Feasibility of Reduced Iodine Loads for Vascular Assessment Prior to Transcatheter Aortic Valve Implantation (TAVI) Using Spectral Detector CT.

Reduced iodine loads for computed tomography (CT)-based vascular assessment prior to transcatheter aortic valve implantation (TAVI) may be feasible in conjunction with a spectral detector CT scanner. This prospective single-center study considered 100 consecutive patients clinically referred for pre-TAVI CT. They were examined on a dual-layer detector CT scanner to obtain an ECG-gated cardiac scan and a non-ECG-gated aortoiliofemoral scan. Either a standard contrast media (SCM) protocol using 80 mL Iohexol 350 mgI/mL (iodine load: 28 gI) or a body-mass-index adjusted reduced contrast media (RCM) protocol using 40-70 mL Iohexol 350 mgI/mL (iodine load: 14-24.5 gI) were employed. Conventional images and virtual monoenergetic images at 40-80 keV were reconstructed. A threshold of 250 HU was set for sufficient attenuation along the arterial access pathway. A qualitative assessment used a five-point Likert scale. Sufficient attenuation in the thoracic aorta was observed for all patients in both groups using conventional images. In the abdominal, iliac, and femoral segments, sufficient attenuation was observed for the majority of patients when using virtual monoenergetic images (SCM: 96-100% of patients, RCM: 88-94%) without statistical difference between both groups. Segments with attenuation measurements below the threshold remained qualitatively assessable as well. Likert scores were 'excellent' for virtual monoenergetic images 50 keV and 55 keV in both groups (RCM: 1.2-1.4, SCM: 1.2-1.3). With diagnostic image quality maintained, it can be concluded that reduced iodine loads of 14-24.5 gI are feasible for pre-TAVI vascular assessment on a spectral detector CT scanner.

Reproducibility assessment of rapid strains in cardiac MRI: Insights and recommendations for clinical application.

PURPOSE: Studies have shown the incremental value of strain imaging in various cardiac diseases. However, reproducibility and generalizability has remained an issue of concern. To overcome this, simplified algorithms such as rapid atrioventricular strains have been proposed. This multicenter study aimed to assess the reproducibility of rapid strains in a real-world setting and identify potential predictors for higher interobserver variation. METHODS: A total of 4 sites retrospectively identified 80 patients and 80 healthy controls who had undergone cardiac magnetic resonance imaging (CMR) at their respective centers using locally available scanners with respective field strengths and imaging protocols. Strain and volumetric parameters were measured at each site and then independently re-evaluated by a blinded core lab. Intraclass correlation coefficients (ICC) and Bland-Altman plots were used to assess inter-observer agreement. In addition, backward multiple linear regression analysis was performed to identify predictors for higher inter-observer variation. RESULTS: There was excellent agreement between sites in feature-tracking and rapid strain values (ICC ≥ 0.96). Bland-Altman plots showed no significant bias. Bi-atrial feature-tracking and rapid strains showed equally excellent agreement (ICC ≥ 0.96) but broader limits of agreement (≤18.0 % vs. ≤3.5 %). Regression analysis showed that higher field strength and lower temporal resolution (>30 ms) independently predicted reduced interobserver agreement for bi-atrial strain parameters (ß = 0.38, p = 0.02 for field strength and ß = 0.34, p = 0.02 for temporal resolution). CONCLUSION: Simplified rapid left ventricular and bi-atrial strain parameters can be reliably applied in a real-world multicenter setting. Due to the results of the regression analysis, a minimum temporal resolution of 30 ms is recommended when assessing atrial deformation.

Effects of Ionizing Radiation on Cardiac Implantable Electronic Devices (CIEDs) in Patients with Esophageal Cancer Undergoing Radiotherapy: A Pilot Study.

(1) Background: The prevalence of cancer patients relying on cardiac implantable electronic device (CIED) is steadily rising. The aim of this study was to evaluate RT-related malfunctions of CIEDs. (2) Methods: We retrospectively analyze sixteen patients with esophageal cancer who were treated with radiotherapy between 2012 and 2022 at the University Hospital Heidelberg. All patients underwent systemic evaluation including pre-therapeutic cardiological examinations of the CIED functionality and after every single irradiation. (3) Results: Sixteen patients, predominantly male (14) with a mean age of 77 (range: 56-85) years were enrolled. All patients received 28 fractions of radiotherapy with a cumulative total dose 58.8 Gy. The mean maximum dose at the CIEDs was 1.8 Gy. Following radiotherapy and during the one-year post-radiation follow-up period, there were no registered events associated with the treatment in this evaluation. (4) Conclusion: The study did not observe any severe CIED malfunctions following each radiation fraction or after completion of RT. Strict selection of photon energy and alignment with manufacturer-recommended dose limits appear to be important. Our study showed no major differences in the measured values of the pacing threshold, sensing threshold and lead impedance after RT.

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.

Absence of visible infarction on cardiac magnetic resonance imaging despite the established diagnosis of myocardial infarction by 4th Universal Definition of Myocardial Infarction.

AIMS: Myocardial scarring due to acute myocardial infarction (AMI) can be visualized by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. However, a recent study revealed a group of Type 1 AMI patients with undetectable myocardial injury on LGE. This study aims to describe these cases in detail and explore possible explanations for this new phenomenon. METHODS AND RESULTS: A total of 137 patients diagnosed with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (non-STEMI) diagnosed according to the 4th Universal Definition of Myocardial Infarction underwent LGE-CMR after invasive coronary angiography. Fourteen of them (10.2%) showed no LGE and were included in the final study population. Most patients presented with acute chest pain, 3 patients were diagnosed as STEMI, and 11 as non-STEMI. Peak high-sensitive cardiac troponin T ranged from 45 to 1173 ng/L. A culprit lesion was identified in 12 patients. Severe coronary stenoses were found in five patients, while seven patients had subtotal to total coronary artery occlusion. Percutaneous coronary intervention was performed in 10 patients, while 2 patients required coronary artery bypass grafting and no intervention was required in 2 patients. Cardiac magnetic resonance was performed 30 (4-140) days after the initial presentation. Most patients showed preserved left ventricular ejection fraction on CMR. No alternative reasons for the rise/fall of high-sensitive cardiac troponin T were found. CONCLUSION: The absence of LGE on CMR in patients with Type 1 AMI is a new finding. While insufficient spatial resolution of LGE imaging, delayed CMR performance, spontaneous reperfusion, and coronary collaterals may provide some explanations, further investigations are required to fully understand this phenomenon.

Prognostic value of negative stress cardiac magnetic resonance imaging in patients with moderate-severe coronary artery stenosis.

Objective: This study aims to evaluate the prognostic value of stress cardiac magnetic resonance (CMR) without inducible ischemia in a real-world cohort of patients with known severe coronary artery stenosis. Background: The prognosis of patients with severe coronary artery stenosis and without inducible ischemia using stress CMR remains uncertain, even though its identification of functionally significant coronary artery disease (CAD) is excellent. Materials and methods: Patients without inducible ischemia and known CAD who underwent stress CMR between February 2015 and December 2016 were included in this retrospective study. These patients were divided into two groups: group 1 with stenosis of 50%-75% and group 2 with stenosis of >75%. The primary endpoint was defined as the occurrence of a major adverse cardiovascular event (MACE) [cardiac death, non-fatal myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Results: Real-world data collected from 169 patients with a median age of 69 (60-75) years were included. The median follow-up was 5.5 (IQR 4.1-6.6) years. Events occurred after a mean time of 3.0 ± 2.2 years in group 1 and 3.7 ± 2.0 years in group 2 (p = 0.35). Sixteen (18.8%) patients in group 1 and 23 (27.4%) patients in group 2 suffered from MACE without a significant difference between the two groups (p = 0.33). In group 2, one cardiac death (1.2%), seven non-fatal MI (8.3%), 15 PCI (17.9%), and one CABG (1.2%) occurred. Conclusion: The findings of this pilot study suggest that long-term outcomes in a real-world patient cohort with known severe and moderate coronary artery stenosis but without inducible ischemia were similar. Stress CMR may provide valuable risk stratification in patients with angiographically significant but hemodynamically non-obstructive coronary lesions.

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.

Safety of Stress Cardiac Magnetic Resonance in Patients With Moderate to Severe Aortic Valve Stenosis.

BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.

Correlation of serial high-sensitivity cardiac Troponin T values to infarct mass determined by cardiac magnetic resonance imaging: a validation study.

AIM: To validate correlations between contrast-enhanced magnetic resonance imaging (CE-MRI) infarct mass and high-sensitivity cardiac Troponin T (hs-cTnT) values at different time points in patients with confirmed acute myocardial infarction (AMI). METHODS AND RESULTS: Patients presenting with AMI and with available CE-MRI between 1 January 2018 and 31 December 2020 were included. Correlation coefficients between hs-cTnT on admission, after 24, 48, 72, and 96 h, and peak hs-cTnT values and CE-MRI infarct mass were calculated. Correlations between hs-cTnT and CE-MRI infarct mass were compared with those of a third generation cTnT assay from a previously published study of our group. A total of 137 patients were included for the present analysis. Median CE-MRI infarct mass was 12,5 g [95% confidence interval (CI): 9.8-16.2 g]. Hs-cTnT values and infarct mass correlated well at all time points including admission (r = 0.474, 95% CI: 0.331-0.560, P < 0.0001), 24 h (r = 0.508, 95% CI: 0.370-0.625, P < 0.0001), 48 h (r = 0.547, 95% CI: 0.404-0.664, P < 0.0001), 72 h (r = 0.489, 95% CI: 0.320-0.628, P < 0.0001), 96 h (r = 0.509, 95% CI: 0.330-0.653, P < 0.001) including peak hs-cTnT values (r = 0.547, 95% CI: 0.416-0.656, P < 0.0001), and maximum absolute delta changes within 96 h (r = 0.507, 95% CI: 0.369-0.622, P < 0.001). Correlations of the third generation assay could be confirmed for hs-cTnT at all time points. A superior correlation with CE-MRI infarct mass was observed for hs-cTnT values on admission. CONCLUSION: Hs-cTnT values at different time points correlate well with CE-MRI infarct mass. Correlations of admission hs-cTnT values are superior to those of a third generation assay.

A head-to-head comparison of fast-SENC and feature tracking to LV long axis strain for assessment of myocardial deformation in chest pain patients.

BACKGROUND: Myocardial strain imaging has gained importance in cardiac magnetic resonance (CMR) imaging in recent years as an even more sensitive marker of early left ventricular dysfunction than left-ventricular ejection fraction (LVEF). fSENC (fast strain encoded imaging) and FT (feature tracking) both allow for reproducible assessment of myocardial strain. However, left-ventricular long axis strain (LVLAS) might enable an equally sensitive measurement of myocardial deformation as global longitudinal or circumferential strain in a more rapid and simple fashion. METHODS: In this study we compared the diagnostic performance of fSENC, FT and LVLAS for identification of cardiac pathology (ACS, cardiac-non-ACS) in patients presenting with chest pain (initial hscTnT 5-52 ng/l). Patients were prospectively recruited from the chest pain unit in Heidelberg. The CMR scan was performed within 1 h after patient presentation. Analysis of LVLAS was compared to the GLS and GCS as measured by fSENC and FT. RESULTS: In total 40 patients were recruited (ACS n = 6, cardiac-non-ACS n = 6, non-cardiac n = 28). LVLAS was comparable to fSENC for differentiation between healthy myocardium and myocardial dysfunction (GLS-fSENC AUC: 0.882; GCS-fSENC AUC: 0.899; LVLAS AUC: 0.771; GLS-FT AUC: 0.740; GCS-FT: 0.688), while FT-derived strain did not allow for differentiation between ACS and non-cardiac patients. There was significant variability between the three techniques. Intra- and inter-observer variability (OV) was excellent for fSENC and FT, while for LVLAS the agreement was lower and levels of variability higher (intra-OV: Pearson > 0.7, ICC > 0.8; inter-OV: Pearson > 0.65, ICC > 0.8; CoV > 25%). CONCLUSIONS: While reproducibility was excellent for both FT and fSENC, it was only fSENC and the LVLAS which allowed for significant identification of myocardial dysfunction, even before LVEF, and therefore might be used as rapid supporting parameters for assessment of left-ventricular function.

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.

Dual-Layer Spectral CTA for TAVI Planning Using a Split-Phase Protocol and Low-keV Virtual Monoenergetic Images: Improved Image Quality in Comparison with Single-Phase Conventional CTA.

PURPOSE: Adaptation of computed tomography protocols for transcatheter aortic valve implantation (TAVI) planning is required when a first-generation dual-layer spectral CT scanner (DLCT) is used. The purpose of this study was to evaluate the objective image quality of aortic CT angiography (CTA) for TAVI planning using a split-phase technique with reconstruction of 40 keV virtual monoenergetic images (40 keV-VMI) obtained with a DLCT scanner. CT angiography obtained with a single-phase protocol of a conventional single-detector CT (SLCT) was used for comparison. MATERIALS AND METHODS: 75 CTA scans from DLCT were retrospectively compared to 75 CTA scans from SLCT. For DLCT, spiral CTA without ECG-synchronization was performed immediately after a retrospectively ECG-gated acquisition covering the heart and aortic arch. For SLCT, spiral CTA with retrospective ECG-gating was performed to capture the heart and the access route simultaneously in one scan. Objective image quality was compared at different levels of the arterial access route. RESULTS: 40 keV virtual monoenergetic images of DLCT showed a significantly higher mean vessel attenuation, SNR, and CNR at all levels of the arterial access route. With 40 keV-VMI of DLCT, the overall mean aortic attenuation of all six measured regions was 589.6 ±â€Š243 HU compared to 492.7 ±â€Š209 HU of SLCT (p < 0.01). A similar trend could be observed for SNR (23.6 ±â€Š18 vs. 18.6 ±â€Š9; p < 0.01) and CNR (21.1 ±â€Š18 vs. 16.4 ±â€Š8; p < 0.01). No deterioration was observed for vascular noise (27.8 ±â€Š9 HU vs. 28.1 ±â€Š8 HU; p = 0.599). CONCLUSION: Using a DLCT scanner with a split-phase protocol and 40 keV-VMI for TAVI planning, higher objective image quality can be obtained compared to a single-phase protocol of a conventional CT scanner. KEY POINTS: · Adaption of TAVI planning CT protocols may be required when using a first-generation dual-layer CT scanner.. · Reconstruction of virtual monoenergetic images at 40 keV improves image quality.. · With a split-phase protocol, the radiation dose is lower compared to a single-phase ECG-gated CT acquisition.. CITATION FORMAT: · Mangold D, Salatzki J, Riffel J et al. Dual-Layer Spectral CTA for TAVI Planning Using a Split-Phase Protocol and Low-keV Virtual Monoenergetic Images: Improved Image Quality in Comparison with Single-Phase Conventional CTA. Fortschr Röntgenstr 2022; 194: 652 - 659.

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.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Comparative Transcriptomics of Immune Checkpoint Inhibitor Myocarditis Identifies Guanylate Binding Protein 5 and 6 Dysregulation.

Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing use leads to an increase of immune-related adverse events (irAEs). Among them, ICI-associated myocarditis (ICIM) is a rare irAE with a high mortality rate. We aimed to characterize the transcriptional changes of ICIM myocardial biopsies and their possible implications. Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n = 9) with samples from dilated cardiomyopathy (DCM, n = 11), virus-induced myocarditis (VIM, n = 5), and with samples of patients receiving ICIs without any evidence of myocarditis (n = 4). Patients with ICIM (n = 19) showed an inconsistent clinical presentation, e.g., asymptomatic elevation of cardiac biomarkers (hs-cTnT, NT-proBNP, CK), a drop in left ventricular ejection fraction, or late gadolinium enhancement in cMRI. We found 3784 upregulated genes in ICIM (FDR < 0.05). In the overrepresented pathway 'response to interferon-gamma', we found guanylate binding protein 5 and 6 (compared with VIM: GBP5 (log2 fc 3.21), GBP6 (log2 fc 5.37)) to be significantly increased in ICIM on RNA- and protein-level. We conclude that interferon-gamma and inflammasome-regulating proteins, such as GBP5, may be of unrecognized significance in the pathophysiology of ICIM.

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.

Hyperventilation/Breath-Hold Maneuver to Detect Myocardial Ischemia by Strain-Encoded CMR: Diagnostic Accuracy of a Needle-Free Stress Protocol.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH). BACKGROUND: Myocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations. METHODS: Patients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference. RESULTS: A total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p < 0.05) and territory level (adenosine-strain: sensitivity 67%, specificity 93%; HVBH-strain: sensitivity 63%, specificity 95% vs. adenosine-perfusion: sensitivity 49%, specificity 96%; p < 0.05). However, these differences in diagnostic accuracy disappear by excluding patients with history of coronary artery bypass graft or previous myocardial infarction. The response of longitudinal strain differs significantly between ischemic and nonischemic segments to adenosine (ΔLSischemic = 0.6 ± 5.4%, ΔLSnonischemic = -0.9 ± 2.7%; p < 0.05) and HVBH (ΔLSischemic = 1.3% ± 3.8%, ΔLSnonischemic = -0.3 ± 1.8%; p = 0.002). Test duration of HVBH-strain (t = 64 ± 2 s) was significantly shorter compared with adenosine-strain (t = 184 ± 59 s; p < 0.0001) and adenosine-perfusion (t = adenosine-perfusion: 172 ± 59 s; p < 0.0001). CONCLUSIONS: HVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block.

BACKGROUND: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. METHODS: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. RESULTS: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. CONCLUSIONS: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. TRIAL REGISTRATION: This study was retrospectively registered.

Spatial relationship between the pulmonary trunk and the left coronaries: Systematic risk assessment based on automated three-dimensional distance measurements.

BACKGROUND: Catheter ablation of right ventricular outflow tract ventricular arrhythmias from above the pulmonary valve is being increasingly reported. OBJECTIVE: The purpose of this study was to systematically analyze the spatial relationship between the pulmonary trunk and the left coronaries. METHODS: Contrast-enhanced computed tomographic scans from 58 patients were analyzed. After segmentation of the pulmonary trunk and the proximal left coronaries, 3-dimensional geometries were generated. Minimal distance between the pulmonary trunk and the coronaries was automatically determined using a newly developed mathematical algorithm. RESULTS: The minimal distance between the pulmonary trunk and the coronaries was 1.4 ± 0.11 mm. Closest relationship was detected 13.8 ± 0.87 mm above the pulmonary valve annulus. Considering a safety margin of 5 mm to render coronary damage unlikely, 84% of patients were found to be at potential risk within the bottom 10 mm of the left sinus cusp. In contrast, positions within or above the right and anterior cusps were less likely to exhibit a close relationship. We identified the anterior aspect of the left cusp as the most critical region. Positions 10-20 mm above the left cusp were found to be critical in 97% of patients. Clinical parameters such as gender, age, height, weight, and body mass index were not predictive of a close spatial relationship. CONCLUSION: Our data provide evidence for a close spatial relationship between the pulmonary trunk and coronary arteries. These results should be considered when performing catheter ablation from above the pulmonary valve.