresponded to the location of ischemia by MPS (kappa = 1.0), whereas the location of ST depression did not (kappa = 0.20).Conclusions: Stress-induced ST elevation, with or without concomitant ST depression, is predictive of the presence, amount and location of myocardial ischemia assessed by MPS, whereas stress induced ST depression without concomitant ST elevation is not. (C) 2016 Elsevier Inc. All rights reserved.

SummaryBackgroundAdenosine is widely used as a vasodilator agent in myocardial perfusion imaging. Caffeine inhibits the effect, but the time of caffeine abstinence needed is under discussion and varies from 12 to 24 h. Therefore, our aim was to examine whether the time of caffeine abstinence affects the hyperaemic response using quantification of coronary sinus flow (CSF) with cardiac magnetic resonance (CMR) during adenosine infusion.MethodsHealthy individuals (n = 16, eight females, age 41 ± 3 years) underwent two CMR examinations with 12 and 24 h of caffeine abstinence. CSF was quantified with phase‐contrast velocity mapping (PC‐)CMR during adenosine infusion (140 μg kg−1 min−1) and rest and the CSF reserve between adenosine and rest was calculated. Myocardial perfusion (MP) was calculated as CSF × heart rate/left ventricular mass. Cardiac output (CO) was quantified using PC‐CMR of the ascending aorta.ResultsThe CSF reserve was lower after 12 h abstinence compared to 24 h (4·31 ± 0·57 versus 5·32 ± 0·76, P = 0·03). In six of 16 subjects (38%), CSF reserve was >30% higher with longer caffeine abstinence. MP during adenosine was lower after 12 h compared to 24 h caffeine abstinence (3·59 ± 0·37 versus 4·23 ± 0·28 ml min−1g−1; P = 0·046). The increase in CO during adenosine between the two occasions did not differ (55 ± 7% and 55 ± 6%, P = 0·11). Interobserver variability for CSF/heartbeat was −0·05 ± 1·00 ml.ConclusionsHyperaemia during adenosine is lower in some patients with 12 h of caffeine abstinence compared to 24 h. Longer caffeine abstinence, that is 24 h, is of value before pharmacological stress testing as the individual response is not known and the individual variation is large.

Background: Many graphical methods for displaying ST-segment deviation in the ECG have been tried for enhancing decision-making in patients with suspected acute coronary syndromes. Computed electrocardiographic imaging (CEI), based on a mathematical inverse solution, has been recently applied to transform ST-J point measurements made in conventional 12-lead ECG into a display of epicardial potentials in bull's-eye format. The purpose of this study is to assess utility of CEI in the clinical setting.Methods: In 99 patients with stable coronary disease, 12-lead ECGs were recorded during elective percutaneous coronary intervention (PCI), first before balloon-catheter insertion and then when an intracoronary balloon blocked blood supply to a region of myocardium for more than 4 minutes (typically 5 minutes). Four groups of patients were additionally studied, namely those with preexcitation, pericarditis, early repolarization syndrome (ERS), and left ventricular hypertrophy (LVH) with strain. Comparisons between performances of published criteria for ST-elevation myocardial infarction (STEMI) and quantitative as well as visual assessment of CEI images were based on sensitivities and specificities.Results: Visual assessment of CEI outperformed STEMI criteria. This was especially evident for the capability of detecting LCx occlusion with sensitivities for STEMI criteria = 35% and for visual assessment of CEI by 2 physicians = 71%, i. e. twice as many patients were correctly identified by CEI. False positive rates for CEI were low in patients with LVH with strain as well as with preexcitation for both methods. For pericarditis and ERS, visual as well as quantitative assessment of CEI performed better than STEMI criteria.Conclusion: Visual assessment of CEI is a promising method for increasing the accuracy of ECG-based triage to PCI or conservative care. (C) 2013 Elsevier Inc. All rights reserved.

SummaryBackgroundStudies of cardiovascular deconditioning are primarily carried out after experimental bed rest. No previous study has followed the cardiovascular effects of decreased and resumed physical activity in athletes after acute physical injury and convalescence. Anterior cruciate ligament (ACL) injury causes a significantly decreased activity level over a long period, making it an ideal model for studying effects of deconditioning and reconditioning. Therefore, the aim of this study was to investigate how cardiac dimensions and maximal exercise capacity change after an ACL‐injury.MethodSeventeen athletes (5 women) were included. Cardiac magnetic resonance (CMR) was performed within 5 days of the injury (CMR1), before endurance training was resumed (CMR2) and 6 months after the second scan (CMR3). Maximal exercise testing was performed on the same day as CMR2 and 3.ResultsThe deconditioning phase between CMR1 and CMR2 was 59 ± 28 days. Total heart volume (THV) decreased with −3·1 ± 6·7%, P = 0·056. Between CMR2 and 3 (reconditioning), THV increased significantly (2·5 ± 4·6%, P<0·05). Left and right ventricular EDV decreased during deconditioning (−3·0 ± 5·6% and −4·7 ± 6·6%) and increased during reconditioning (1·7 ± 3·9% and 2·6 ± 6·2%) however not statistically significant. Left ventricular mass (LVM) remained unchanged. VO2 peak (mlmin−1kg−1) increased significantly during the reconditioning phase (6·1 ± 5·3%, P<0·001).ConclusionPhysiological cardiac adaptation to deconditioning and reconditioning caused by severe knee injury with maintained normal daily living during convalescence was smaller than previously shown in bed rest studies. Total heart volume and VO2 peak were significantly affected by reconditioning whilst LVEDV, RVEDV and LVM remained unchanged over the study period.

Background: The time from symptom onset to reperfusion in acute myocardial infarction (MI) has been shown to be a poor predictor of patient outcome. Acute electrocardiographic (ECG) changes, however, have been shown useful for estimated acuteness of myocardial ischemia using the Anderson-Wilkins ECG ischemia acuteness score (AW-acuteness score). The aim was to study whether acute ischemic ECG changes can predict the amount of salvageable myocardium in patients with acute ST-elevation MI.Methods: Thirty-eight patients treated with primary percutaneous coronary intervention for first-time ST-elevation MI were retrospectively enrolled. Myocardium at risk (MaR) was determined by myocardial perfusion single photon emission computed tomography acutely or by T2-weighted cardiac magnetic resonance after 1 week, at the same time when final MI size was determined by late gadolinium enhancement. Myocardial salvage was calculated as (MaR - MI size)/MaR and compared with AW-acuteness score and time from symptom onset to primary percutaneous coronary intervention.Results: The AW-acuteness score correlated significantly with salvageable myocardium for right coronary artery (RCA) occlusions (r = -0.57; P = .02) but not for left anterior descending artery (LAD) occlusions (r = 0.04; P = .88). Time from symptom onset did not correlate with the amount of salvageable myocardium (LAD, r = 0.04 and P = .87; RCA, r = 0.40 and P = .13).Conclusions: There is a moderate correlation between AW-acuteness score and salvageable myocardium in patients with acute RCA occlusion but not in patients with LAD occlusion. (C) 2011 Elsevier Inc. All rights reserved.

BACKGROUND:An early sign of heart failure (HF) is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO2peak) which has previously been shown to be closely related to total heart volume (THV). Thus, the aim of this study was to derive a VO2peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes) were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO2peak/THV ratio was then derived and tested.RESULTS:Peak oxygen uptake was strongly correlated to THV (r2 = 0.74, p < 0.001) in the control subjects, but not for the patients (r2 = 0.0002, p = 0.95). The VO2peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p < 0.001). In a multivariate analysis the VO2peak/THV ratio was the only independent predictor of presence of HF (p < 0.001).CONCLUSIONS:The VO2peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels.

Background It is of great clinical importance to exclude myocardial infarction in patients with suspected coronary artery disease who do not have stress-induced ischemia. The diagnostic use of myocardial perfusion single-photon emission computed tomography (SPECT) in this situation is sometimes complicated by attenuation artifacts that mimic myocardial infarction. Imaging in the prone position has been suggested as a method to overcome this problem. Methods In this study, 52 patients without known prior infarction and no stress-induced ischemia on SPECT imaging were examined in both supine and prone position. The results were compared with cardiac magnetic resonance imaging (CMR) with delayed-enhancement technique to confirm or exclude myocardial infarction. Results There were 63 defects in supine-position images, 37 of which disappeared in the prone position. None of the 37 defects were associated with myocardial infarction by CMR, indicating that all of them represented attenuation artifacts. Of the remaining 26 defects that did not disappear on prone imaging, myocardial infarction was confirmed by CMR in 2; the remaining 24 had no sign of ischemic infarction but 2 had other kinds of myocardial injuries. In 3 patients, SPECT failed to detect small scars identified by CMR. Conclusion Perfusion defects in the supine position that disappeared in the prone position were caused by attenuation, not myocardial infarction. Hence, imaging in the prone position can help to rule out ischemic heart disease for some patients admitted for SPECT with suspected but not documented ischemic heart disease. This would indicate a better prognosis and prevent unnecessary further investigations and treatment.

Introduction Based on animal studies, it is currently accepted that duration of ischemia is a major determinant of the ability to salvage jeopardized myocardium by restoring the coronary blood flow and myocardial perfusion. In experimental animal studies it is possible to determine the exact time of occlusion as well as to ensure complete, persistent ischemia during the time of coronary occlusion. In humans, however, it is impossible to determine either the exact time of acute occlusion or whether spontaneous reperfusion and re-occlusion has occurred prior to the time of reperfusion therapy.

Background: The potential for salvage of jeopardized myocardium during coronary occlusion decreases as the duration of persistent ischemia is prolonged. Thus, it is important to be able to assess the acuteness of ischemia as a patient presents with signs of acute coronary syndrome. The aim of this study was to compare ECG estimate of ischemic acuteness and time from pain onset for predicting myocardial salvage in patients with first-time myocardial infarction (MI). Methods: Thirteen patients with acutely revascularized first-time MI were studied. All patients had 99mTc tetrofosmin injected and an ECG recorded prior to the PCI. TIMI III flow was obtained in all patients. Single photon emission computed tomography (SPECT) was undertaken within 3 hours of the PCI to assess the myocardium at risk (MaR). Delayed contrast-enhanced magnetic resonance imaging (DE-MRI) was performed 1 week after admission for assessment of infarct size (IS) and infarct transmurality (IT). A salvage index was calculated as (MaR-IS)/MaR. The acuteness of ischemia was estimated both from patient history and from the Anderson-Wilkins (AW) acuteness score of the pre-PCI ECG. Results: The figure shows the relationship between time of symptom onset and salvage index (A) and IT (C) as well as the relationship between AW acuteness score and salvage index (B) and IT (D). The time of symptom onset did not correlate with salvage index or IT. The AW acuteness score, however, showed a significant relationship with both salvage index and IT. Conclusions: The initial ECG changes are superior to time from symptom onset to PCI for predicting myocardial salvage and IT in patients undergoing PCI of first-time MI.

BACKGROUND:Previous studies have shown reduced high-frequency QRS components (HF-QRS) after acute myocardial infarction (MI). The purpose of this study was to investigate serial changes in HF-QRS during the first year following acute MI.METHODS:A total of 75 patients were included. Standard- and high-frequency ECGs were recorded on five occasions during the year following the MI (a few days after the MI, after 6 weeks, and after 3, 6 and 12 months).RESULTS:There was a statistically significant increase in HF-QRS during the follow-up year (P = 0.002). There were no significant differences in HF-QRS when comparing either the infarct location or the presence or absence of reperfusive therapy. Large differences in HF-QRS were observed, both intra-individually and inter-individually, during the year.CONCLUSIONS:There was a statistically significant increase in HF-QRS during the year following acute MI.