Julian A. Luetkens

Acute Myocarditis: Multiparametric Cardiac MR Imaging

PURPOSE To evaluate the diagnostic value of cardiac magnetic resonance (MR) imaging at 3 T in patients suspected of having acute myocarditis by using a multiparametric cardiac MR imaging approach including T1 relaxation time as an additional tool for tissue characterization. MATERIALS AND METHODS Ethics commission approval was obtained for this prospective study, and written informed consent was obtained from all subjects. Twenty four patients with acute myocarditis (mean age ± standard deviation, 34.7 years ± 15.1; 75% men) and 42 control subjects (mean age, 38.7 years ± 10.2; 64% men) were included. Cardiac MR imaging approaches included relative T2 short tau inversion-recovery signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late gadolinium enhancement, native T1 relaxation times, and extracellular volume fraction. Receiver operating characteristic analysis was performed to compare diagnostic performance. The reference standard was the clinical evidence for acute myocarditis. RESULTS Native T1 relaxation times were significantly longer in patients with acute myocarditis than in control subjects (1185.3 msec ± 49.3 vs 1089.1 msec ± 44.9, respectively; P < .001). Areas under the curve of native T1 relaxation times (0.94) were higher compared with those of other cardiac MR parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018, .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were equivalent compared with those of the established combined Lake Louise criteria (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%). CONCLUSION Diagnostic performance with native T1 mapping was superior to that with T2 ratio and early gadolinium enhancement ratio, and specificity was higher with native T1 mapping than that with Lake Louise criteria. This study underlines the potential of native T1 relaxation times to complement current cardiac MR approaches in patients suspected of having acute myocarditis.

Incremental value of quantitative CMR including parametric mapping for the diagnosis of acute myocarditis

AIM Cardiac magnetic resonance (CMR) can visualize inflammatory tissue changes in acute myocarditis. Several quantitative image-derived parameters have been described to enhance the diagnostic value of CMR, but no direct comparison of these techniques is available. METHODS AND RESULTS A total of 34 patients with suspected acute myocarditis and 50 control subjects underwent CMR. CMR protocol included quantitative assessment of T1 relaxation times using modified Look-Locker inversion recovery (MOLLI) and shortened MOLLI (ShMOLLI) acquisition schemes, extracellular volume fraction (ECV), T2 relaxation times, and longitudinal strain. Established Lake-Louise criteria (LLC) consisting of T2-weighted signal intensity ratio (T2-ratio), early gadolinium enhancement ratio (EGEr), and late gadolinium enhancement (LGE) were assessed. Receiver operating characteristics analysis was performed to compare diagnostic performance. Areas under the curve of native T1 (MOLLI: 0.95; ShMOLLI: 0.92) and T2 relaxation times (0.92) were higher compared with those of the other CMR parameters (T2-ratio: 0.71, EGEr: 0.71, LGE: 0.87, LLC: 0.90, ECV MOLLI: 0.77, ECV ShMOLLI: 0.80, longitudinal strain: 0.83). Combined with LGE, each native mapping technique outperformed the diagnostic performance of LLC (P < 0.01, respectively). A combination of native parameters (T1, T2, and longitudinal strain) significantly increased the diagnostic performance of CMR compared with LLC without need of contrast media application (0.99 vs. 0.90; P = 0.008). CONCLUSION In patients suspected of having acute myocarditis, diagnostic performance of CMR can be improved by implementation of quantitative CMR parameters. Especially, native mapping techniques have the potential to replace current LLC. CLINICALTRIALS. GOV NUMBER NCT02299856.

Comprehensive Cardiac Magnetic Resonance for Short‐Term Follow‐Up in Acute Myocarditis

Background Cardiac magnetic resonance (CMR) can detect inflammatory myocardial alterations in patients suspected of having acute myocarditis. There is limited information regarding the degree of normalization of CMR parameters during the course of the disease and the time window during which quantitative CMR should be most reasonably implemented for diagnostic work‐up. Methods and Results Twenty‐four patients with suspected acute myocarditis and 45 control subjects underwent CMR. Initial CMR was performed 2.6±1.9 days after admission. Myocarditis patients underwent CMR follow‐up after 2.4±0.6, 5.5±1.3, and 16.2±9.9 weeks. The CMR protocol included assessment of standard Lake Louise criteria, T1 relaxation times, extracellular volume fraction, and T2 relaxation times. Group differences between myocarditis patients and control subjects were highest in the acute stage of the disease (P<0.001 for all parameters). There was a significant and consistent decrease in all inflammatory CMR parameters over the course of the disease (P<0.01 for all parameters). Myocardial T1 and T2 relaxation times—indicative of myocardial edema—were the only single parameters showing significant differences between myocarditis patients and control subjects on 5.5±1.3‐week follow‐up (T1: 986.5±44.4 ms versus 965.1±28.1 ms, P=0.022; T2: 55.5±3.2 ms versus 52.6±2.6 ms; P=0.001). Conclusions In patients with acute myocarditis, CMR markers of myocardial inflammation demonstrated a rapid and continuous decrease over several follow‐up examinations. CMR diagnosis of myocarditis should therefore be attempted at an early stage of the disease. Myocardial T1 and T2 relaxation times were the only parameters of active inflammation/edema that could discriminate between myocarditis patients and control subjects even at a convalescent stage of the disease.

Cardiac Magnetic Resonance Reveals Signs of Subclinical Myocardial Inflammation in Asymptomatic HIV-Infected Patients.

Background—People living with chronic HIV infection are at an increased risk for cardiovascular disease. With this study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients by a comprehensive cardiac magnetic resonance (CMR) approach. Methods and Results—Asymptomatic patients with chronic HIV infection undergoing combination antiretroviral therapy (n=28) and control subjects (n=22) underwent CMR. HIV-infected patients were successfully controlled for the disease with a consistent plasma viremia of <200 copies/mL (mean CD4+-cell count, 475.1±307.9 cells/&mgr;L). CMR protocol allowed for the determination of cardiac function, myocardial inflammation, myocardial fibrosis, aortic stiffness, and pericardial fat volume. When compared with healthy controls, HIV-infected patients showed alterations in left ventricular function as demonstrated by a lower ejection fraction (60.9±7.1% versus 65.2±5.5%; P=0.023) and lower global peak systolic longitudinal and circumferential strain values (longitudinal strain, −17.7±3.4% versus −20.2±3.2%, circumferential strain, −21.2±4.6% versus −24.7±5.1%; P<0.001, respectively). CMR parameters indicating myocardial inflammation were elevated in HIV-infected patients (native T1 relaxation times, 1128.3±53.4 ms versus 1086.5±54.5 ms; P=0.009; relative T2 signal intensity ratio, 1.6±0.3 versus 1.4±0.3; P=0.046; early gadolinium enhancement ratio, 3.1±1.2 versus 2.1±0.6; P=0.003). Myocardial fibrosis, predominantly at the subepicardium of the midventricular and basal inferolateral wall, was prevalent in 82.1% of HIV-infected patients, but only in 27.3% of healthy controls (P<0.001). Conclusions—Comprehensive CMR revealed a high burden of cardiovascular disease in asymptomatic HIV-infected patients. Subclinical myocardial inflammation as detected by CMR may be a potential precursor of the increased cardiovascular morbidity and mortality observed in patients with chronic HIV infection.

The Achilles tendon is mechanosensitive in older adults: adaptations following 14 weeks versus 1.5 years of cyclic strain exercise.

ABSTRACT The aging musculoskeletal system experiences a general decline in structure and function, characterized by a reduced adaptability to environmental stress. We investigated whether the older human Achilles tendon (AT) demonstrates mechanosensitivity (via biomechanical and morphological adaptations) in response to long-term mechanical loading. Thirty-four female adults (60–75 years) were allocated to either a medium-term (14 weeks; N=21) high AT strain cyclic loading exercise intervention or a control group (N=13), with 12 participants continuing with the intervention for 1.5 years. AT biomechanical properties were assessed using ultrasonography and dynamometry. Tendon cross-sectional area (CSA) was investigated by means of magnetic resonance imaging. A 22% exercise-related increment in ankle plantarflexion joint moment, along with increased AT stiffness (598.2±141.2 versus 488.4±136.9 N mm−1 at baseline), Youngs modulus (1.63±0.46 versus 1.37±0.39 GPa at baseline) and about 6% hypertrophy along the entire free AT were identified after 14 weeks of strength training, with no further improvement after 1.5 years of intervention. The aging AT appears to be capable of increasing its stiffness in response to 14 weeks of mechanical loading exercise by changing both its material and dimensional properties. Continuing exercise seems to maintain, but not cause further adaptive changes in tendons, suggesting that the adaptive time–response relationship of aging tendons subjected to mechanical loading is nonlinear. Highlighted Article: The stiffness of the aging Achilles tendon increases after 14 weeks of mechanical loading exercise by changing its material and dimensional properties, whereas continuing exercise causes no further adaptive changes.

Can Contrast-Enhanced Multi-Detector Computed Tomography Replace Transesophageal Echocardiography for the Detection of Thrombogenic Milieu and Thrombi in the Left Atrial Appendage: A Prospective Study with 124 Patients.

PURPOSE To assess the diagnostic value of contrast-enhanced multi-detector computed tomography (MD-CT) for identifying patients with left atrial appendage (LAA) thrombus or circulatory stasis. MATERIALS AND METHODS 124 patients with a history of atrial fibrillation and/or cerebral ischemia (83 men, mean age 58.6 ± 12.4 years) and with a clinical indication for MD-CT of the heart and for transesophageal echocardiography (TEE) were included in the study. LAA thrombus or thrombogenic milieu was visually identified in TEE and MD-CT. In addition, MD-CT was analyzed quantitatively measuring the Hounsfield units (HU) of the left atrium (LA), the LAA and the ascending aorta (AA), and calculating the HU ratios LAA/AA (HU [LAA/AA]) und LAA/LA (HU [LAA/LA]). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated. RESULTS The prevalence of a thrombus or thrombogenic milieu as assessed by TEE was 21.8 %. The HU ratio was lower in patients with thrombus or thrombogenic milieu (HU [LAA/AA]: 0.590 ± 0.248 vs. 0.909 ± 0.141; p < 0.001 und HU [LAA/LA] 0.689 ± 0.366 vs. 1.082 ± 0.228; p < 0.001). For the diagnosis of thrombus or a thrombogenic milieu, visual analysis yielded a sensitivity of 81.5 %, a specificity of 96.9 %, a PPV of 87.5 % and a NPV of 95.2 %. By combining visual and quantitative analysis with one criterion being positive, the specificity decreased to 91.8 %, the sensitivity to 77.8 %, the PPV to 72.4 %, and the NPV to 94.9 %. CONCLUSION Visual analysis of the LAA in the evaluation of thrombus or thrombogenic milieu yields a high NPV of 95.1 % and may especially be useful to rule out LAA thrombi in patients with contraindications for TEE. Additional calculation of HU ratios did not improve the diagnostic performance of MD-CT. KEY POINTS • MD-CT can reliably exclude atrial appendage thrombi/thrombogenic milieu. • MD-CT is an alternative method in patients with contraindications to TEE. • Calculation of relative HU ratios does not improve the diagnostic value of MD-CT.

Left Ventricular Myocardial Fibrosis, Atrophy, and Impaired Contractility in Patients With Pulmonary Arterial Hypertension and a Preserved Left Ventricular Function: A Cardiac Magnetic Resonance Study.

Purpose: Using a cardiac magnetic resonance (CMR) approach we investigated left ventricular (LV) myocardial changes associated with pulmonary arterial hypertension (PAH) by strain analysis and mapping techniques. Materials and Methods: Seventeen patients with PAH (9 men; mean age, 64.2±13.6 y) and 20 controls (10 men, 63.2±10.5 y) were examined using CMR at 1.5 T. Native LV T1-relaxation times (T1) and extracellular volume fraction (ECV) were assessed using a MOLLI sequence, T2-relaxation times (T2) by means of a gradient spin-echo sequence, and LV longitudinal strain (LVS) and right ventricular (RV) longitudinal strain (RVS) by means of CMR feature tracking. The hematocrit and serum levels of pro-Brain Natriuretic Peptide were determined on the day of the CMR examination. Pulmonary arterial pressure and 6-minute walking distance were assessed as part of the clinical evaluation. Results: T1 and ECV were higher (1048.5±46.6 vs. 968.3±22.9 ms and 32.4%±5.7% vs. 28.4%±3.8%; P<0.05) and LVS was lower in patients with PAH (−18.0±5.6 vs. −23.0±2.9; P<0.01) compared with controls. LV mass and interventricular septal thickness were lower in PAH patients (65.7±18.0 vs. 86.7±26.9 g and 7.6±1.9 vs. 10±2.4 mm; P<0.05); there were no differences in LV ejection fraction (61.2%±6.9% vs. 61.9%±6.7%; P=0.86). T1-derived parameters correlated significantly with RVS, LVS, the 6-minute walking distance, RV ejection fraction, pro-Brain Natriuretic Peptide, and baseline mean pulmonary arterial pressure. There were no significant differences in T2. Conclusions: In patients with PAH, changes in T1 and ECV support the hypothesis of LV myocardial fibrosis and atrophy with a consecutively impaired contractility despite a preserved LV function, possibly due to longstanding PAH-associated LV underfilling.

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography. This study evaluated fat‐free muscle area (FFMA) as a marker of sarcopenia using magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training cohort of 71 patients compared computed tomography–measured transversal psoas muscle thickness with FFMA. In 15 patients MRI was performed before and after TIPS, and in 12 patients follistatin serum measurements were carried out. The results on FFMA were confirmed in a validation cohort of 45 patients. FFMA correlated with follistatin and transversal psoas muscle thickness and showed slightly better association with survival than transversal psoas muscle thickness. Gender‐specific cutoff values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute‐on‐chronic liver failure. FFMA was an independent predictor of survival in these patients. Conclusion: This study offers an easy‐to‐apply MRI‐based measurement of fat‐free muscle mass as a marker of sarcopenia in decompensated patients; while TIPS might improve sarcopenia and thereby survival, persistence of sarcopenia after TIPS is associated with a reduced response to TIPS and a higher risk of acute‐on‐chronic liver failure development and mortality. (Hepatology 2018;67:1014–1026)

Quantitative assessment of systolic and diastolic function in patients with LGE negative systemic amyloidosis using CMR

OBJECTIVES In clinical routine myocardial affection in amyloidosis is assessed by qualitative late gadolinium enhancement (LGE). Recent studies suggest that early cardiac involvement in amyloidosis may be overlooked by qualitative LGE assessment. The aim of this study was to assess possible early cardiac involvement in LGE negative AL patients by means of systolic and diastolic strain assessment and quantitative enhancement. METHODS 51 individuals (17 Patients with LGE positive light-chain amyloidosis (AL) (Group A), 17 Patients with LGE negative systemic AL (Group B), and 17 healthy controls (Group C)) were investigated. SSFP-Cine sequences were acquired in short axis slices as well as horizontal long axis views. Standard CMR parameters as well as Feature Tracking (FT) derived systolic and diastolic circumferential and longitudinal strain parameters were calculated. Additionally, contrast enhanced MRI images were analyzed to quantitatively determine the extent of enhancement. RESULTS AL patients with and without LGE both had significantly lower early diastolic strain rate (EDSR) values and peak systolic longitudinal strain (PSLS) values than healthy controls (EDSR: Group A 63.1±17.6; Group B: 74.46±11.8; Group C: 86.82±12.7; F(2.48)=10.7 p<0.001); (PSLS: Group A: -13.44±1.9%; Group B: -20.31±1.2%; Group C: -23.11±1.4%; F(2.48)=167.6; p<0.001). Analysis of quantitative LGE enhancement revealed increased enhancement in qualitative LGE negative AL patients compared to healthy controls (Group A: 19.6±8.9%; Group B: 8.2±3.9%; Group C: 2.4±1.3% F(2.48)=52.2; p<0.001). CONCLUSION CMR strain analysis detects early systolic and diastolic strain impairment in AL patients lacking qualitative LGE enhancement.

Feature-tracking myocardial strain analysis in acute myocarditis: diagnostic value and association with myocardial oedema

ObjectivesTo investigate the diagnostic value of cardiac magnetic resonance (CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected acute myocarditis and its association with myocardial oedema.MethodsForty-eight patients with suspected acute myocarditis and 35 control subjects underwent CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and radial strain (RS) was performed. Additionally, the protocol allowed for the assessment of T1 and T2 relaxation times.ResultsWhen compared with healthy controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS: -19.5 ± 4.4% vs. -23.6 ± 3.1%, CS: -23.0 ± 5.8% vs. -27.4 ± 3.4%, RS: 28.9 ± 8.5% vs. 32.4 ± 7.4%; P < 0.05, respectively). LS (T1: r = 0.462, P < 0.001; T2: r = 0.436, P < 0.001) and CS (T1: r = 0.429, P < 0.001; T2: r = 0.467, P < 0.001) showed the strongest correlations with T1 and T2 relaxations times. Area under the curve of LS (0.79) was higher compared with those of CS (0.75; P = 0.478) and RS (0.62; P = 0.008).ConclusionsFT CMR myocardial strain analysis might serve as a new tool for assessment of myocardial dysfunction in the diagnostic work-up of patients suspected of having acute myocarditis. Especially, LS and CS show a sufficient diagnostic performance and were most closely correlated with CMR parameters of myocardial oedema.Key Points• Myocardial strain measures are considerably reduced in patients with suspected myocarditis.• Myocardial strain measures can sufficiently discriminate between diseased and healthy patients.• Myocardial strain measures show basic associations with the extent of myocardial oedema/inflammation.