Ulf K Radunski

Performance of T1 and T2 Mapping Cardiovascular Magnetic Resonance to Detect Active Myocarditis in Patients With Recent-Onset Heart Failure

Background—This study evaluated the performance of novel quantitative T1 and T2 mapping cardiovascular magnetic resonance (CMR) techniques to identify active myocarditis in patients with recent-onset heart failure. Methods and Results—Thirty-one consecutive patients with recent-onset heart failure, reduced left ventricular function and clinically suspected myocarditis underwent endomyocardial biopsy and CMR at 1.5 Tesla. The CMR protocol included standard Lake-Louise parameters as well as T1 mapping using a modified Look-Locker inversion recovery sequence and T2 mapping using a hybrid gradient and spin-echo sequence. Short-axis maps were generated using an OsiriX plug-in to calculate global myocardial T1, T2, and extracellular volume fraction. Active myocarditis was defined by ongoing inflammation on endomyocardial biopsy. Endomyocardial biopsy revealed active myocarditis in 16 (52%) of 31 patients. Neither clinical characteristics, standard Lake-Louise CMR parameters, global myocardial T1 nor extracellular volume fraction differed significantly between patients with and without active myocarditis. However, median global myocardial T2 was significantly higher in patients with active myocarditis (65 ms [Q1–Q3, 61–70 ms]) than in patients without active myocarditis (59 ms [Q1–Q3, 55–64 ms]; P<0.01). A cutoff value for global myocardial T2 of ≥60 ms provided a sensitivity, specificity, accuracy, negative and positive predictive value of 94% (70%–100%), 60% (32%–84%), 77% (60%–89%), 90% (56%–100%), and 71% (48%–89%) for active myocarditis, respectively. Conclusions—T2 mapping seems to be superior when compared with standard CMR parameters, global myocardial T1, and extracellular volume fraction values for assessing the activity of myocarditis in patients with recent-onset heart failure and reduced left ventricular function.

Tissue characterization by T1 and T2 mapping cardiovascular magnetic resonance imaging to monitor myocardial inflammation in healing myocarditis

Aims Monitoring disease activity in myocarditis is important for tailored therapeutic strategies. This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance (CMR) to monitor the course of myocardial inflammation in healing myocarditis. Methods and Results Forty-eight patients with strictly defined acute myocarditis underwent CMR at 1.5 T in the acute stage, at 3-months (n = 39), and at 12-months follow-up (FU) (n = 21). Normal values were obtained in a control group of 27 healthy subjects. The CMR protocol included standard (‘Lake-Louise’) sequences as well as T1 (modified Look-Locker inversion recovery sequence, MOLLI) and T2 (gradient- and spin-echo sequence, GraSE) mapping. T1, T2, and extracellular volume (ECV) maps were generated using an OsiriX plug-in. Native myocardial T1, T2, and ECV values were increased in the acute stage, but declined with healing of myocarditis. The performances of global native T1 and T2 to differentiate acute from healed myocarditis stages were significantly better compared with all other global CMR parameters with AUCs of 0.85 (95% CI, 0.76–0.94) and 0.83 (95% CI, 0.73–0.93). Furthermore, regional native T1 and T2 in myocarditis lesions provided AUCs of 0.97 (95% CI, 0.93–1.02) and 0.93 (95% CI, 0.85–1.01), which were significantly superior to any other global or regional CMR parameter. Conclusion Healing of myocarditis can be monitored by native myocardial T1 and T2 measurements without the need for contrast media. Both native myocardial T1 and T2 provide an excellent performance for assessing the stage of myocarditis by CMR.

Acute versus Chronic Myocardial Infarction: Diagnostic Accuracy of Quantitative Native T1 and T2 Mapping versus Assessment of Edema on Standard T2-weighted Cardiovascular MR Images for Differentiation

Purpose To analyze the diagnostic accuracy of native T1 and T2 mapping compared with visual and quantitative assessment of edema on T2-weighted cardiac magnetic resonance (MR) images to differentiate between acute and chronic myocardial infarction. Materials and Methods This study had institutional ethics committee approval. Written informed consent was obtained from 67 consecutive patients (57 years ± 12; 78% men) with a first acute myocardial infarction, who were prospectively enrolled between April 2011 and June 2015. Four serial 1.5-T MR imaging examinations were performed at 8 days ± 5, 7 weeks ± 2, 3 months ± 0.5, and 6 months ± 1.4 after infarction and included T2-weighted, native T1/T2 mapping, and late gadolinium enhancement MR imaging. Complete follow-up data were obtained in 42 patients. Regional native T1/T2 relaxation time, T2-weighted ratio, and extracellular volume were serially measured in infarcted and remote myocardium. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of the MR imaging parameters for discriminating between acute and chronic myocardial infarction. Results Native T1 of infarcted myocardium decreased from 1286 msec ± 99 at baseline to 1077 msec ± 50 at 6 months (P < .0001), whereas T2 decreased from 84 msec ± 10 to 58 msec ± 4 (P < .0001). The T2-weighted ratio decreased from 4.1 ± 1.0 to 2.4 ± 0.6 (P < .0001). Of all the MR imaging parameters obtained, native T1 and T2 yielded the best areas under the ROC curve (AUCs) of 0.975 and 0.979, respectively, for differentiating between acute and chronic myocardial infarction. Visual analysis of the presence of edema at standard T2-weighted cardiac MR imaging resulted in an inferior AUC of 0.863 (P < .01). Conclusion Native T1 and T2 of infarcted myocardium are excellent discriminators between acute and chronic myocardial infarction and are superior to all other MR imaging parameters. Online supplemental material is available for this article.

Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure

Treatment of decompensated heart failure often includes administration of levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in heart failure. We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course. Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 ± 31.1 pmol/l at baseline to 215.02 ± 27.96 pmol/l at 6 h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 ± 1.4-fold increase at baseline vs. 6.0 ± 1.1-fold increase with levosimendan). MPO levels also significantly correlated with diastolic blood pressure over the time course. In a multivariate linear model, the main contributor to systolic, diastolic and mean blood pressure was level of PMN elastase. MPO contributed only in heparin-treated patients, suggesting a more significant role for endothelial-bound MPO than for circulating MPO or elastase with respect to blood pressure regulation. We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients. This mechanism may regulate endothelial function and vascular tone in heart failure patients.

Increased extracellular volume in asymptomatic cocaine abusers detected by cardiovascular magnetic resonance imaging

Background Cocaine abuse is associated with an increased risk for coronary artery disease and myocardial infarction. However, there is a paucity of data on myocardial injury in asymptomatic cocaine abusers. T1 mapping cardiovascular magnetic resonance (CMR) has the ability to quantify diffuse alterations in myocardial tissue composition by assessing the extracellular volume fraction (ECV). This study aimed at detecting silent myocardial injury in cocaine abusers using CMR. Methods CMR was performed in eleven cocaine abusers and eleven matched controls without a history of cardiovascular disease. CMR protocol consisted of standard cine-, T2-STIR- and late gadolinium enhancement (LGE) CMR sequences to assess cardiac volumes and function, myocardial edema and focal myocardial fibrosis, respectively. Myocardial extracellular volume fraction (ECV) was assessed using a T1 mapping sequence (MOLLI) before and after administration of 0.075 mmol/kg gadolinium BOPTA: T1 maps were calculated with a dedicated plug-in written for the OsiriX software. Relaxation rates (1/T1 = R1) were calculated for myocardium and blood pool. The difference in R1 between pre- and post contrast media was calculated as ΔR1. Myocardial ECV was then estimated using the formula: ECV = 1-hematocrit * (ΔR1myocardium/ΔR1blood pool).

T1 and T2 mapping CMR to quantify focal myocardial injury in patients with myocarditis

Background Focal myocardial injury is an important diagnostic feature of myocarditis and is typically assessed by cardiovascular magnetic resonance (CMR) on late gadolinium enhancement (LGE) images. T1 mapping, T2 mapping, and extracellular volume (ECV) imaging are novel techniques which potentially improve the diagnostic value of CMR in myocarditis. This study evaluated the potential of T1 and T2 mapping CMR to assess focal myocardial lesions in myocarditis. Methods We included 20 patients with myocarditis who had typical focal myocardial lesions on LGE images as reference method. Native T1, T2, and ECV maps were acquired in addition to a conventional CMR protocol at 1.5 Tesla. Myocardial lesions were quantified on LGE images by a standard threshold technique using a region of interest in normal appearing myocardium as reference tissue. Furthermore, myocardial lesions were quantified using normal values for native myocardial T1, T2, and ECV obtained from a group of 20 matched healthy controls as reference tissue. Injured myocardium was defined by a signal-intensity, native myocardial T1, T2 and ECV ≥ 2 standard deviations above reference values and expressed in percent of LV myocardium. Results Median lesion size was 14% (9-20%) on LGE images. Areas with normal appearing myocardium on LGE images had significantly increased median native myocardial T1 and ECV values compared to myocardium of healthy volunteers (1085ms (1048-1120ms) vs. 1051ms (1021-1064ms); p<0.01 and 32% (30-35%) vs. 26% (24-27%; p<0.0001, respectively). Consequently, median lesion sizes were larger on native T1 maps (48% (32-56%); p<0.01) and ECV maps (58% (50-66%); p<0.01) compared to the median lesion size on LGE images. Median T2 values did not differ significantly between normal appearing myocardium of patients with myocarditis and myocardium of healthy volunteers (56 ms (54-60 ms) vs. 58 ms (53-62 ms); p=0.47). No significant difference in lesion size was found between T2 maps and LGE images (18% (9-38%); p=0.06). Conclusions Native T1 and ECV maps reveal hidden myocardial injury in patients with myocarditis using myocardium of healthy controls as reference tissue. Funding

Myocardial injury and fibrogenesis: extracellular volume expansion is associated with elevated Galectin-3 levels in patients with myocarditis

Background Myocarditis subsumes a variety of entities, including diverse courses from complete healing to dilated cardiomyopathy with severe myocardial fibrosis. T1-mapping cardiovascular magnetic resonance (CMR) has the ability to quantify myocardial extracellular volume (ECV) as a surrogate of acute and chronic myocardial injury. Galectin-3 is an important mediator of fibrogenesis and contributes to adverse left ventricular (LV) remodeling. This study evaluated, if myocardial ECV expansion is linked to Galectin-3 levels in patients with myocarditis. Methods Galectin-3 blood levels were measured in 20 patients with myocarditis using a commercially available chemiluminescent microparticle immunoassay (ARCHITECT Galectin-3, Abbott Germany). T1 quantification was performed at 1.5 Tesla using the modified Look-Locker inversion-recovery (MOLLI) sequence before and 15 minutes after administration of 0.075 mmol/kg gadolinium-BOPTA. Global myocardial ECV was calculated from T1 maps generated by a dedicated plug-in written for the OsiriX software. Results Median Galectin-3 level was 17.4 ng/mL (interquartile range 13.2 to 20.5 ng/mL) and median global myocardial ECV was 29 % (interquartile range 26 to 33 %) in the study population. There was a significant correlation between Galectin-3 levels and global myocardial ECV (r = 0.50; p < 0.05). In contrast, no significant correlation was found between Galectin-3 levels and LV end-diastolic volumes (r = -0.08; p = ns), LV end-systolic volumes (r = 0.06; p = ns), LV stroke volumes (r = -0.33; p = ns); LV ejection fractions (r = -0.11; p = ns), Troponin T levels (r = 0.20; p = ns) or NT-proBNP levels (r = 0.28; p = ns), respectively. Conclusions Myokardial ECV expansion, as a surrogate for myocardial injury, is associated with increased Galectin-3 levels, indicating activated fibrogenesis in patients with myocarditis. Combining Galectin-3 measurements with ECV-imaging could improve risk stratification beyond conventional imaging parameters or biomarkers in these patients.

Active Atrial Function and Atrial Scar Burden After Multiple Catheter Ablations of Persistent Atrial Fibrillation: ATRIAL FUNCTION AFTER MULTIPLE ABLATIONS

Extensive and repeated substrate modification (SM) is frequently performed as an ablation strategy in persistent atrial fibrillation (persAF). The effect of these extended ablation strategies on atrial function has not been investigated sufficiently so far. The purpose was to assess atrial function by cardiac magnetic resonance (CMR) and its association with left atrial (LA) scar burden by electroanatomical voltage‐mapping after multiple persAF ablation procedures.

Prediction of the estimated 5-year risk of sudden cardiac death and syncope or non-sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy using late gadolinium enhancement and extracellular volume CMR

AbstractObjectivesTo evaluate the ability of late gadolinium enhancement (LGE) and mapping cardiac magnetic resonance (CMR) including native T1 and global extracellular volume (ECV) to identify hypertrophic cardiomyopathy (HCM) patients at risk for sudden cardiac death (SCD) and to predict syncope or non-sustained ventricular tachycardia (VT).MethodsA 1.5-T CMR was performed in 73 HCM patients and 16 controls. LGE size was quantified using the 3SD, 5SD and full width at half maximum (FWHM) method. T1 and ECV maps were generated by a 3(3)5 modified Look-Locker inversion recovery sequence. Receiver-operating curve analysis evaluated the best parameter to identify patients with increased SCD risk ≥4% and patients with syncope or non-sustained VT.ResultsGlobal ECV was the best predictor of SCD risk with an area under the curve (AUC) of 0.83. LGE size was significantly inferior to global ECV with an AUC of 0.68, 0.70 and 0.70 (all P < 0.05) for 3SD-, 5SD- and FWHM-LGE, respectively. Combined use of the SCD risk score and global ECV significantly improved the diagnostic accuracy to identify HCM patients with syncope or non-sustained VT.ConclusionsCombined use of the SCD risk score and global ECV has the potential to improve HCM patient selection, benefiting most implantable cardioverter defibrillators.Key Points• Global ECV identified the best HCM patients with increased SCD risk. • Global ECV performed equally well compared to a SCD risk score. • Combined use of the SCD risk score and global ECV improved test accuracy. • Combined use potentially improves selection of HCM patients for ICD implantation.

T1 mapping cardiovascular magnetic resonance imaging to detect myocarditis-Impact of slice orientation on the diagnostic performance.

BACKGROUND T1 mapping is a promising diagnostic tool to improve the diagnostic accuracy of cardiovascular magnetic resonance (CMR) in patients with suspected myocarditis. However, there are currently no data on the potential influence of slice orientation on the diagnostic performance of CMR. Thus, we compared the diagnostic performance of global myocardial T1 and extracellular volume (ECV) values to differentiate patients with myocarditis from healthy individuals between different slice orientations. METHODS This study included 48 patients with clinically defined myocarditis and 13 healthy controls who underwent CMR at 1.5T. A modified Look-Locker inversion-recovery (MOLLI) sequence was used for T1 mapping before and 15min after administration of 0.075mmol/kg Gadolinium-BOPTA. T1 mapping was performed on three short and on three long axes slices, respectively. Native T1, post-contrast T1 and extracellular volume (ECV) -BOPTA maps were calculated using a dedicated plug-in written for the OsiriX software and compared between the mean value of three short-axes slices (3SAX), the central short-axis (1SAX), the mean value of three long-axes slices (3LAX), the four-chamber view (4CH), the three-chamber view (3CH) and the two-chamber view (2CH). RESULTS There were significantly lower native T1 values on 3LAX (1081ms (1037-1131ms)) compared to 3SAX (1107ms (1069-1143ms), p=0.0022) in patients with myocarditis, but not in controls (1026ms (1009-1059ms) vs. 1039ms (1023-1055ms), p=0.2719). The areas under the curve (AUC) to discriminate between myocarditis and healthy controls by native myocardial T1 were 0.85 (p<0.0001) on 3SAX, 0.85 (p<0.0001) on 1SAX, 0.76 (p=0.0002) on 3LAX, 0.70 (p=0.0075) on 4CH, 0.72 (p=0.0020) on 3CH and 0.75 (p=0.0003) on 2CH. The AUCs for ECV-BOPTA were 0.83 (p<0.0001) on 3 SAX, 0.82 (p<0.0001) on 1SAX, 0.77 (p=0.0005) on 3LAX, 0.71 (p=0.0079) on 4CH, 0.69 (p=0.0371) on 3CH and 0.75 (p=0.0006) on 2CH. CONCLUSION Native T1 and ECV-BOPTA on short axes slices provide a better diagnostic performance in myocarditis than long axes slices since long axes slices seem to underestimate native myocardial T1 in myocarditis. T1 mapping in suspected myocarditis can be restricted to a single mid-ventricular short-axis slice without a significant loss in diagnostic performance.