Diagnostic confidence with quantitative cardiovascular magnetic resonance perfusion mapping increases with increased coverage of the left ventricle.

BACKGROUND: Quantitative cardiovascular magnetic resonance (CMR) first pass perfusion maps are conventionally acquired with 3 short-axis (SAX) views (basal, mid, and apical) in every heartbeat (3SAX/1RR). Thus, a significant part of the left ventricle (LV) myocardium, including the apex, is not covered. The aims of this study were 1) to investigate if perfusion maps acquired with 3 short-axis views sampled every other RR-interval (2RR) yield comparable quantitative measures of myocardial perfusion (MP) as 1RR and 2) to assess if acquiring 3 additional perfusion views (i.e., total of 6) every other RR-interval (2RR) increases diagnostic confidence. METHODS: In 287 patients with suspected ischemic heart disease stress and rest MP were performed on clinical indication on a 1.5T MR scanner. Eighty-three patients were examined by acquiring 3 short-axis perfusion maps with 1RR sampling (3SAX/1RR); for which also 2RR maps were reconstructed. Additionally, in 103 patients 3 short-axis and 3 long-axis (LAX; 2-, 3, and 4-chamber view) perfusion maps were acquired using 2RR sampling (3SAX + 3LAX/2RR) and in 101 patients 6 short-axis perfusion maps using 2RR sampling (6SAX/2RR) were acquired. The diagnostic confidence for ruling in or out stress-induced ischemia was scored according to a Likert scale (certain ischemia [2 points], probably ischemia [1 point], uncertain [0 points], probably no ischemia [1 point], certain no ischemia [2 points]). RESULTS: There was a strong correlation (R = 0.99) between 3SAX/1RR and 3SAX/2RR for global MP (mL/min/g). The diagnostic confidence score increased significantly when the number of perfusion views was increased from 3 to 6 (1.24 ± 0.68 vs 1.54 ± 0.64, p < 0.001 with similar increase for 3SAX+3LAX/2RR (1.29 ± 0.68 vs 1.55 ± 0.65, p < 0.001) and for 6SAX/2RR (1.19 ± 0.69 vs 1.53 ± 0.63, p < 0.001). CONCLUSION: Quantitative perfusion mapping with 2RR sampling of data yields comparable perfusion values as 1RR sampling, allowing for the acquisition of additional views within the same perfusion scan. The diagnostic confidence for stress-induced ischemia increases when adding 3 additional views, short- or long axes, to the conventional 3 short-axis views. Thus, future development and clinical implementation of quantitative CMR perfusion should aim at increasing the LV coverage from the current standard using 3 short-axis views.

Contractility, ventriculoarterial coupling, and stroke work after acute myocardial infarction using CMR-derived pressure-volume loop data.

BACKGROUND: Noninvasive left ventricular (LV) pressure-volume (PV) loops derived by cardiac magnetic resonance (CMR) have recently been shown to enable characterization of cardiac hemodynamics. Thus, such PV loops could potentially provide additional diagnostic information such as contractility, arterial elastance (Ea ) and stroke work (SW) currently not available in clinical routine. This study sought to investigate to what extent PV-loop variables derived with a novel noninvasive method can provide incremental physiological information over cardiac dimensions and blood pressure in patients with acute myocardial infarction (MI). METHODS: A total of 100 patients with acute MI and 75 controls were included in the study. All patients underwent CMR 2-6 days after MI including assessment of myocardium at risk (MaR) and infarct size (IS). Noninvasive PV loops were generated from CMR derived LV volumes and brachial blood pressure measurements. The following variables were quantified: Maximal elastance (Emax ) reflecting contractility, Ea , ventriculoarterial coupling (Ea /Emax ), SW, potential energy, external power, energy per ejected volume, and efficiency. RESULTS: All PV-loop variables were significantly different in MI patients compared to healthy volunteers, including contractility (Emax : 1.34 ± 0.48 versus 1.50 ± 0.41 mmHg/mL, p = .024), ventriculoarterial coupling (Ea /Emax : 1.27 ± 0.61 versus 0.73 ± 0.17, p < .001) and SW (0.96 ± 0.32 versus 1.38 ± 0.32 J, p < .001). These variables correlated to both MaR and IS (Emax : r2 = 0.25 and r2 = 0.29; Ea /Emax : r2 = 0.36 and r2 = 0.41; SW: r2 = 0.21 and r2 = 0.25). CONCLUSIONS: Noninvasive PV-loops provide physiological information beyond conventional diagnostic variables, such as ejection fraction, early after MI, including measures of contractility, ventriculoarterial coupling, and SW.

Influence of different time framings, reconstruction algorithms and post-processing methods on the quantification of myocardial blood flow from 13 N-NH3 PET images.

BACKGROUND: The aim was to investigate to what extent the quantification of myocardial blood flow (MBF) from dynamic 13 N-NH3 positron emission tomography (PET) images is affected by time frame schemes, time-of-flight (ToF), reconstruction algorithms, blood pool volume of interest (VOI) locations and compartment models in patients with suspected chronic coronary syndrome. METHODS: A standard MBF value was determined from 25 patients' rest/stress 13 N-NH3 PET/CT images reconstructed with ordered subset expectation maximization (OSEM), 5 s time frame for the first frames without ToF, subsequently analyzed using a basal VOI and the deGrado compartment model. MBFs calculated using 2 or 10 s for the first frames, ToF, block-sequential regularized expectation maximization (BSREM), apical or large VOI, Hutchins or Krivokapich compartment models were compared to MBFstandard in Bland-Altman plots (bias ± SD). RESULTS: Good agreement in global rest/stress MBF (mL/min/g) was found when changing the time frame scheme or reconstruction algorithm (MBFstandard vs. MBF2s : -0.02 ± 0.06; MBF10s : 0.01 ± 0.07; MBFBSREM : 0.01 ± 0.07), while a lower level of agreement was found when altering the other factors (MBFstandard vs. MBFToF : -0.07 ± 0.10; MBFapical VOI : -0.27 ± 0.25; MBFlarge VOI : -0.11 ± 0.10; MBFHutchins : -0.08 ± 0.10; MBFKrivokapich : -0.47 ± 0.50). CONCLUSIONS: Quantification of MBF from 13 N-NH3 PET images is more affected by choice of compartment models, ToF and blood pool VOIs than by different time frame schemes and reconstruction algorithms.

Prognostic utility and characterization of left ventricular hypertrophy using global thickness.

Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12-1.20], p < 0.001), followed by GTI (HR 1.14[1.09-1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35-1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).

Coronary microvascular dysfunction in Takotsubo syndrome and associations with left ventricular function.

AIMS: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. METHODS AND RESULTS: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (-11 vs. -14, P < 0.001 and -12 vs. -15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R2  = 0.15, P = 0.002 and R2  = 0.18, P = 0.007, respectively) and CMR-derived (R2  = 0.09, P = 0.025 and R2  = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.

Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events.

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.

Stress native T1 and native T2 mapping compared to myocardial perfusion reserve in long-term follow-up of severe Covid-19.

Severe Covid-19 may cause a cascade of cardiovascular complications beyond viral pneumonia. The severe inflammation may affect the microcirculation which can be assessed by cardiovascular magnetic resonance (CMR) imaging using quantitative perfusion mapping and calculation of myocardial perfusion reserve (MPR). Furthermore, native T1 and T2 mapping have previously been shown to identify changes in myocardial perfusion by the change in native T1 and T2 during adenosine stress. However, the relationship between native T1, native T2, ΔT1 and ΔT2 with myocardial perfusion and MPR during long-term follow-up in severe Covid-19 is currently unknown. Therefore, patients with severe Covid-19 (n = 37, median age 57 years, 24% females) underwent 1.5 T CMR median 292 days following discharge. Quantitative myocardial perfusion (ml/min/g), and native T1 and T2 maps were acquired during adenosine stress, and rest, respectively. Both native T1 (R2 = 0.35, p < 0.001) and native T2 (R2 = 0.28, p < 0.001) correlated with myocardial perfusion. However, there was no correlation with ΔT1 or ΔT2 with MPR, respectively (p > 0.05 for both). Native T1 and native T2 correlate with myocardial perfusion during adenosine stress, reflecting the coronary circulation in patients during long-term follow-up of severe Covid-19. Neither ΔT1 nor ΔT2 can be used to assess MPR in patients with severe Covid-19.

Diagnostic accuracy for CZT gamma camera compared to conventional gamma camera technique with myocardial perfusion single-photon emission computed tomography: Assessment of myocardial infarction and function.

BACKGROUND: The solid-state cadmium-zinc-telluride (CZT) gamma camera for myocardial perfusion single-photon emission computed tomography (MPS) has theoretical advantages compared to the conventional gamma camera technique. This includes more sensitive detectors and better energy resolution. We aimed to explore the diagnostic performance of gated MPS with a CZT gamma camera compared to a conventional gamma camera for detection of myocardial infarct (MI) and assessment of left ventricular (LV) volumes and ejection fraction (LVEF), using cardiac magnetic resonance (CMR) as the reference method. METHODS: Seventy-three patients (26% female) with known or suspected chronic coronary syndrome were examined with gated MPS using both a CZT gamma camera and a conventional gamma camera as well as with CMR. Presence and extent of MI on MPS and late gadolinium enhancement (LGE) CMR was evaluated. For LV volumes, LVEF and LV mass, gated MPS images and cine CMR images were evaluated. RESULTS: MI was found in 42 patients on CMR. The overall sensitivity, specificity, positive and negative predictive values for the CZT and the conventional gamma camera were the same (67%, 100%, 100% and 69%). For infarct size > 3% on CMR, the sensitivity was 82% for the CZT and 73% for the conventional gamma camera, respectively. LV volumes were significantly underestimated by MPS compared to CMR (P ≤ .002 for all measures). The underestimation was slightly less pronounced for the CZT compared to the conventional gamma camera (2-10 mL, P ≤ .03 for all measures). For LVEF, however, accuracy was high for both gamma cameras. CONCLUSION: Differences between a CZT and a conventional gamma camera for detection of MI and assessment of LV volumes and LVEF are small and do not appear to be clinically significant.

Infarct quantification with cardiovascular magnetic resonance using "standard deviation from remote" is unreliable: validation in multi-centre multi-vendor data.

BACKGROUND: The objective of the study was to investigate variability and agreement of the commonly used image processing method "n-SD from remote" and in particular for quantifying myocardial infarction by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). LGE-CMR in tandem with the analysis method "n-SD from remote" represents the current reference standard for infarct quantification. This analytic method utilizes regions of interest (ROIs) and defines infarct as the tissue with a set number of standard deviations (SD) above the signal intensity of remote nulled myocardium. There is no consensus on what the set number of SD is supposed to be. Little is known about how size and location of ROIs and underlying signal properties in the LGE images affect results. Furthermore, the method is frequently used elsewhere in medical imaging often without careful validation. Therefore, the usage of the "n-SD" method warrants a thorough validation. METHODS: Data from 214 patients from two multi-center cardioprotection trials were included. Infarct size from different remote ROI positions, ROI size, and number of standard deviations ("n-SD") were compared with reference core lab delineations. RESULTS: Variability in infarct size caused by varying ROI position, ROI size, and "n-SD" was 47%, 48%, and 40%, respectively. The agreement between the "n-SD from remote" method and the reference infarct size by core lab delineations was low. Optimal "n-SD" threshold computed on a slice-by-slice basis showed high variability, n = 5.3 ± 2.2. CONCLUSION: The "n-SD from remote" method is unreliable for infarct quantification due to high variability which depends on different placement and size of remote ROI, number "n-SD", and image signal properties related to the CMR-scanner and sequence used. Therefore, the "n-SD from remote" method should not be used, instead methods validated against an independent standard are recommended.

Quantitative myocardial perfusion during stress using CMR is impaired in healthy Middle Eastern immigrants without CV risk factors.

Middle Eastern immigrants constitute a growing proportion of the European population and compared to native Swedes are more insulin resistant, which can contribute to atherosclerosis. Quantitative first pass perfusion (qFPP) using cardiovascular magnetic resonance (CMR) can detect early signs of cardiovascular disease (CVD). The aim was to study if myocardial perfusion differs between healthy male Middle Eastern immigrants and native male Swedes. Eighteen Iraqi- and twelve Swedish born controls, all males, never smokers with no CVD risk factors were included. Global myocardial perfusion at rest and stress was assessed using qFPP and by phase-contrast CMR imaging of coronary sinus flow. Quantitative first pass perfusion analysis (mean ± SD) demonstrated no difference at rest between Iraqi and Swedish males (0.8 ± 0.2 vs 1.0 ± 0.4 ml/min/g, P = 0.38) but lower perfusion during adenosine in Iraqi males (2.9 ± 0.7 vs 3.5 ± 0.7 ml/min/g, P = 0.02). Myocardial perfusion assessed by coronary sinus flow demonstrated similar results with no difference in resting perfusion between groups (0.7 ± 0.2 vs 0.8 ± 0.2 ml/min/g, P = 0.21) but a lower perfusion during adenosine in the Iraqi group (3.0 ± 0.2 vs 3.7 ± 0.6 ml/min/g, P = 0.01. Myocardial perfusion during adenosine stress was lower in healthy Iraqi immigrants compared to Swedish controls suggesting impaired microvascular function and risk of underestimating CVD risk in healthy individuals of Middle Eastern origin.

Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina.

BACKGROUND: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. METHODS: Twenty-three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress-induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first-pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. RESULTS: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). CONCLUSIONS: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex-specific normal limits when assessing quantitative MP.

Anterior STEMI associated with decreased strain in remote cardiac myocardium.

To assess (1) global longitudinal strain (GLS) by feature tracking cardiac magnetic resonance (CMR) in the sub-acute and chronic phases after ST-elevation infarction (STEMI) and compare to GLS in healthy controls, and (2) the evolution of GLS and regional longitudinal strain (RLS) over time, and their relationship to infarct location and size. Seventy-seven patients from the CHILL-MI-trial (NCT01379261) who underwent CMR 2-6 days and 6 months after STEMI and 27 healthy controls were included for comparison. Steady state free precession (SSFP) long-axis cine images were obtained for GLS and RLS, and late gadolinium enhancement (LGE) images were obtained for infarct size quantifications. GLS was impaired in the sub-acute (- 11.8 ± 3.0%) and chronic phases (- 14.3 ± 2.9%) compared to normal GLS in controls (- 18.4 ± 2.4%; p < 0.001 for both). GLS improved from sub-acute to chronic phase (p < 0.001). GLS was to some extent determined by infarct size (sub-acute: r2 = 0.2; chronic: r2 = 0.2, p < 0.001). RLS was impaired in all 6 wall-regions in LAD infarctions in both the sub-acute and chronic phase, while LCx and RCA infarctions had preserved RLS in remote myocardium at both time points. Global longitudinal strain is impaired sub-acutely after STEMI and improvement is seen in the chronic phase, although not reaching normal levels. Global longitudinal strain is only moderately determined by infarct size. Regional longitudinal strain is most impaired in the infarcted region, and LAD infarctions have effects on the whole heart. This could explain why LAD infarcts are more serious than the other culprit vessel infarctions and more often cause heart failure.

Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial.

INTRODUCTION: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS. METHODS AND ANALYSIS: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022. ETHICS AND DISSEMINATION: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible. TRIAL REGISTRATION NUMBER: NCT04121949; Pre-results.

Low diagnostic yield of ST elevation myocardial infarction amplitude criteria in chest pain patients at the emergency department.

OBJECTIVES: To evaluate the diagnostic yield of the ECG criteria for ST-elevation myocardial infarction in a large cohort of emergency department chest pain patients, and to determine whether extended ECG criteria or reciprocal ST depression can improve accuracy. Design: Observational, register-based diagnostic study on the accuracy of ECG criteria for ST-elevation myocardial infarction. Between Jan 2010 and Dec 2014 all patients aged ≥30 years with chest pain who had an ECG recorded within 4 h at two emergency departments in Sweden were included. Exclusion criteria were: ECG with poor technical quality; QRS duration ≥120 ms; ECG signs of left ventricular hypertrophy; or previous coronary artery bypass surgery. Conventional and extended ECG criteria were applied to all patients. The main outcome was acute myocardial infarction (AMI) and an occluded/near-occluded coronary artery at angiography. Results: Finally, 19932 patients were included. Conventional ECG criteria for ST elevation myocardial infarction were fulfilled in 502 patients, and extended criteria in 1249 patients. Sensitivity for conventional ECG criteria in diagnosing AMI with coronary occlusion/near-occlusion was 17%, specificity 98% and positive predictive value 12%. Corresponding data for extended ECG criteria were 30%, 94% and 8%. When reciprocal ST depression was added to the criteria, the positive predictive value rose to 24% for the conventional and 23% for the extended criteria. Conclusions: In unselected chest pain patients at the emergency department, the diagnostic yield of both conventional and extended ECG criteria for ST-elevation myocardial infarction is low. The PPV can be increased by also considering reciprocal ST depression.

Appropriate coronary revascularization can be accomplished if myocardial perfusion is quantified by positron emission tomography prior to treatment decision.

BACKGROUND: Many patients undergo percutaneous coronary intervention (PCI) without the use of non-invasive stress testing prior to treatment. The aim of this study was to determine the potential added value of guiding revascularization by quantitative assessment of myocardial perfusion prior to intervention. METHODS AND RESULTS: Thirty-three patients (10 females) with suspected or established CAD who had been referred for a clinical coronary angiography (CA) with possibility for PCI were included. Adenosine stress and rest 13N-NH3 PET, cardiac magnetic resonance (CMR), and cardiopulmonary exercise test were performed 4 ± 3 weeks before and 5 ± 1 months after CA. The angiographer was blinded to the PET and CMR results. Myocardial flow reserve (MFR) < 2.0 by PET was considered abnormal. A PCI was performed in 19/33 patients. In 41% (11/27) of the revascularized vessel territories, a normal regional MFR was found prior to the PCI and no improvement in MFR was found at follow-up (P = 0.9). However, vessel territories with regional MFR < 2.0 at baseline improved significantly after PCI (P = 0.003). Of the 14 patients not undergoing PCI, four had MFR < 2.0 in one or more coronary territories. CONCLUSION: Assessment of quantitative myocardial perfusion prior to revascularization could lead to more appropriate use of CA when managing patients with stable CAD.

To what extent are perfusion defects seen by myocardial perfusion SPECT in patients with left bundle branch block related to myocardial infarction, ECG characteristics, and myocardial wall motion?

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evolution of left ventricular function among subjects with ST-elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: Atrioventricular plane displacement (AVPD) reflects longitudinal left ventricular (LV) systolic function, and wall thickening (WT) regional radial LV function. The temporal evolution of these measures after STEMI with CMR has not been evaluated. We aimed to investigate how AVPD and WT are affected globally and regionally from the sub-acute to the chronic phase after ST-elevation myocardial infarction (STEMI). METHODS: Healthy volunteers without cardiovascular disease and medication (controls, n = 20) and patients from the CHILL-MI study ( NCT01379261 ) prospectively underwent magnetic resonance imaging (MRI) 2-6 days and 6 months after STEMI (n = 77). CHILL-MI randomized STEMI-patients to cooling therapy initiated before reperfusion or standard of care. AVPD was measured at six points in three long axis cine images and wall thickening in short axis cine images. Infarction was quantified using late gadolinium enhancement (LGE) and used to define infarct and remote segments. RESULTS: There were no difference in AVPD either at acute or chronic phase (p = 0.90 and p = 0.40) or WT (p = 0.85 and p = 0.99) between patients randomized to cooling therapy and standard of care. Therefore, the results are presented for the pooled cohort. Global AVPD was decreased in both the sub-acute (12 ± 2 mm, p < 0.001) and the chronic phase (13 ± 2 mm, p < 0.001) compared to controls (15 ± 2 mm) with a partial recovery of AVPD (p < 0.001) in the chronic phase. Patients with left anterior descending (LAD) and right coronary artery (RCA) infarcts had decreased AVPD in the chronic phase in both infarcted and remote segments. Mean WT was decreased in patients with LAD infarction both in the sub-acute and the chronic phase in both infarcted and remote segments. The decrease in WT in patients with RCA and left circumflex (LCx) infarcts was more affected in the infarcted segments, especially in the chronic phase. CONCLUSION: AVPD was a global rather than regional marker of cardiac function in this STEMI study and this may explain the prognostic importance of local measurements of mitral annular plane systolic excursion (MAPSE). The decrease in WT in remote myocardium even in the chronic phase needs to be taken into consideration when combining functional measurements with infarct quantification for diagnosis of post-ischemic stunning and hibernation.

Worst lead ST deviation and resolution of ST elevation at one hour for prediction of myocardial salvage, infarct size, and microvascular obstruction in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: ECG changes after revascularization predicts improved outcome for patients with ST-elevation myocardial infarction (STEMI). Worst lead residual (WLR) ST deviation and resolution of worst lead ST elevation (rST elevation) are simple measures that can be obtained early after PCI. The objective of the current study was to investigate whether simple ECG measures, obtained one hour following PCI, could predict cardiac magnetic resonance (CMR)-derived myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) in patients with STEMI included in the MITOCARE trial. METHODS: The MITOCARE trial included 165 patients with a first-time STEMI presenting within six hours of symptom onset. The current analysis included patients that had an ECG recorded at baseline and one hour after PCI and underwent CMR imaging after 3-5 days. Independent core laboratories determined WLR ST deviation, rST elevation, and the CMR variables (MSI, IS, and MVO). RESULTS: 83 patients with a mean age of 61 years were included. 83.1% were males and 41% had anterior infarctions. In logistic regression models, WLR ST deviation was a statistically significant predictor of IS (OR 2.2, 95% CI 1.3-3.8) and MVO (OR 2.8, 95% CI 1.5-5.2), but not of MSI (OR 0.8, 95% CI 0.5-1.2). rST elevation showed a trend toward a significant association with IS (OR 0.3, 95% CI 0.1-1.0), but not with the other CMR variables. CONCLUSION: WLR ST deviation one hour after PCI was a predictor of IS and MVO. WLR ST deviation, a measure easily obtained from ECGs following PCI, may provide important prognostic information in patients with STEMI.