Multiparametric Cardiac Magnetic Resonance Imaging Can Detect Acute Cardiac Allograft Rejection After Heart Transplantation.

OBJECTIVES: The purpose of this study was to evaluate the sensitivity of multiparametric cardiac magnetic resonance imaging (CMR) for the detection of acute cardiac allograft rejection (ACAR). BACKGROUND: ACAR is currently diagnosed by endomyocardial biopsy, but CMR may be a noninvasive alternative because of its capacity for regional myocardial structure and function characterization. METHODS: Fifty-eight transplant recipients (mean age 47.0 ± 14.7 years) and 14 control subjects (mean age 47.7 ± 16.7 years) were prospectively recruited from August 2014 to May 2017 and underwent 97 CMR studies (83 transplant recipients, 14 control subjects) for assessment of global left ventricular function and myocardial T2, T1, and extracellular volume fraction (ECV). CMR studies were divided into 4 groups on the basis of biopsy grade: control subjects (n = 14), patients with no ACAR (no history of ACAR; n = 36), patients with past ACAR (history of ACAR; n = 24), and ACAR+ patients (active grade ≥1R ACAR; n = 23). RESULTS: Myocardial T2 was significantly higher in patients with past ACAR compared with those with no ACAR (51.0 ± 3.8 ms vs. 49.2 ± 4.0 ms; p = 0.02) and in patients with no ACAR compared with control subjects (49.2 ± 4.0 ms vs. 45.2 ± 2.3 ms; p < 0.01). ACAR+ patients demonstrated increased T2 compared with the no ACAR group (52.4 ± 4.7 ms vs. 49.2 ± 4.0 ms, p < 0.01) but not compared with the past ACAR group. In contrast, ECV was significantly elevated in ACAR+ patients compared with transplant recipients without ACAR regardless of history of ACAR (no ACAR: 31.5 ± 3.9% vs. 26.8 ± 3.3% [p < 0.01]; past ACAR: 31.5 ± 3.9% vs. 26.8 ± 4.0% [p < 0.01]). Receiver operating characteristic curve analysis revealed that a combined model of age at CMR, global T2, and global ECV was predictive of ACAR (area under the curve = 0.84). CONCLUSIONS: The combination of CMR-derived myocardial T2 and ECV has potential as a noninvasive tissue biomarker for ACAR. Larger studies during acute ACAR are needed for continued development of multiparametric CMR for transplant recipient surveillance.

Cardiac Structure-Function MRI in Patients After Heart Transplantation.

BACKGROUND: Following heart transplantation (Tx), recipients are closely monitored using endomyocardial biopsy, which is limited by cost and invasiveness, and echocardiography, which is limited regarding detailed structural and functional evaluation. PURPOSE: To test the feasibility of comprehensive structure-function cardiac MRI as a noninvasive modality to assess changes in myocardial structure and function. STUDY TYPE: Prospective. SUBJECTS: MR was performed in 61 heart transplant recipients (age 47.9 ± 16.3 years, 39% female) and 14 age-matched healthy controls (age 47.7 ± 16.7 years, 36% female). FIELD STRENGTH/SEQUENCE: 1.5T; 2D CINE steady state free precession (SSF)P imaging, T2 -mapping, pre- and postgadolinium contrast T1 -mapping, and tissue-phase mapping (TPM). ASSESSMENT: Quantification of myocardial T2 (as a measure of edema), pre- and post-Gd T1 (allowing calculation of extracellular volume (ECV) to estimate interstitial expansion), and TPM-based assessment of peak regional left ventricular (LV) velocities, dyssynchrony, and twist. STATISTICAL TESTS: Comparisons between transplant recipients and controls were performed using independent samples t-tests. Relationships between structural (T2 , T1 , ECV) and functional measures (myocardial velocities, dyssynchrony, twist) were assessed using Pearson correlation analysis. RESULTS: T2 and T1 were significantly elevated in transplant recipients compared to controls (global T2 : 50.5 ± 3.4 msec vs. 45.2 ± 2.3 msec, P < 0.01; global T1 : 1037.8 ± 48.0 msec vs. 993.8 ± 34.1 msec, P < 0.01). Systolic longitudinal function was impaired in transplant recipients compared to controls (reduced peak systolic longitudinal velocities, 2.9 ± 1.1 cm/s vs. 5.1 ± 1.2 cm/s, P < 0.01; elevated systolic longitudinal dyssynchrony, 60.2 ± 30.2 msec vs. 32.1 ± 25.1 msec, P < 0.01). Correlation analysis revealed a significant positive relationship between T2 and ECV (r = 0.45,P < 0.01). In addition, peak systolic longitudinal velocities demonstrated a significant inverse relationship with T2 (global r = -0.29, P = 0.02), and systolic radial dyssynchrony was positively associated with peak T2 and peak T1 (r = 0.26,P = 0.04; r = 0.27,P = 0.03). DATA CONCLUSION: MR techniques are sensitive to structural and functional differences in transplant recipients compared to controls. Structural (T2 , T1 ) and functional (peak myocardial velocities, dyssynchrony) measures were significantly associated, suggesting a structure-function relationship of cardiac abnormalities following heart transplant. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:678-687.

Donor and Recipient Characteristics in Heart Transplantation Are Associated with Altered Myocardial Tissue Structure and Cardiac Function.

PURPOSE: To use structure-function cardiac MRI in the evaluation of relationships between donor and heart transplantation (HTx) recipient characteristics and changes in cardiac tissue structure and function. HTx candidates and donor hearts are evaluated for donor-recipient matches to improve survival, but the impact of donor and recipient characteristics on changes in myocardial tissue and function in the transplanted heart is not fully understood. MATERIALS AND METHODS: Cardiac MRI at 1.5 T was performed from August 2014 to June 2017 in 58 HTx recipients (mean age, 51.1 years ± 12.6 [standard deviation], 26 female patients) and included T2 mapping (to evaluate edematous and/or inflammatory changes), precontrast and postcontrast T1 mapping (allowing the calculation of extracellular volume fraction [ECV] to estimate interstitial expansion), and tissue phase mapping (allowing the calculation of myocardial velocities and twist). Donor and recipient demographics (age, sex, height, weight, and body mass index [BMI]) and comorbidities (hypertension, diabetes, and smoking history) were evaluated for relationships with cardiac MRI measures. RESULTS: Sex-influenced cardiac MRI measures of myocardial tissue and function are as follows: Female HTx recipients demonstrated increased precontrast T1 (P = .002) and reduced systolic peak long-axis velocities (P = .015). Increased age of the donor heart was associated with elevated T2 (r = 0.32; P < .05) and ECV (r = 0.47; P < .01), indicating increased edema and interstitial expansion, as well as impaired diastolic peak long-axis velocities (r = 0.41; P < .01). Recipient-donor differences in age, weight, and BMI were significantly associated with elevated ECV (r = 0.36-0.48; P < .05). Hypertension in donors resulted in increased ECV (31.0% ± 4.2 vs 26.0% ± 3.3; P = .001). CONCLUSION: Donor and HTx recipient characteristics were significantly associated with cardiac MRI-derived measures of myocardial tissue structure and function.© RSNA, 2019.

Validation of highly accelerated real-time cardiac cine MRI with radial k-space sampling and compressed sensing in patients at 1.5T and 3T.

PURPOSE: To validate an optimal 12-fold accelerated real-time cine MRI pulse sequence with radial k-space sampling and compressed sensing (CS) in patients at 1.5T and 3T. METHODS: We used two strategies to reduce image artifacts arising from gradient delays and eddy currents in radial k-space sampling with balanced steady-state free precession readout. We validated this pulse sequence against a standard breath-hold cine sequence in two patient cohorts: a myocardial infarction (n = 16) group at 1.5T and chronic kidney disease group (n = 18) at 3T. Two readers independently performed visual analysis of 68 cine sets in four categories (myocardial definition, temporal fidelity, artifact, noise) on a 5-point Likert scale (1 = nondiagnostic, 2 = poor, 3 = adequate or moderate, 4 = good, 5 = excellent). Another reader calculated left ventricular (LV) functional parameters, including ejection fraction. RESULTS: Compared with standard cine, real-time cine produced nonsignificantly different visually assessed scores, except for the following categories: 1) temporal fidelity scores were significantly lower (P = 0.013) for real-time cine at both field strengths, 2) artifacts scores were significantly higher (P = 0.013) for real-time cine at both field strengths, and 3) noise scores were significantly (P = 0.013) higher for real-time cine at 1.5T. Standard and real-time cine pulse sequences produced LV functional parameters that were in good agreement (e.g., absolute mean difference in ejection fraction <4%). CONCLUSION: This study demonstrates that an optimal 12-fold, accelerated, real-time cine MRI pulse sequence using radial k-space sampling and CS produces good to excellent visual scores and relatively accurate LV functional parameters in patients at 1.5T and 3T. Magn Reson Med 79:2745-2751, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

4D flow MRI, cardiac function, and T1 -mapping: Association of valve-mediated changes in aortic hemodynamics with left ventricular remodeling.

BACKGROUND: Patients with bicuspid aortic valve (BAV) show altered hemodynamics in the ascending aorta that can be assessed by 4D flow MRI. PURPOSE: Comprehensive cardiac MRI was applied to test the hypothesis that BAV-mediated changes in aortic hemodynamics (wall shear stress [WSS] and velocity) are associated with parameters of left ventricular (LV) remodeling. STUDY TYPE: Retrospective data analysis. POPULATION: Forty-nine BAV patients (mean age = 50.2 ± 13.5, 62% male). FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession (bSSFP)-CINE, pre- and postcontrast T1 mapping with modified Look-Locker inversion recovery (MOLLI), time-resolved 3D phase-contrast (PC) MRI with three-directional velocity encoding (4D flow MRI) at 1.5 and 3T. ASSESSMENT: Quantification of LV volumetric data and myocardial mass, extracellular volume fraction (ECV), aortic valve stenosis (AS), and regurgitation (AR). 3D aortic segmentation, quantification of peak systolic velocities, and 3D WSS in the ascending aorta (AAo), arch, and descending aorta (DAo). STATISTICAL TESTS: Two-sided nonpaired t-test to compare subgroups. Pearson correlation coefficient for correlations between aortic hemodynamics and LV parameters. RESULTS: Of the 49 BAV patients, 35 had aortic valve dysfunction (AS [n = 7], AR [n = 16], both AS and AR [n = 12]). Mean systolic WSS in the AAo, peak systolic velocities in the AAo and arch, and LV mass were significantly higher (P < 0.001) in the AS/AR group compared to the patients without AS/AR. In the complete group, we observed significant relationships between increased LV mass and elevated peak systolic velocity (r = 0.57, r = 0.58; P < 0.001) and WSS in the AAo and arch, respectively (r = 0.54, r = 0.46; P < 0.001). We detected an association between ECV and WSS in the AAo (r = 0.38, P = 0.02). These relations did not hold true for patients without AV dysfunction. DATA CONCLUSION: AS and AR in BAV patients have a major impact on elevated aortic peak velocities and WSS that were associated with parameters of LV remodeling. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

Safety of Magnetic Resonance Imaging in Patients with Cardiac Devices.

BACKGROUND: Patients who have pacemakers or defibrillators are often denied the opportunity to undergo magnetic resonance imaging (MRI) because of safety concerns, unless the devices meet certain criteria specified by the Food and Drug Administration (termed "MRI-conditional" devices). METHODS: We performed a prospective, nonrandomized study to assess the safety of MRI at a magnetic field strength of 1.5 Tesla in 1509 patients who had a pacemaker (58%) or an implantable cardioverter-defibrillator (42%) that was not considered to be MRI-conditional (termed a "legacy" device). Overall, the patients underwent 2103 thoracic and nonthoracic MRI examinations that were deemed to be clinically necessary. The pacing mode was changed to asynchronous mode for pacing-dependent patients and to demand mode for other patients. Tachyarrhythmia functions were disabled. Outcome assessments included adverse events and changes in the variables that indicate lead and generator function and interaction with surrounding tissue (device parameters). RESULTS: No long-term clinically significant adverse events were reported. In nine MRI examinations (0.4%; 95% confidence interval, 0.2 to 0.7), the patient's device reset to a backup mode. The reset was transient in eight of the nine examinations. In one case, a pacemaker with less than 1 month left of battery life reset to ventricular inhibited pacing and could not be reprogrammed; the device was subsequently replaced. The most common notable change in device parameters (>50% change from baseline) immediately after MRI was a decrease in P-wave amplitude, which occurred in 1% of the patients. At long-term follow-up (results of which were available for 63% of the patients), the most common notable changes from baseline were decreases in P-wave amplitude (in 4% of the patients), increases in atrial capture threshold (4%), increases in right ventricular capture threshold (4%), and increases in left ventricular capture threshold (3%). The observed changes in lead parameters were not clinically significant and did not require device revision or reprogramming. CONCLUSIONS: We evaluated the safety of MRI, performed with the use of a prespecified safety protocol, in 1509 patients who had a legacy pacemaker or a legacy implantable cardioverter-defibrillator system. No long-term clinically significant adverse events were reported. (Funded by Johns Hopkins University and the National Institutes of Health; ClinicalTrials.gov number, NCT01130896 .).

Accelerated dual-venc 4D flow MRI for neurovascular applications.

PURPOSE: To improve velocity-to-noise ratio (VNR) and dynamic velocity range of 4D flow magnetic resonance imaging (MRI) by using dual-velocity encoding (dual-venc) with k-t generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. MATERIALS AND METHODS: A dual-venc 4D flow MRI sequence with k-t GRAPPA acceleration was developed using a shared reference scan followed by three-directional low- and high-venc scans (repetition time / echo time / flip angle = 6.1 msec / 3.4 msec / 15°, temporal/spatial resolution = 43.0 msec/1.2 × 1.2 × 1.2 mm3 ). The high-venc data were used to correct for aliasing in the low-venc data, resulting in a single dataset with the favorable VNR of the low-venc but without velocity aliasing. The sequence was validated with a 3T MRI scanner in phantom experiments and applied in 16 volunteers to investigate its feasibility for assessing intracranial hemodynamics (net flow and peak velocity) at the major intracranial vessels. In addition, image quality and image noise were assessed in the in vivo acquisitions. RESULTS: All 4D flow MRI scans were acquired successfully with an acquisition time of 20 ± 4 minutes. The shared reference scan reduced the total acquisition time by 12.5% compared to two separate scans. Phantom experiments showed 51.4% reduced noise for dual-venc compared to high-venc and an excellent agreement of velocities (ρ = 0.8, P < 0.001). The volunteer data showed decreased noise in dual-venc data (54.6% lower) compared to high-venc, and improved image quality, as graded by two observers: fewer artifacts (P < 0.0001), improved vessel conspicuity (P < 0.0001), and reduced noise (P < 0.0001). CONCLUSION: Dual-venc 4D flow MRI exhibits the superior VNR of the low-venc acquisition and reliably incorporates low- and high-velocity fields simultaneously. In vitro and in vivo data demonstrate improved flow visualization, image quality, and image noise. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:102-114.

The Safety of Cardiac and Thoracic Magnetic Resonance Imaging in Patients with Cardiac Implantable Electronic Devices.

RATIONALE AND OBJECTIVES: Studies reporting the safety of magnetic resonance imaging (MRI) in patients with a cardiac implantable electronic device (CIED) have mostly excluded examinations with the device in the magnet isocenter. The purpose of this study was to describe the safety of cardiac and thoracic spine MRI in patients with a CIED. MATERIALS AND METHODS: The medical records of patients with a CIED who underwent a cardiac or thoracic spine MRI between January 2011 and December 2014 were reviewed. Devices were interrogated before and after imaging with reprogramming to asynchronous pacing in pacemaker-dependent patients. The clinical interpretability of the MRI and peak and average specific absorption rates (SARs, W/kg) achieved were determined. RESULTS: Fifty-eight patients underwent 51 cardiac and 11 thoracic spine MRI exams. Twenty-nine patients had a pacemaker and 29 had an implantable cardioverter defibrillator. Seventeen percent (n = 10) were pacemaker dependent. Fifty-one patients (89%) had non-MRI-conditional devices. There were no clinically significant changes in atrial and ventricular sensing, impedance, and threshold measurements. There were no episodes of device mode changes, arrhythmias, therapies delivered, electrical reset, or battery depletion. One study was prematurely discontinued due to a patient complaint of chest pain of which the etiology was not determined. Across all examinations, the average peak SAR was 2.0 ± 0.85 W/kg with an average SAR of 0.35 ± 0.37 W/kg. Artifact significantly limiting the clinical interpretation of the study was present in 33% of cardiac MRI studies. CONCLUSIONS: When a comprehensive CIED magnetic resonance safety protocol is followed, the risk of performing 1.5-T magnetic resonance studies with the device in the magnet isocenter, including in patients who are pacemaker dependent, is low.

Simvastatin therapy reduces prooxidant-antioxidant balance: results of a placebo-controlled cross-over trial.

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.

Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial.

OBJECTIVE: This study aimed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins (HSPs) in dyslipidemic patients. DESIGN AND METHODS: Participants (n=102) were treated with simvastatin (40mg/day), or placebo in a randomized, double-blind, placebo-controlled, cross-over trial. Anti-HSP60, 65, 70, and hs-CRP levels were measured before and after each treatment period. Seventy-seven subjects completed the study. RESULTS: Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p<0.001). There have been previous reports of reductions in serum CRP with statin treatment, and although median CRP levels were 9% lower on simvastatin treatment, this did not achieve statistical significance. CONCLUSION: While it is unclear whether HSP antibodies are directly involved in atherogenesis, our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease.