Layer-specific fast strain-encoded cardiac magnetic resonance imaging aids in the identification and discrimination of acute myocardial injury: a prospective proof-of-concept study.

BACKGROUND: Acute myocardial injury is a common diagnosis in the emergency department and differential diagnoses are numerous. Cardiac magnetic resonance (CMR) strain sequences, such as fast strain ENCoded (fSENC), are early predictors of myocardial function loss. This study assessed the potential diagnostic and prognostic benefits of a layer-specific approach. METHODS: For this prospective study, patients in the emergency department fulfilling rule-in criteria for non-ST-elevation myocardial infarction (NSTEMI) received an ultra-fast fSENC CMR. Volunteers without cardiac diseases (controls) were recruited for comparison. Measurements were performed in a single heartbeat acquisition to measure global longitudinal strain (GLS) and segmental longitudinal strain and dysfunctional segments. The GLS was measured in two layers and a difference (GLSdifference = GLSepicardial - GLSendocardial) was calculated. The performance of those strain features was compared to standard care (physical examination, cardiac biomarkers, electrocardiogram). According to the final diagnosis after discharge, patients were divided into groups and followed up for 2 years. RESULTS: A total of 114 participants, including 50 controls, were included. The 64 patients (51 male) were divided into a NSTEMI (25), myocarditis (16), and other myocardial injury group (23). GLS served as a potent predictor of myocardial injury (area under the curve (AUC) 91.8%). The GLSdifference provided an excellent diagnostic performance to identify a NSTEMI (AUC 83.2%), further improved by including dysfunctional segments (AUC 87.5%, p = 0.01). An optimal test was achieved by adding fSENC to standard care (AUC 95.5%, sensitivity 96.0%, specificity 86.5%, p = 0.03). No death occurred in 2 years for patients with normal GLS and ≤5 dysfunctional segments, while three patients died that showed abnormal GLS or >5 dysfunctional segments. CONCLUSIONS: Layer-specific strain is a potential new marker with high diagnostic performance in the identification and differentiation of acute myocardial injuries.

Safety of dobutamine or adenosine stress cardiac magnetic resonance imaging in patients with left ventricular thrombus.

BACKGROUND: Left ventricular (LV) thrombus formation is a common but potentially serious complication, typically occurring after myocardial infarction. Due to perceived high thromboembolic risk and lack of safety data, stress cardiac magnetic resonance (CMR) imaging especially with dobutamine is usually avoided despite its high diagnostic yield. This study aimed to investigate the characteristics, safety and outcome of patients with LV thrombus undergoing dobutamine or vasodilator stress CMR. METHODS: Patients undergoing stress CMR with concomitant LV thrombus were retrospectively included. Risk factors, comorbidities, and previous embolic events were recorded. Periprocedural safety was assessed for up to 48 h following the examination. Major adverse cardiac events (MACE) 12 months before the diagnosis were compared to 12 months after the exam and between patients and a matched control group. Additionally, patients were followed up for all-cause mortality. RESULTS: 95 patients (78 male, 65 ± 10.7 years) were included. Among them, 43 patients underwent dobutamine (36 high-dose, 7 low-dose) and 52 vasodilator stress CMR. Periprocedural safety was excellent with no adverse events. During a period of 24 months, 27 MACE (14.7%) occurred in patients and controls with no statistical difference between groups. During a median follow-up of 33.7 months (IQR 37.6 months), 6 deaths (6.3%) occurred. Type of stress agent, thrombus mobility, or protrusion were not correlated to embolic events or death. CONCLUSION: The addition of a stress test to a CMR exam is safe and does increase the generally high cardioembolic event rate in LV thrombus patients. Therefore, it is useful to support reperfusion decision-making.

Safety, accuracy, and prediction of prognosis in patients with end-stage chronic kidney disease undergoing dobutamine stress cardiac magnetic resonance imaging.

Introduction: Advanced chronic kidney disease (CKD) is an independent risk factor for coronary artery disease (CAD). Due to its unique uremia-derived pathophysiology of atherosclerosis and the limitations of using potentially harmful contrast agents, the best non-invasive approach to assess CAD in these patients remains unclear. We sought to investigate the accuracy, safety, and prognosis of patients with severe CKD undergoing dobutamine stress cardiac magnetic resonance imaging (CMR). Materials and methods: In this retrospective, single-center study, patients on dialysis or with a glomerular filtration rate of <15 ml/min/1.73 m2 who underwent dobutamine stress CMR were included. A rest and stress wall motion analysis was performed using dobutamine/atropine as stressor. The target heart rate was 85% of the maximum heart rate. Periprocedural adverse events and 1-year follow-up data were obtained. Results: A total of 176 patients (127 men, 49 women) with a mean age of 60.9 ± 14.7 years were included, of which 156 patients were on permanent dialysis. Short-term symptoms such as angina or shortness of breath during stress CMR were frequent (22.1%), but major complications were rare (one patient with myocardial infarction, 0.6%). The 1-year event rate was high (16.4%) with a significant independent correlation to reduced ejection fraction at rest (p = 0.037) and failure to achieve the target heart rate (p = 0.029). The overall accuracy for predicting significant CAD was good (sensitivity of 71.4%, specificity of 98.4%) and excellent if the target heart rate was achieved (83.3%, 97.9%). A negative stress CMR was highly predictive for the absence of major adverse cardiac event or any coronary revascularization during the 1-year follow-up (negative predictive value of 95.0%). Discussion: Dobutamine stress CMR is a safe and accurate diagnostic imaging technique in patients at advanced stages of chronic kidney disease. A reduced ejection fraction and the inability to reach the target heart rate are independent predictors of a poor outcome.

Hypverventilation strain CMR imaging in patients with acute chest pain.

In patients with suspected acute coronary syndrome high-sensitivity cardiac tropnonin T is used for rapid patient triage. Some acute coronary syndrome patients assigned to the observe zone based on high-sensitivity cardiac troponin T after 1 h require further diagnostic testing. Fast-strain encoded CMR imaging with breathing maneuvers may accelerate diagnostic work-up and identify patients suffering from acute coronary syndrome. Patients presenting with acute chest pain (high-sensitivity cardiac troponin T level 5-52 ng/L) were prospectively enrolled (consecutive sampling, time of recruitment: 09/18-06/19). Fast-strain-encoded imaging was performed within the 1-h timeframe (0 h/1 h algorithm) prior to 2nd high-sensitivity troponin T lab results. Images were acquired at rest as well as after 1-min of hyperventilation followed by a short breath-hold. In 108 patients (59 male; mean age: 57 ± 17y) the mean study time was 17 ± 3 min. An abnormal strain response after the breathing maneuver (persistent/increased/new onset of increased strain rates) correctly identified all 17 patients with a high-sensitivity troponin T dynamic (0 h/1 h algorithm) and explanatory significant coronary lesions, while in 86 patients without serologic or angiographic evidence for severe coronary artery disease the strain response was normal (sensitivity 100%, specificity 94.5%; 5 false positive results). The number of dysfunctional segments (strain > - 10%) proved to be a quantifiable marker for identifying patients with acute coronary syndrome. In patients with suspected acute coronary syndrome and inconclusive initial high-sensitivity troponin T, fast-strain-encoded imaging with a breathing maneuver may safely and rapidly identify patients with acute coronary syndrome, without the need for vasodilators, stress, or contrast agents.

Coronary Computed Tomography vs. Cardiac Magnetic Resonance Imaging in the Evaluation of Coronary Artery Disease.

Coronary artery disease (CAD) represents a widespread burden to both individual and public health, steadily rising across the globe. The current guidelines recommend non-invasive anatomical or functional testing prior to invasive procedures. Both coronary computed tomography angiography (cCTA) and stress cardiac magnetic resonance imaging (CMR) are appropriate imaging modalities, which are increasingly used in these patients. Both exhibit excellent safety profiles and high diagnostic accuracy. In the last decade, cCTA image quality has improved, radiation exposure has decreased and functional information such as CT-derived fractional flow reserve or perfusion can complement anatomic evaluation. CMR has become more robust and faster, and advances have been made in functional assessment and tissue characterization allowing for earlier and better risk stratification. This review compares both imaging modalities regarding their strengths and weaknesses in the assessment of CAD and aims to give physicians rationales to select the most appropriate modality for individual patients.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test.

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations. Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion. Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: -19.4 ± 1.9%, GLSDHE: -20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= -19.5 ± 2.3%, GLSDob= -19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001). Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Feasibility of fast cardiovascular magnetic resonance strain imaging in patients presenting with acute chest pain.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the current reference standard for the quantitative assessment of ventricular function. Fast Strain-ENCoded (fSENC)-CMR imaging allows for the assessment of myocardial deformation within a single heartbeat. The aim of this pilot study was to identify obstructive coronary artery disease (oCAD) with fSENC-CMR in patients presenting with new onset of chest pain. METHODS AND RESULTS: In 108 patients presenting with acute chest pain, we performed fSENC-CMR after initial clinical assessment in the emergency department. The final clinical diagnosis, for which cardiology-trained physicians used clinical information, serial high-sensitive Troponin T (hscTnT) values and-if necessary-further diagnostic tests, served as the standard of truth. oCAD was defined as flow-limiting CAD as confirmed by coronary angiography with typical angina or hscTnT dynamics. Diagnoses were divided into three groups: 0: non-cardiac, 1: oCAD, 2: cardiac, non-oCAD. The visual analysis of fSENC bull´s eye maps (blinded to final diagnosis) resulted in a sensitivity of 82% and specificity of 87%, as well as a negative predictive value of 96% for identification of oCAD. Both, global circumferential strain (GCS) and global longitudinal strain (GLS) accurately identified oCAD (area under the curve/AUC: GCS 0.867; GLS 0.874; p<0.0001 for both), outperforming ECG, hscTnT dynamics and EF. Furthermore, the fSENC analysis on a segmental basis revealed that the number of segments with impaired strain was significantly associated with the patient´s final diagnosis (p<0.05 for all comparisons). CONCLUSION: In patients with acute chest pain, myocardial strain imaging with fSENC-CMR may serve as a fast and accurate diagnostic tool for ruling out obstructive coronary artery disease.

No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after More than 20 Serial Injections of Macrocyclic Gadolinium-based Contrast Agents.

Purpose To determine the effect of more than 20 serial injections of macrocyclic gadolinium-based contrast agents (GBCAs) on the signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 33 patients who underwent at least 20 consecutive MR imaging examinations (plus an additional MR imaging for reference) with the exclusive use of macrocyclic GBCAs gadoterate meglumine and gadobutrol were analyzed. SI ratio differences were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios by subtracting the SI ratio at the first MR imaging examination from the SI ratio at the last MR imaging examination. One-sample t tests were used to examine if the SI ratio differences differed from 0, and Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 23.03 ± (standard deviation) 4.20 GBCA administrations (mean accumulated dose, 491.21 mL ± 87.04 of a 0.5 M GBCA solution) with an average of 12.09 weeks ± 2.16 between every administration. Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0032 ± 0.0154, P = .248; DN-to-MCP ratio: -0.0011 ± 0.0093, P = .521), and one-sided Bayes factors provided substantial to strong evidence against an SI ratio increase (Bayes factor for DN-to-pons ratio = 0.09 and that for DN-to-MCP ratio = 0.12). Conclusion The study indicates that 20 or more serial injections of macrocyclic GBCAs administered with on average 3 months between each injection are not associated with an SI increase in the DN. © RSNA, 2016.

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PURPOSE: Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine. MATERIALS AND METHODS: Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods. RESULTS: The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011). CONCLUSIONS: In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.

High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol.

OBJECTIVE: The aim of this study was to compare changes in the signal intensity (SI) ratio of the dentate nucleus (DN) to the pons, DN to cerebrospinal fluid (CSF), and globus pallidus (GP) to thalamus on unenhanced T1-weighted magnetic resonance imaging (MRI) scans after serial injections of the macrocyclic gadolinium-based contrast agent gadobutrol. MATERIALS AND METHODS: Thirty patients who had received at least 5 MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobutrol, resulting in a total cumulative dose of 54.1 ± 30.4 mL gadobutrol, were analyzed retrospectively. Signal intensity ratio differences were calculated for DN-to-pons, DN-to-CSF, and GP-to-thalamus ratios by subtracting the SI ratio at the first MRI from the SI ratio at the last MRI scan. One-sample t tests were employed to examine if they differed from 0. Regression and correlational analyses were performed to examine whether the SI ratio differences were predicted by a number of control variables. RESULTS: Signal intensity ratio differences did not differ significantly from 0, neither for the DN-to-pons ratio (-0.0035 ± 0.0476, P = 0.69), the DN-to-CSF ratio (-0.0539 ± 0.3217, P = 0.37), nor the GP-to-thalamus ratio (-0.0020 ± 0.0211, P = 0.60). None of the control variables predicted changes in SI ratios. CONCLUSIONS: In contrast to a recently published study, we did not find signal increases in the DN or in the GP after serial injections of gadobutrol, even though the total dose applied here was considerably larger than in the respective study. This finding adds further support to the hypothesis that the molecular structure of a gadolinium-based contrast agent as either macrocyclic or linear is a crucial factor for its potential to cause gadolinium deposition in the brain. Future studies should further assess this hypothesis by additional animal investigations as well as histopathological and clinical correlation studies.

Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration.

OBJECTIVES: The aim of this study was to compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) to pons and cerebrospinal fluid (CSF) on unenhanced T1-weighted magnetic resonance imaging (MRI) scans between the first and last MRI using the linear gadolinium-based contrast agent gadobenate dimeglumine. MATERIALS AND METHODS: The study was approved by the ethical committee of the University of Heidelberg (S-324/2014), and written informed consent was waived due to the retrospective character of the study. Fifty patients who underwent at least 5 consecutive MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobenate dimeglumine were analyzed retrospectively. The difference of DN-to-pons and DN-to-CSF mean SI ratios was calculated on unenhanced T1-weighted images between the first and last examination. Results were compared with previously published data on gadopentetate dimeglumine and gadoterate meglumine. RESULTS: Signal intensity ratio differences for DN-to-pons and DN-to-CSF were significantly greater than 0 (pons: 0.0399 ± 0.0307, P < 0.001; CSF: 0.1439 ± 0.1524, P < 0.001). No control variable consistently predicted the SI ratio difference for the DN-to-pons and the DN-to-CSF ratio. Compared with previously published data, the difference in SI increase between gadopentetate dimeglumine and gadobenate dimeglumine was not significant for the DN-to-pons ratio (P = 0.906). In contrast, the DN-to-CSF ratio difference was significantly lower (P < 0.001) for gadobenate dimeglumine. Dentate nucleus-to-pons (P < 0.001) and DN-to-CSF (P = 0.017) ratio differences were both significantly higher for gadobenate dimeglumine than for gadoterate meglumine. CONCLUSIONS: The present study found an increase in SI in the DN after serial injections of gadobenate dimeglumine. Further studies are needed to clarify the potential of different linear gadolinium-based contrast agents to cause SI increase in the DN.

Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent.

PURPOSE: To compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) and the globus pallidus (GP) to those of other structures on unenhanced T1-weighted magnetic resonance (MR) images between linear and macrocyclic gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: The study was approved by the ethical committee of the University of Heidelberg (reference no. S-324/2014). Owing to the retrospective character of the study, the ethical committee did not require any written informed consent. Two groups of 50 patients who underwent at least six consecutive MR imaging examinations with the exclusive use of either a linear GBCA (gadopentetate dimeglumine) or a macrocyclic GBCA (gadoterate meglumine) were analyzed retrospectively. The difference in mean SI ratios of DN to pons and GP to thalamus on unenhanced T1-weighted images from the last and first examinations was calculated. One-sample and independent-sample t tests were used to assess the difference in SI ratios for both groups, and regression analysis was performed to account for potential confounders. RESULTS: The SI ratio difference in the linear group was greater than 0 (mean DN difference ± standard deviation, 0.0407 ± 0.0398 [P < .001]; GP, 0.0287 ± 0.0275 [P < .001]) and significantly larger (DN, P < .001 and standardized difference of 1.16; GP, P < .001 and standardized difference of 0.81) than that in the macrocyclic group, which did not differ from 0 (DN, 0.0016 ± 0.0266 [P = .680]; GP, 0.0031 ± 0.0354 [P = .538]). The SI ratio difference between the last and first examinations for the DN remained significantly different between the two groups in the regression analysis (P < .001). CONCLUSION: This study indicates that an SI increase in the DN and GP on T1-weighted images is caused by serial application of the linear GBCA gadopentetate dimeglumine but not by the macrocyclic GBCA gadoterate meglumine. Clinical implications of this observation remain unclear.