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.

Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

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.

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.

Feasibility and Challenges of Transcatheter Edge-to-Edge Repair for Very Large Tricuspid Valve Gaps.

Massive and torrential tricuspid regurgitation may be accompanied by very large gaps, posing a challenge for transcatheter edge-to-edge repair (TEER). These 2 cases involve patients who underwent successful TEER despite very large gaps. Both patients experienced significant improvement after TEER. Feasibility and challenges of TEER in very large gaps are presented. (Level of Difficulty: Advanced.).

Metabolic Effect of Blocking Sodium-Taurocholate Co-Transporting Polypeptide in Hypercholesterolemic Humans with a Twelve-Week Course of Bulevirtide-An Exploratory Phase I Clinical Trial.

Bile acids (BA) play an important role in cholesterol metabolism and possess further beneficial metabolic effects as signalling molecules. Blocking the hepatocellular uptake of BA via sodium-taurocholate co-transporting polypeptide (NTCP) with the first-in-class drug bulevirtide, we expected to observe a decrease in plasma LDL cholesterol. In this exploratory phase I clinical trial, volunteers with LDL cholesterol > 130 mg/dL but without overt atherosclerotic disease were included. Thirteen participants received bulevirtide 5 mg/d subcutaneously for 12 weeks. The primary aim was to estimate the change in LDL cholesterol after 12 weeks. Secondary endpoints included changes in total cholesterol, HDL cholesterol, lipoprotein(a), inflammatory biomarkers, and glucose after 12 weeks. In addition, cardiac magnetic resonance imaging (CMR) was performed at four time points. BA were measured as biomarkers of the inhibition of hepatocellular uptake. After 12 weeks, LDL cholesterol decreased not statistically significantly by 19.6 mg/dL [−41.8; 2.85] (Hodges−Lehmann estimator with 95% confidence interval). HDL cholesterol showed a significant increase by 5.5 mg/dL [1.00; 10.50]. Lipoprotein(a) decreased by 1.87 mg/dL [−7.65; 0]. Inflammatory biomarkers, glucose, and cardiac function were unchanged. Pre-dose total BA increased nearly five-fold (from 2026 nmol/L ± 2158 (mean ± SD) at baseline to 9922 nmol/L ± 7357 after 12 weeks of treatment). Bulevirtide was generally well tolerated, with most adverse events being administration site reactions. The exploratory nature of the trial with a limited number of participants allows the estimation of potential effects, which are crucial for future pharmacological research on bile acid metabolism in humans.

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.

Homoarginine treatment of rats improves cardiac function and remodeling in response to pressure overload.

Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n = 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4 weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg-1 ·day-1 . Combining 800 mg·kg-1 ·day-1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p = 0.0002) and fractional shortening (+41%, p = 0.0014). An inverse association was observed with collagen area fraction (-41%, p < 0.0001), myocyte cross-sectional area (-22%, p < 0.0001) and the molecular markers atrial natriuretic factor (-74%, p = 0.0091), brain natriuretic peptide (-42%, p = 0.0298), beta-myosin heavy chain (-46%, p = 0.0411), and collagen type V alpha 1 chain (-73%, p = 0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology.

Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure.

PURPOSE: Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx). METHODS: A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg-1·day-1 HA over a 4-week period. RESULTS: 5/6 Nx per se resulted in adverse myocardial remodeling with aggravated cardiac function and associated cardiac overload as the most obvious alteration (-23% ejection fraction, P < 0.0001), as well as increased myocardial fibrosis (+80%, P = 0.0005) compared to placebo treated sham animals. HA treatment of 5/6 Nx rats has led to an improvement of ejection fraction (+24%, P = 0.0003) and fractional shortening (+21%, P = 0.0126), as well as a decrease of collagen deposition (-32%, P = 0.0041), left ventricular weight (-14%, P = 0.0468), and myocyte cross-sectional area (-12%, P < 0.0001). These changes were accompanied by a downregulation of atrial natriuretic factor (-65% P < 0.0001) and collagen type V alpha 1 chain (-44%, P = 0.0006). Sham animals revealed no significant changes in cardiac function, myocardial fibrosis, or any of the aforementioned molecular changes after drug treatment. CONCLUSION: Dietary HA supplementation appears to have the potential of preventing cardiac remodeling and improving heart function in the setting of chronic kidney disease. Our findings shed new light on HA as a possible new therapeutic agent for patients at high cardiovascular risk.

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.

Myocardial mechanics in dilated cardiomyopathy: prognostic value of left ventricular torsion and strain.

BACKGROUND: Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). METHODS: CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. RESULTS: GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0-5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups. CONCLUSION: LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

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.

Age- and gender-related reference values of cardiac morphology and function in cardiovascular magnetic resonance.

Cardiovascular magnetic resonance (CMR) is the reference standard for the quantitative assessment of cardiac morphology and function. The aim of the study was to determine age- and gender-related reference values for cardiac morphology and function according to current recommendations. 454 healthy volunteers (235 men, median age 52.0 (44.0-59.0) years) underwent a standard CMR scan and were divided into six groups of nearly equal size with regard to sex (male, female) and age (21-47 years, 48-57 years, 58-84 years). Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were measured at end-diastole and end-systole in steady-state free precession series with including papillary muscles and trabecular tissue in the LV-M. Absolute and indexed volumetric parameters were significantly different between gender groups with higher values in men compared to women (all p < 0.001). Furthermore, a significant age-dependent decline could be observed for left ventricular and right ventricular volumes (all p < 0.001), while LV-M did not show differences between the different age-groups. Parameters of longitudinal function for the left and right ventricle were higher in female compared to male subjects with a significant age-dependent decline. We provided normal values for cardiac volumes, function, and mass derived in accordance with current guidelines from a large population of healthy subjects, which can be implemented in clinical routine as a standard of reference.

Appropriateness of CT pulmonary angiograms according to current diagnostic guidelines based on risk stratification: A retrospective single-center study.

BACKGROUND AND AIM: Assessment of appropriateness of CT pulmonary angiograms (CTPA) in patients with suspected pulmonary embolism (PE) is based on risk stratification algorithms such as simplified the Geneva Score (sGS) in combination with D-dimer blood tests. The aim of this study was to validate the diagnostic yield and appropriateness of CTPA examinations in accordance with 2014 European Society of Cardiology (ESC) guidelines. MATERIALS AND METHODS: Data from 155 outpatients who underwent CTPA for clinical suspicion of PE were gathered from the radiology information system (RIS) and the clinical information system (CIS). We assessed the presence of sGS items and D-dimer blood test results in RIS from CTPA request forms and from clinical documentation in CIS. RESULTS: Based on the RIS, there were 2.6% patients with high (sGS≥3) and 97.4% patients with low pre-test PE probability (sGS<3), and CTPA indication was formally comprehendible in 75.5% using sGS and D-dimer blood tests. Based on RIS and CIS data in combination, there were 41.3% patients with high and 58.7% patients with low pre-test PE probability, and CTPA indication was formally comprehendible in 88.4%. Using RIS and CIS in combination, PE probability was upgraded from low to high probability in 39.7% compared with RIS alone. In 12.9%, there was a lack of data in RIS for CTPA justification. CONCLUSION: There is a high diagnostic yield when applying current diagnostic guidelines to our data. There was however a notable discrepancy between the data transferred to the CTPA request forms from the full clinical documentation, therefore not readily available for clinical decision making.