Quantification of myocardial scar of different etiology using dark- and bright-blood late gadolinium enhancement cardiovascular magnetic resonance.

Dark-blood late gadolinium enhancement (LGE) has been shown to improve the visualization and quantification of areas of ischemic scar compared to standard bright-blood LGE. Recently, the performance of various semi-automated quantification methods has been evaluated for the assessment of infarct size using both dark-blood LGE and conventional bright-blood LGE with histopathology as a reference standard. However, the impact of this sequence on different quantification strategies in vivo remains uncertain. In this study, various semi-automated scar quantification methods were evaluated for a range of different ischemic and non-ischemic pathologies encountered in clinical practice. A total of 62 patients referred for clinical cardiovascular magnetic resonance (CMR) were retrospectively included. All patients had a confirmed diagnosis of either ischemic heart disease (IHD; n = 21), dilated/non-ischemic cardiomyopathy (NICM; n = 21), or hypertrophic cardiomyopathy (HCM; n = 20) and underwent CMR on a 1.5 T scanner including both bright- and dark-blood LGE using a standard PSIR sequence. Both methods used identical sequence settings as per clinical protocol, apart from the inversion time parameter, which was set differently. All short-axis LGE images with scar were manually segmented for epicardial and endocardial borders. The extent of LGE was then measured visually by manual signal thresholding, and semi-automatically by signal thresholding using the standard deviation (SD) and the full width at half maximum (FWHM) methods. For all quantification methods in the IHD group, except the 6 SD method, dark-blood LGE detected significantly more enhancement compared to bright-blood LGE (p < 0.05 for all methods). For both bright-blood and dark-blood LGE, the 6 SD method correlated best with manual thresholding (16.9% vs. 17.1% and 20.1% vs. 20.4%, respectively). For the NICM group, no significant differences between LGE methods were found. For bright-blood LGE, the 5 SD method agreed best with manual thresholding (9.3% vs. 11.0%), while for dark-blood LGE the 4 SD method agreed best (12.6% vs. 11.5%). Similarly, for the HCM group no significant differences between LGE methods were found. For bright-blood LGE, the 6 SD method agreed best with manual thresholding (10.9% vs. 12.2%), while for dark-blood LGE the 5 SD method agreed best (13.2% vs. 11.5%). Semi-automated LGE quantification using dark-blood LGE images is feasible in both patients with ischemic and non-ischemic scar patterns. Given the advantage in detecting scar in patients with ischemic heart disease and no disadvantage in patients with non-ischemic scar, dark-blood LGE can be readily and widely adopted into clinical practice without compromising on quantification.

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Non-rigid motion-compensated 3D whole-heart T2 mapping in a hybrid 3T PET-MR system.

PURPOSE: Simultaneous PET-MRI improves inflammatory cardiac disease diagnosis. However, challenges persist in respiratory motion and mis-registration between free-breathing 3D PET and 2D breath-held MR images. We propose a free-breathing non-rigid motion-compensated 3D T2 -mapping sequence enabling whole-heart myocardial tissue characterization in a hybrid 3T PET-MR system and provides non-rigid respiratory motion fields to correct also simultaneously acquired PET data. METHODS: Free-breathing 3D whole-heart T2 -mapping was implemented on a hybrid 3T PET-MRI system. Three datasets were acquired with different T2 -preparation modules (0, 28, 55 ms) using 3-fold undersampled variable-density Cartesian trajectory. Respiratory motion was estimated via virtual 3D image navigators, enabling multi-contrast non-rigid motion-corrected MR reconstruction. T2 -maps were computed using dictionary-matching. Approach was tested in phantom, 8 healthy subjects, 14 MR only and 2 PET-MR patients with suspected cardiac disease and compared with spin echo reference (phantom) and clinical 2D T2 -mapping (in-vivo). RESULTS: Phantom results show a high correlation (R2 = 0.996) between proposed approach and gold standard 2D T2 mapping. In-vivo 3D T2 -mapping average values in healthy subjects (39.0 ± 1.4 ms) and patients (healthy tissue) (39.1 ± 1.4 ms) agree with conventional 2D T2 -mapping (healthy = 38.6 ± 1.2 ms, patients = 40.3 ± 1.7 ms). Bland-Altman analysis reveals bias of 1.8 ms and 95% limits of agreement (LOA) of -2.4-6 ms for healthy subjects, and bias of 1.3 ms and 95% LOA of -1.9 to 4.6 ms for patients. CONCLUSION: Validated efficient 3D whole-heart T2 -mapping at hybrid 3T PET-MRI provides myocardial inflammation characterization and non-rigid respiratory motion fields for simultaneous PET data correction. Comparable T2 values were achieved with both 3D and 2D methods. Improved image quality was observed in the PET images after MR-based motion correction.

SARS-CoV-2 vaccines and myocarditis.

The development of safe and effective vaccines against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a major turning point in the fight against the Coronavirus 2019 (COVID-19) pandemic. However, pharmacovigilance has revealed a small but significant incidence of cardiac inflammation manifesting clinically as myocarditis or pericarditis, particularly in younger vaccine recipients. The incidence is the highest among men under age 40 within a week of receiving the second dose of the mRNA vaccine. In this review, we summarise the evidence for, and guidelines in relation to, SARS-CoV2 vaccine-related myocarditis.

Anatomic, histologic, and mechanical features of the right atrium: implications for leadless atrial pacemaker implantation.

BACKGROUND: Leadless pacemakers (LPs) may mitigate the risk of lead failure and pocket infection related to conventional transvenous pacemakers. Atrial LPs are currently being investigated. However, the optimal and safest implant site is not known. OBJECTIVES: We aimed to evaluate the right atrial (RA) anatomy and the adjacent structures using complementary analytic models [gross anatomy, cardiac magnetic resonance imaging (MRI), and computer simulation], to identify the optimal safest location to implant an atrial LP human. METHODS AND RESULTS: Wall thickness and anatomic relationships of the RA were studied in 45 formalin-preserved human hearts. In vivo RA anatomy was assessed in 100 cardiac MRI scans. Finally, 3D collision modelling was undertaken assessing for mechanical device interaction. Three potential locations for an atrial LP were identified; the right atrial appendage (RAA) base, apex, and RA lateral wall. The RAA base had a wall thickness of 2.7 ± 1.6 mm, with a low incidence of collision in virtual implants. The anteromedial recess of the RAA apex had a wall thickness of only 1.3 ± 0.4 mm and minimal interaction in the collision modelling. The RA lateral wall thickness was 2.6 ± 0.9 mm but is in close proximity to the phrenic nerve and sinoatrial artery. CONCLUSIONS: Based on anatomical review and 3D modelling, the best compromise for an atrial LP implantation may be the RAA base (low incidence of collision, relatively thick myocardial tissue, and without proximity to relevant epicardial structures); the anteromedial recess of the RAA apex and lateral wall are alternate sites. The mid-RAA, RA/superior vena cava junction, and septum appear to be sub-optimal fixation locations.

Hypertensive Heart Disease-The Imaging Perspective.

Hypertensive heart disease (HHD) develops in response to the chronic exposure of the left ventricle and left atrium to elevated systemic blood pressure. Left ventricular structural changes include hypertrophy and interstitial fibrosis that in turn lead to functional changes including diastolic dysfunction and impaired left atrial and LV mechanical function. Ultimately, these changes can lead to heart failure with a preserved (HFpEF) or reduced (HFrEF) ejection fraction. This review will outline the clinical evaluation of a patient with hypertension and/or suspected HHD, with a particular emphasis on the role and recent advances of multimodality imaging in both diagnosis and differential diagnosis.

Low-rank motion correction for accelerated free-breathing first-pass myocardial perfusion imaging.

PURPOSE: Develop a novel approach for accelerated 2D free-breathing myocardial perfusion via low-rank motion-corrected (LRMC) reconstructions. METHODS: Myocardial perfusion imaging requires high spatial and temporal resolution, despite scan time constraints. Here, we incorporate LRMC models into the reconstruction-encoding operator, together with high-dimensionality patch-based regularization, to produce high quality, motion-corrected myocardial perfusion series from free-breathing acquisitions. The proposed framework estimates beat-to-beat nonrigid respiratory (and any other incidental) motion and the dynamic contrast subspace from the actual acquired data, which are then incorporated into the proposed LRMC reconstruction. LRMC was compared with iterative SENSitivity Encoding (SENSE) (itSENSE) and low-rank plus sparse (LpS) reconstruction in 10 patients based on image-quality scoring and ranking by two clinical expert readers. RESULTS: LRMC achieved significantly improved results relative to itSENSE and LpS in terms of image sharpness, temporal coefficient of variation, and expert reader evaluation. Left ventricle image sharpness was approximately 75%, 79%, and 86% for itSENSE, LpS and LRMC, respectively, indicating improved image sharpness for the proposed approach. Corresponding temporal coefficient of variation results were 23%, 11% and 7%, demonstrating improved temporal fidelity of the perfusion signal with the proposed LRMC. Corresponding clinical expert reader scores (1-5, from poor to excellent image quality) were 3.3, 3.9 and 4.9, demonstrating improved image quality with the proposed LRMC, in agreement with the automated metrics. CONCLUSION: LRMC produces motion-corrected myocardial perfusion in free-breathing acquisitions with substantially improved image quality when compared with iterative SENSE and LpS reconstructions.

Single-heartbeat cardiac cine imaging via jointly regularized nonrigid motion-corrected reconstruction.

The aim of the current study was to develop a novel approach for 2D breath-hold cardiac cine imaging from a single heartbeat, by combining cardiac motion-corrected reconstructions and nonrigidly aligned patch-based regularization. Conventional cardiac cine imaging is obtained via motion-resolved reconstructions of data acquired over multiple heartbeats. Here, we achieve single-heartbeat cine imaging by incorporating nonrigid cardiac motion correction into the reconstruction of each cardiac phase, in conjunction with a motion-aligned patch-based regularization. The proposed Motion-Corrected CINE (MC-CINE) incorporates all acquired data into the reconstruction of each (motion-corrected) cardiac phase, resulting in a better posed problem than motion-resolved approaches. MC-CINE was compared with iterative sensitivity encoding (itSENSE) and Extra-Dimensional Golden Angle Radial Sparse Parallel (XD-GRASP) in 14 healthy subjects in terms of image sharpness, reader scoring (range: 1-5) and reader ranking (range: 1-9) of image quality, and single-slice left ventricular assessment. MC-CINE was significantly superior to both itSENSE and XD-GRASP using 20 heartbeats, two heartbeats, and one heartbeat. Iterative SENSE, XD-GRASP, and MC-CINE achieved a sharpness of 74%, 74%, and 82% using 20 heartbeats, and 53%, 66%, and 82% with one heartbeat, respectively. The corresponding results for reader scoring were 4.0, 4.7, and 4.9 with 20 heartbeats, and 1.1, 3.0, and 3.9 with one heartbeat. The corresponding results for reader ranking were 5.3, 7.3, and 8.6 with 20 heartbeats, and 1.0, 3.2, and 5.4 with one heartbeat. MC-CINE using a single heartbeat presented nonsignificant differences in image quality to itSENSE with 20 heartbeats. MC-CINE and XD-GRASP at one heartbeat both presented a nonsignificant negative bias of less than 2% in ejection fraction relative to the reference itSENSE. It was concluded that the proposed MC-CINE significantly improves image quality relative to itSENSE and XD-GRASP, enabling 2D cine from a single heartbeat.

Simultaneous Highly Efficient Contrast-Free Lumen and Vessel Wall MR Imaging for Anatomical Assessment of Aortic Disease.

BACKGROUND: Bright-blood lumen and black-blood vessel wall imaging are required for the comprehensive assessment of aortic disease. These images are usually acquired separately, resulting in long examinations and potential misregistration between images. PURPOSE: To characterize the performance of an accelerated and respiratory motion-compensated three-dimensional (3D) cardiac MRI technique for simultaneous contrast-free aortic lumen and vessel wall imaging with an interleaved T2 and inversion recovery prepared sequence (iT2Prep-BOOST). STUDY TYPE: Prospective. POPULATION: A total of 30 consecutive patients with aortopathy referred for a clinically indicated cardiac MRI examination (9 females, mean age ± standard deviation: 32 ± 12 years). FIELD STRENGTH/SEQUENCE: 1.5-T; bright-blood MR angiography (diaphragmatic navigator-gated T2-prepared 3D balanced steady-state free precession [bSSFP], T2Prep-bSSFP), breath-held black-blood two-dimensional (2D) half acquisition single-shot turbo spin echo (HASTE), and 3D bSSFP iT2Prep-BOOST. ASSESSMENT: iT2Prep-BOOST bright-blood images were compared to T2prep-bSSFP images in terms of aortic vessel dimensions, lumen-to-myocardium contrast ratio (CR), and image quality (diagnostic confidence, vessel sharpness and presence of artifacts, assessed by three cardiologists on a 4-point scale, 1: nondiagnostic to 4: excellent). The iT2Prep-BOOST black-blood images were compared to 2D HASTE images for quantification of wall thickness. A visual comparison between computed tomography (CT) and iT2Prep-BOOST was performed in a patient with chronic aortic dissection. STATISTICAL TESTS: Paired t-tests, Wilcoxon signed-rank tests, intraclass correlation coefficient (ICC), Bland-Altman analysis. A P value < 0.05 was considered statistically significant. RESULTS: Bright-blood iT2Prep-BOOST resulted in significantly improved image quality (mean ± standard deviation 3.8 ± 0.5 vs. 3.3 ± 0.8) and CR (2.9 ± 0.8 vs. 1.8 ± 0.5) compared with T2Prep-bSSFP, with a shorter scan time (7.8 ± 1.7 minutes vs. 12.9 ± 3.4 minutes) while providing a complementary 3D black-blood image. Aortic lumen diameter and vessel wall thickness measurements in bright-blood and black-blood images were in good agreement with T2Prep-bSSFP and HASTE images (<0.02 cm and <0.005 cm bias, respectively) and good intrareader (ICC > 0.96) and interreader (ICC > 0.94) agreement was observed for all measurements. DATA CONCLUSION: iT2Prep-BOOST might enable time-efficient simultaneous bright- and black-blood aortic imaging, with improved image quality compared to T2Prep-bSSFP and HASTE imaging, and comparable measurements for aortic wall and lumen dimensions. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Evaluation of the impact of the addition of a heart failure prescribing pharmacist to consultant-led heart failure ward round at a tertiary hospital.

OBJECTIVE: Pharmacists attending general medical post-admission ward rounds is established good practice. However, there is a lack of evidence on the impact of specialist heart failure (HF) prescribing pharmacists on consultant HF ward rounds. The aim of this study was to evaluate the impact on prescribing when a specialist HF prescribing pharmacist attended inpatient HF ward rounds. METHODS: A prospective service evaluation completed at a tertiary hospital between September and December 2020. The same HF prescribing pharmacist attended the HF consultant-led ward round once a week on 15 occasions. For each medicine change, the pharmacist documented: who suggested the intervention, the medicine, prescribing action, reason for review and the primary reason for change. Medicines were categorised into four groups (heart failure, cardiovascular, anticoagulation and other) for analysis. RESULTS: A total of 158 patients were reviewed and 226 individual changes suggested; 48% of these were consultant led (n=108) and 52% (n=118) due to pharmacist recommendations. All medicines interventions were prescribed on the round by the pharmacist. For consultants, the primary reason for medicine change was to ensure efficacy of HF medicines, 80% (n=73), followed by safety (HF medicines), 20% (n=18). For the pharmacist, the primary reason was safety across all the medicine groups, 36% (n=42), followed by efficacy relating to missing drug history items, 24% (n=28). CONCLUSIONS: HF consultants focused on ensuring patients have the most effective combination of HF medications. The addition of a specialist HF prescribing pharmacist ensured a wider range of medicines were reviewed for safety and optimisation, helping to deliver a holistic review of all medications.

The complex pathophysiology of cardiac cachexia: A review of current pathophysiology and implications for clinical practice.

Cardiac cachexia is a muscle wasting process that often develops in those with chronic heart failure resulting in weight loss, low levels of physical activity, reduced quality of life, and is associated with a poor prognosis. The pathology of cardiac cachexia is complex with new evidence emerging that implicates several body systems. This review describes the pathophysiology associated with cardiac cachexia and addresses: 1) hormonal changes- neurohormonal abnormalities and metabolic hormone imbalance; 2) mechanisms of muscle wasting in cardiac cachexia, and the integral mechanisms between changed hormones due to cardiac cachexia and muscle wasting processes, and 3) associated abnormalities of gastrointestinal system that contribute to cardiac cachexia. These pleiotropic mechanisms demonstrate the intricate interplay between the affected systems and account for why cardiac cachexia is difficult to manage clinically. This review summarises current pathophysiology of cardiac cachexia and highlights symptoms of cardiac cachexia, implications for clinical practice and research gaps.

Rationale and Design of Rivaroxaban Estimation With Warfarin in Atrial Fibrillation Patients With Coronary Stent Implantation (REWRAPS).

Background: Recent major randomized trials revealed the superiority of non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) from 6 months to 2 years after percutaneous coronary intervention (PCI). However, whether NOAC monotherapy superiority over warfarin continues in real-world patients with a history of atrial fibrillation (AF), coronary stenting, and underlying chronic kidney disease (CKD) >1 year after PCI (e.g., at 5 years) has not been established. Methods and Results: In the Rivaroxaban Estimation with Warfarin in Atrial Fibrillation Patients with Coronary Stent Implantation (REWRAPS) study (NCT02024230), a multicenter, prospective, non-randomized, open-label, physician-initiated efficacy and safety study in Japan, 493 patients received either rivaroxaban or warfarin. The primary efficacy endpoint was major adverse cardiac and cerebrovascular events (MACCE), consisting of cardiac and stroke death, non-fatal myocardial infarction, non-fatal stroke, systemic embolism, and coronary revascularization. The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium 3 and 5). The primary composite endpoint was net adverse clinical events (NACE), defined as a combination of all-cause death and major bleeding. Conclusions: Completion of REWRAPS will provide, for the first time, evidence as to whether rivaroxaban is superior or non-inferior to warfarin with regard to the primary efficacy (MACCE), safety (major bleeding), or combined (all-cause death, major bleeding) endpoints in real-world patients with AF, coronary stenting, and underlying CKD an average of 5 years after PCI.

Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT).

OBJECTIVE: Many patients presenting with suspected acute coronary syndrome (ACS) have high-sensitivity cardiac troponin (hs-cTn) concentrations between rule-in and rule-out thresholds and hence need serial testing, which is time consuming. The Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT) assessed the utility of coronary CT angiography (CCTA) in patients with suspected ACS, non-ischaemic ECG and intermediate initial hs-cTn concentration. METHODS: Patients were randomised to CCTA-guided management versus standard of care (SOC). The primary outcome was hospital length of stay (LOS). Secondary outcomes included cost of in-hospital stay and major adverse cardiac events (MACE) at 12 months of follow-up. Data are mean (SD); for LOS harmonic means, IQRs are shown. RESULTS: 250 (aged 55 (14) years, 25% women) patients were randomised. Harmonic mean (IQR) LOS was 7.53 (6.0-9.6) hours in the CCTA arm and 8.14 (6.3-9.8) hours in the SOC arm (p=0.13). Inpatient cost was £1285 (£2216) and £1108 (£3573), respectively, p=0.68. LOS was shorter in the CCTA group in patients with <25% stenosis, compared with SOC; 6.6 (5.6-7.8) hours vs 7.5 (6.1-9.4) hours, respectively; p=0.021. More referrals for cardiology outpatient clinic review and cardiac CT-related outpatient referrals occurred in the SOC arm (p=0.01). 12-month MACE rates were similar between the two arms (7 (5.6%) in the CCTA arm and 8 (6.5%) in the SOC arm-log-rank p=0.78). CONCLUSIONS: CCTA did not lead to reduced hospital LOS or cost, largely because these outcomes were influenced by the detection of ≥25% grade stenosis in a proportion of patients. TRIAL REGISTRATION NUMBER: NCT03583320.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.