High-dose dobutamine stress steady-state free precession (SSFP) cine MRI at 3T with patient adaptive local radiofrequency (RF) shimming using dual-source RF transmission.

PURPOSE: To prospectively assess the feasibility, image quality, and diagnostic accuracy of high-dose dobutamine stress magnetic resonance imaging (DSMR) using steady-state free precession (SSFP) cine imaging at 3T applying a dual-source radiofrequency (RF) excitation magnetic resonance imaging (MRI) system with parallel transmission and patient adaptive local RF shimming. MATERIALS AND METHODS: DSMR using SSFP cine imaging was performed in 44 patients at 3T scheduled for a clinically indicated coronary angiography. The effect of conventional versus dual-source RF transmission was assessed regarding homogeneity of the B1 field, contrast-to-noise ratios (CNRs) at rest, image quality, and diagnostic accuracy of DSMR using long and short axis. RESULTS: The mean percentage of the intended flip angle within the heart increased from 88 ± 9.1% with single-source to 103 ± 5.6% (P < 0.001) dual-source RF transmission. CNR increased for dual-source particularly at the apex (63.4 ± 24.2 vs. 36.5 ± 16.5, P < 0.001) but also at the base of the left ventricle (LV) (50.1 ± 14.8 vs. 39.3 ± 15.8, P < 0.001). Image quality of dual-source was higher both at rest (2.8 ± 0.5 vs. 2.6 ± 0.7, P < 0.001) and stress (2.5 ± 0.7 vs. 2.0 ± 1.0, P < 0.001). The number of segments with severe artifacts or nondiagnostic image quality at stress was lower with dual-source RF transmission (8% vs. 27%, P < 0.001). The diagnostic accuracy of DSMR in coronary territories using dual-source RF transmission was significantly higher (77% vs. 65%, P = 0.04). CONCLUSION: Patient adaptive local RF shimming using dual-source RF transmission provided significantly improved image quality and higher diagnostic accuracy of SSFP during DSMR at 3T compared to conventional RF transmission.

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial.

AIMS: Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension. METHODS AND RESULTS: Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508). CONCLUSIONS: Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

Value of additional strain analysis with feature tracking in dobutamine stress cardiovascular magnetic resonance for detecting coronary artery disease.

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) has been established for the detection of coronary artery disease (CAD). The novel technique feature tracking (FT) analyses left ventricular circumferential strain (Ecc) thus offering detailed information about myocardial deformation. The purpose of this study was to evaluate FT based Ecc for the detection of myocardial ischemia during DS-CMR. METHODS: A total of 25 patients (18 males; mean age 64 ± 10 years) with suspected or known CAD underwent a standardized high-dose DS-CMR protocol at 1.5 T. For FT analysis cine short axis (SAX) views (apical, medial, basal) at rest and during maximum dobutamine stress were used. None of the patients had wall motion abnormalities (WMAs) or impaired left ventricular function at rest or scar tissue. For analysis of Ecc the three SAX planes were divided into 16 segments (n = 400 segments). During stress 15 patients (34 segments) developed WMAs as assessed by visual analysis. All patients underwent x-ray coronary angiography for clinical reasons which served as the reference standard. Patients without WMAs during DS-CMR and exclusion of stenotic CAD were defined as normal (10 patients, 160 segments). In patients with significant CAD segments that were supplied by a vessel of >70% narrowing were defined as stenotic (n = 64). The remaining segments in patients with significant CAD were considered as remote (n = 176). RESULTS: At rest no differences in Ecc were observed between normal, stenotic and remote segments. High-dose dobutamine stress revealed highly significant differences between Ecc of normal and stenotic segments (p < 0.001), as well as between remote and stenotic segments (p < 0.001). The same observation took place for the absolute change of Ecc (p < 0.001 and p = 0.01). ROC analysis of Ecc during maximum DS-CMR differentiated normal from stenotic segments with a sensitivity of 75% and specificity of 67% using a cutoff -33.2% with an area under the curve of 0.78. Additional analysis of intermediate-dose dobutamine also showed a significant difference between normal and stenotic segments (p = 0.001). CONCLUSION: FT based analysis of Ecc during intermediate- and high-dose DS-CMR was feasible and differentiated between stenotic, remote and normal segments. Quantitative assessment of Ecc with FT may improve the diagnostic accuracy of DS-CMR for detection of ischemia.

Comparison of myocardial tagging and feature tracking in patients with severe aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve implantation (TAVI) has become an effective treatment for severe aortic stenosis (AS) in patients considered to be at high surgical risk. However, data relating to myocardial function and deformation in these patients are rare. Cardiovascular magnetic resonance (CMR) tagging has been established as non-invasive technique for the accurate measurement of myocardial motion. However, additional tagging datasets are necessary and the post-processing procedure is time-consuming. Recently, the novel technique of feature tracking (FT) was introduced, with which myocardial strain can be derived directly from balanced steady-state free precession (bSSFP) cine sequences. The study aim was to compare tagging with FT in patients with high-grade AS and who had been considered for TAVI. METHODS: Thirty patients with severe AS underwent cardiac magnetic resonance imaging at 1.5 T (Philips Achieva). A stack of serial short-axis slices was used to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LV mass and function. TomTec 2D Cardiac Performance Analysis software was used to derive myocardial deformation parameters from three short-axis cine views (basal, medial and apical levels) using bSSFP. All patients also underwent myocardial tagging on identical short-axis views, and data acquired from FT and tagging were compared. RESULTS: The mean left ventricular ejection fraction (LVEF), LVEDV and LVESV (57 ± 14%, 158 ± 58 ml, and 74 ± 48 ml, respectively) were all normal. All patients demonstrated concentric hypertrophy of the left ventricle with an increased basal septal thickness (16 ± 3 mm), LV mass (126 ± 40 g) and indexed LV mass (68 ± 23 g/m2, papillary muscles excluded). Bland-Altman analysis revealed a reasonable agreement between basal and medial circumferential strain (cc), and a good correlation was observed between tagging and FT for the derived basal and medial cc (Pearson's correlation coefficient 0.83 for basal, 0.74 for medial). Basal rotation was impaired compared to previous studies in patients with AS, but medial and apical rotations were comparable. The apical peak diastolic rotation velocity was faster compared to earlier analyses. Rotation, peak systolic and end-diastolic rotation velocity did not demonstrate any correlation or acceptable agreement between FT and tagging. The inter-observer agreement as assessed by the intra- class correlation coefficient for FT showed good results for the cc (basal 0.94, medial 0.83, apical 0.75). CONCLUSION: To the present authors' knowledge, this is the first study to assess myocardial motion using tagging and FT in patients with AS prior to TAVI. A reasonable agreement was found for the basal and medial cc between both techniques. Estimated cc-values using FT were systematically higher than those with tagging, but this might have been due to the different techniques employed. Although FT is a promising method to assess cc, further studies including the evaluation of standard values--and investigations with different diseases are necessary.

Mid- to long-term cardiac magnetic resonance findings in elite athletes recovered from COVID-19: results from an ongoing observational COVID-19 study at a German Olympic medical centre.

INTRODUCTION: The cardiac magnetic resonance (CMR) data on mid- to long-term myocardial damage due to COVID-19 infections in elite athletes are scarce. Therefore, this study investigated the mid -to long-term consequences of myocardial involvement after a COVID-19 infection in elite athletes. MATERIALS AND METHODS: This study included 27 athletes at the German Olympic Centre North Rhine-Westphalia (NRW)/Rhineland with a confirmed previous COVID-19 infection between January 2020 and October 2021. The athletes were part of an ongoing observational COVID-19 study at the Institute of Cardiology and Sports Medicine Cologne at the German Sport University (DSHS).Nine healthy non-athletes with no prior COVID-19 illness served as controls. CMR was performed within a mean of 182 days (standard deviation [SD] 99) of the initial positive test result. RESULTS: CMR did not reveal any signs of acute myocarditis (according to the current Lake Louise criteria) or myocardial damage in any of the 26 elite athletes with previous COVID-19 infection. Of these athletes, 92% experienced a symptomatic course, and 54% reported symptoms lasting for more than 4 weeks. One male athlete was excluded from the analysis because CMR revealed an arrhythmogenic right ventricular cardiomyopathy (ARVC). Athletes had significantly enlarged left and right ventricle volumes and increased left ventricular myocardial mass in comparison to the healthy control group (LVEDVi 103.4 vs 91.1 ml/m2, p = 0.031; RVEDVi 104.1 vs 86.6 ml/m2, p = 0.007; LVMi 59.0 vs 46.2 g/m2, p = 0.002). Only two cases of elevated high-sensitivity-Troponin were documented; in one, the participant had previously engaged in high-intensity training, and in the other, CMR revealed a diagnosis of an arrhythmogenic cardiomyopathy. CONCLUSION: Our findings suggest that the risk for mid- to long-term myocardial damage is very low to negligible in elite athletes. Our results do not allow conclusions to be drawn regarding myocardial injury in the acute phase of infection nor about possible long-term myocardial effects in the general population.

Cardiac Magnetic Resonance Reveals Incipient Cardiomyopathy Traits in Adult Patients With Phenylketonuria.

Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age- and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, -29.9±4.2 % versus -32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV).

OBJECTIVES: Anti-neutrophil antibodies (ANCA)-associated vasculitides (AAV) comprise different forms of small vessel vasculitis characterised by B-cell driven autoimmune processes and endothelial cell activation. Aim of this study was to correlate markers of B- and endothelial cell activation with clinical manifestations of disease in AAV. METHODS: Consecutive serum samples of patients fulfilling the Chapel Hill Consensus Conference (CHCC) and American College of Rheumatology (ACR) criteria for AAV and healthy donors were used for the determination of ANCA, B-lymphocyte stimulator (BLyS), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) levels using enzyme-linked immunosorbent assay (ELISA). Subset and follow-up analyses were performed in cytoplasmatic ANCA (C-ANCA) or perinuclear ANCA (P-ANCA) positive patients with respect to change in ANCA-titres during the course of disease. RESULTS: Levels of sVCAM-1 were elevated in all patient groups with vasculitis compared to healthy controls. In contrast, significantly increased levels of BLyS were only observed in patients with Wegener's granulomatosis (WG), but not in patients with microscopic polyangiitis (mPAN)/Churg-Strauss-syndrome (CSS). Remarkably, there were no differences in the levels of sE-selectin between the vasculitis groups and healthy controls. In follow-up analysis, a significant correlation was shown for sE-Selectin and P-ANCA titres as well as sVCAM-1 levels. Furthermore, a strong correlation was detected for sVCAM-1 and creatinine levels. Interestingly, sE-selectin levels and C-ANCA titres were negatively correlated. CONCLUSIONS: Enhanced levels of sVCAM-1 represent a marker for endothelial cell activation in AAV. The observed correlation between sVCAM-1 and creatinine levels might indicate the influence of the vasculitic process on renal function. Signalling pathways for B-cells provided by BLyS could play a significant role in the pathogenesis of WG.

Assessment of Global Longitudinal and Circumferential Strain Using Computed Tomography Feature Tracking: Intra-Individual Comparison with CMR Feature Tracking and Myocardial Tagging in Patients with Severe Aortic Stenosis.

In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0 (Leiden, The Netherlands) software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 ± 5.04 vs. 22.40 ± 5.69, respectively; p = 0.065). GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS (r = 0.686, p < 0.001) and GCS (r = 0.707, p < 0.001), while both of these methods correlated moderately with TAG for GCS (r = 0.479, p < 0.001 for CMR-FT vs. TAG; r = 0.548 for CT-FT vs. TAG). Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG.

Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study.

AIM: To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. METHODS AND RESULTS: 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. CONCLUSIONS: RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress.

Cardiac magnetic resonance for prognostic assessment: present applications and future directions.

Cardiac magnetic resonance is increasingly used in clinical practice for both diagnostic and prognostic purposes. In the field of ischemic heart disease, perfusion imaging permits the assessment of ischemia, which is strongly related to future cardiac events and mortality. Late gadolinium enhancement is also associated with the prognosis and can be used as a marker of functional recovery. Cardiac magnetic resonance also permits the detection of microvascular obstruction and infarct hemorrhage, both related to an adverse outcome. In non-ischemic heart disease, the presence of late gadolinium enhancement is linked to mortality and hard events. Finally, coronary angiography, as well as new techniques, such as T1 mapping, may also have a prognostic role.

Potential reduction of interstitial myocardial fibrosis with renal denervation.

BACKGROUND: Hypertensive cardiomyopathy is characterized by myocyte hypertrophy and interstitial fibrosis. The effects of renal denervation (RD) on the heart are poorly understood. New magnetic resonance imaging techniques (extracellular volume fraction) permit the quantitative assessment of myocardial fibrosis. Our aim was to study the effects of RD on myocardial fibrosis. METHODS AND RESULTS: Twenty­three patients with resistant hypertension undergoing RD and 5 resistant hypertensive controls were prospectively included. Cardiac magnetic resonance imaging at 1.5 T was performed before RD and at 6­month follow­up. Indexed left ventricular mass, septal extracellular volume fraction, and indexed absolute extracellular volume (a quantitative measure of extracellular matrix) were quantified. All data are reported as mean±SD deviation (median). Decreases in systolic (161.96±19.09 [160] versus 144.78±16.48 [143] mm Hg, P<0.0001) and diastolic (85.61±12.88 [83] versus 80.39±11.93 [81] mm Hg, P=0.018) blood pressures and in indexed left ventricular mass (41.83±10.20 [41.59] versus 37.72±7.44 [38.49] g/m1.7, P=0.001) were observed at follow­up only in RD patients. No significant differences in extracellular volume were found (26.24±3.92% [26.06%] versus 25.74±4.53% [25.63%], P=0.605). A significant decrease in absolute extracellular volume was observed after 6 months in RD patients exclusively (10.36±2.25 [10.79] versus 9.25±2.38 [9.79] mL/m1.7, P=0.031). This effect was observed independently of blood pressure reduction. CONCLUSIONS: RD significantly decreases left ventricular mass, while extracellular volume remains stable. Our results suggest that the observed left ventricular mass decrease was due not exclusively to a reversion of myocyte hypertrophy but also to an additional reduction in collagen content, indicating interstitial myocardial fibrosis.

Magnetic resonance imaging of cardiovascular fibrosis and inflammation: from clinical practice to animal studies and back.

Late gadolinium enhancement is the technique of choice for detecting myocardial fibrosis. Although this technique is used in a wide range of cardiovascular pathologies, ischemic cardiomyopathy and the workup for myocarditis and other cardiomyopathies make up a significant proportion of the total indications. Multiple studies during the last decade have demonstrated its utility to adequately characterize myocardial tissue and offer diagnostic and prognostic information. Recent T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis. ¹9F magnetic resonance has recently emerged as a promising technique for the assessment of inflammation. In the following review we will discuss the basic aspects of fibrosis assessment with MR and its utility for diagnostic and prognostic evaluation. We will also address the topic of cardiovascular inflammation imaging with ¹9F as a potential new development that may broaden the indications for MR in the future.

Delayed contrast-enhanced MRI of the coronary artery wall in takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD. METHODS: We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34-45 minutes after low-dose gadolinium administration. RESULTS: No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474). CONCLUSION: Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.

Chronic CRP-exposure inhibits VEGF-induced endothelial cell migration.

UNLABELLED: C-reactive protein (CRP) is a pluripotent mediator of inflammation and is present at sites of vascular injury and in atherosclerotic lesions. CRP stimulates endothelial cell adhesion molecule expression and monocyte migration, thereby contributing to the development and progression of vascular lesion formation. In addition, chronic exposure to CRP is known to inhibit angiogenesis and endothelial cell (EC) proliferation. AIM: Whether CRP also affects EC migration, however, has yet to be determined. The present study investigates how long-term exposure to CRP interacts with vascular endothelial growth factor (VEGF) -induced EC migration. METHODS AND RESULTS: Using a Transwell chamber migration assay, VEGF (20 ng/mL, 5 h incubation)-induced migration of human umbilical vein EC was significantly inhibited in cells pretreated with CRP (10 microg/mL) for 24 h by more than 75%. EC migration in response to VEGF is known to require activation of the protein kinase B (Akt)/endothelial NO synthase (eNOS)- and the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway. We therefore investigated the long-term effects of CRP on these signalling events. Immunoblotting with phosphospecific antibodies revealed rapid and transient activation/phosphorylation of the protein kinase Akt within 20 minutes after stimulation with VEGF, which was inhibited by 86% in EC pretreated with CRP (10 microg/mL, 24 h, p<0.05). Subsequent VEGF-induced phosphorylation of eNOS downstream of Akt was completely inhibited in CRP-treated EC. In contrast, CRP-pretreatment did not affect VEGF-induced phosphorylation of ERK1/2. Interestingly, stimulation of EC with CRP for 16-24 h induced marked expression of the phosphatase and tensin homolog (PTEN), which functions as a negative regulator of phosphatidylinositol 3 kinase (PI3K) -->Akt signalling. CONCLUSION: The observed time course for CRP-mediated PTEN upregulation corresponds to the exposure time needed for inhibition of Akt phosphorylation and migration and may therefore constitute a potential mechanism by which CRP inhibits inducible Akt phosphorylation and EC migration.