HDL (High-Density Lipoprotein) Remodeling and Magnetic Resonance Imaging-Assessed Atherosclerotic Plaque Burden: Study in a Preclinical Experimental Model.

OBJECTIVE: HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression. Approach and Results: Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression (P<0.05 versus basal). Plaque characterization showed that HC-HDL administered animals had a 2-fold higher lipid and cholesterol content versus those infused NC-HDL and vehicle (P<0.05). No differences were observed among groups in CD31 levels, nor in infiltrated macrophages or smooth muscle cells. Plaques from HC-HDL administered animals exhibited higher Casp3 (caspase 3) content (P<0.05 versus vehicle and NC-HDL) whereas plaques from NC-HDL infused animals showed lower expression of Casp3, Cox1 (cyclooxygenase 1), inducible nitric oxide synthase, and MMP (metalloproteinase) activity (P<0.05 versus HC-HDL and vehicle). HDLs isolated from animals administered HC-HDL displayed lower antioxidant potential and cholesterol efflux capacity as compared with HDLs isolated from NC-HDL-infused animal and vehicle or donor HDL (P<0.05). There were no differences in HDL-ApoA1 content, ABCA1 (ATP-binding cassette transporter A1) vascular expression, and SRB1 (scavenger receptor B1) and ABCA1 liver expression. CONCLUSIONS: HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions.

Society for Cardiovascular Magnetic Resonance 2020 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients With Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction.

BACKGROUND: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. METHODS: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. RESULTS: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9-21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8-13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6-266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9-22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7-13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8-271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9-29.4), 4.9 (95% CI, 1.3-18.9), and 11.8 (95% CI, 4.3-32.3), respectively. CONCLUSIONS: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.

Complex adult congenital heart disease on cross-sectional imaging: an introductory overview.

Congenital heart disease is the most common group of congenital pathology. Over the past few decades, advances in surgical treatment have resulted in a rising population of adult patients with repaired complex congenital heart disease. Although the quality of life has greatly improved, a significant proportion of morbidities encountered in clinical practice is now seen in adults rather than in children. These patients often have significant haemodynamic pathophysiology necessitating repeat intervention. CT and MRI are excellent imaging modalities, which help elucidate potential complications that may need urgent management. Although imaging should be performed in specialised centres, occasionally patients may present acutely to emergency departments in hospitals with little experience in managing potentially complex patients. The purpose of this article is to provide an introductory overview to the radiologist who may not be familiar with complex congenital heart disease in adult patients. This educational review has three main sections: (1) a brief overview of the post-operative anatomy and surgical management of the most common complex conditions followed by (2) a discussion on CT/MRI protocols and (3) a review of the various complications and their CT/MRI findings.

Cardiac sarcoidosis in an adult person with cystic fibrosis: a case report.

Cardiac sarcoidosis and cystic fibrosis (CF) are both rare conditions and their co-existence has not previously been noted in adults. For the first time we report a case of isolated cardiac sarcoidosis in a woman with CF, and discuss the possible combined aetiological factors. As the life expectancy of people with CF continues to increase, clinicians should be aware of the emergence of concomitant inflammatory conditions typically diagnosed in adulthood, and the diagnostic challenges this may present.

Multimodality Imaging of the Mitral Valve: Morphology, Function, and Disease.

The mitral valve apparatus is one of the key structures of the heart with complex anatomy and function. The prevalence of mitral valve disease is associated with age: elderly people are affected more frequently. There are multiple inherited and acquired conditions; tumors may also involve the mitral valve. Stenosis and regurgitation are the main manifestations of valvular disease. Echocardiography, computed tomography, and cardiovascular magnetic resonance imaging are widely applied techniques for anatomical and functional evaluation of the mitral valve. Each of the modalities has unique applications and limitations, therefore assessment of mitral valve disease requires a multimodality imaging approach. In this pictorial essay, we review normal anatomy and physiology of the mitral valve as well as multimodality imaging manifestations of mitral valve disease.

Limitations of cardiothoracic ratio derived from chest radiographs to predict real heart size: comparison with magnetic resonance imaging.

BACKGROUND: Cardiothoracic ratio (CTR) in chest radiographs is still widely used to estimate cardiac size despite the advent of newer imaging techniques. We hypothesise that a universal CTR cut-off value of 50% is a poor indicator of cardiac enlargement. Our aim was to compare CTR with volumetric and functional parameters derived from cardiac magnetic resonance imaging (MRI). METHODS: 309 patients with a chest radiograph and cardiac MRI acquired within a month were reviewed to assess how CTR correlates with multiple cardiac MRI variables: bi-ventricular EDV (absolute and indexed to body surface area), EF, indexed total heart volume and bi-atrial areas. In addition, we have also determined CTR accuracy by creating multiple ROC curves with the described variables. RESULTS: All cardiac MRI variables correlate weakly but statistically significantly with CTR. This weak correlation is explained by a substantial overlap of cardiac MRI parameters in patients with normal and increased CTR. For all variables, CTR was only mildly to moderately better than a chance to discriminate cardiac enlargement (AUC 0.6-0.7). Large CTR values (> 55%) are specific but not sensitive, while low CTR values (< 45%) are sensitive but not specific. Values in between are not sensitive nor specific. CONCLUSIONS: CTR correlates weakly with true chamber size assessed by gold standard cardiac MRI and has a weak discriminatory power. Thus, clinical decisions based on intermediate CTRs (45-55%) should be avoided. Large CTRs (> 55%) are likely indicative of true heart chamber enlargement. Low CTRs (< 45%) are likely indicative of normal heart size.

Myocardial rupture and left ventricular pseudoaneurysm due to late STEMI presentation during the COVID-19 pandemic lockdown: a classical case report.

BACKGROUND: Left ventricular (LV) pseudoaneurysm is a serious and rare complication of myocardial infarction (MI). It occurs when an injured myocardial wall ruptures and is contained by overlying adherent pericardium or scar tissue, most commonly it develops in patients with late presentation of MI and delayed revascularization. CASE SUMMARY: A 64-year-old man presented to the emergency department with intermittent central chest pain radiating to back and neck and increasing on deep inspiration, which was considered to be of musculoskeletal origin for a week, but worsened despite medications. Electrocardiography showed features of ST-elevation MI; a circumflex artery occlusion was found on coronary angiogram and angioplasty was performed. Cardiovascular magnetic resonance (CMR) revealed features of healed lateral wall rupture with adherent parietal pericardium and the patient was managed conservatively. Two months later the patient returned with severe chest pain; echocardiogram and cardiac computed tomography showed significant interval progression of the pseudoaneurysm. Aneurysmectomy was performed, after which the patient recovered and had none of the previous symptoms since. Follow-up CMR study revealed improvement of LV systolic function. DISCUSSION: A rare case of post-infarction LV pseudoaneurysm was reported. Multimodality imaging helped to detect and to differentiate this complication from the true aneurysm and to follow it up and plan the treatment. Conservative treatment was not effective in this case as the pseudoaneurysm progressed; aneurysmectomy helped to improve LV systolic function.

Multimodality Imaging of Cor Triatriatum Sinister in an Adult.

Supplemental material is available for this article.

A case report of malignant primary pericardial mesothelioma with atypical imaging appearance: multimodality imaging with histopathological correlation.

BACKGROUND: Primary pericardial mesothelioma is a rare primary cardiac malignancy, with three main histopathological types, sarcomatoid histotype being the rarest. The imaging features were atypical due to concomitant extensive calcification, which resulted in aggravated differential diagnosis. CASE SUMMARY: A 45-year-old man presented to our hospital with non-specific clinical symptoms. According to clinical history, a mediastinal tumour had been suspected with a previous unsuccessful attempt of transthoracic computed tomography-guided biopsy at an overseas hospital with limited data of performed imaging procedures. Multimodality imaging at our centre revealed extensively calcified solid masses in the pericardium, invading the left atrium. As the imaging features suggested an atypical primary pericardial malignancy, a diagnostic thoracoscopy was performed. Histopathological analysis of specimen revealed sarcomatoid type of pericardial mesothelioma with areas of necrosis and foci of osteogenic differentiation. Despite planned treatment, 2 weeks after histological diagnosis, the patient passed away due to perforated peptic ulcer-related sepsis. DISCUSSION: The presence of extensive calcification in the lesion resulted in a challenging imaging workup and diagnosis. Initial differential diagnosis included primary or metastatic calcification-prone tumour, secondary calcification due to haemorrhage after previous interventional procedure and other pathologies, such as tuberculous pericarditis, calcified amorphous tumour, among others. Calcification may be part of the histological tumour characteristics; however, proper history taking is crucial as concomitant diseases, previous treatment, and interventional procedures may alter the imaging pattern.

Intravenous Statin Administration During Myocardial Infarction Compared With Oral Post-Infarct Administration.

BACKGROUND: Beyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown. OBJECTIVES: This study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI. METHODS: Hypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed. RESULTS: At day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups. CONCLUSIONS: Intravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.

Gender discrepancy in research activities during radiology residency.

OBJECTIVE: To investigate the presence of gender disparity in academic involvement during radiology residency and to identify and characterize any gender differences in perceived barriers for conducting research. METHODS: An international call for participation in an online survey was promoted via social media and through multiple international and national radiological societies. A 35-question survey invited radiology trainees worldwide to answer questions regarding exposure and barriers to academic radiology during their training. Gender differences in response proportions were analyzed using either Fisher's exact or chi-squared tests. RESULTS: Eight hundred fifty-eight participants (438 men, 420 women) from Europe (432), Asia (241), North and South America (144), Africa (37), and Oceania (4) completed the survey. Fewer women radiology residents were involved in research during residency (44.3%, 186/420 vs 59.4%, 260/438; p ≤ 0.0001) and had fewer published original articles (27.9%, 117/420 vs. 40.2%, 176/438; p = 0.001). Women were more likely to declare gender as a barrier to research (24.3%, 102/420 vs. 6.8%, 30/438; p < 0.0001) and lacked mentorship/support from faculty (65%, 273/420 vs. 55.7%, 244/438; p = 0.0055). Men were more likely to declare a lack of time (60.3%, 264/438 vs. 50.7%, 213/420; p = 0.0049) and lack of personal interest (21%, 92/438 vs. 13.6%, 57/420, p = 0.0041) in conducting research. CONCLUSION: Fewer women were involved in academic activities during radiology residency, resulting in fewer original published studies compared to their men counterparts. This is indicative of an inherent gender imbalance. Lack of mentorship reported by women radiologists was a main barrier to research.

Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement.

OBJECTIVES: This study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort. BACKGROUND: The relationship between LGE and prognosis in DCM is incompletely understood. METHODS: The authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM. RESULTS: Of 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern. CONCLUSIONS: In DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.

Intracellular platelet signalling as a target for drug development.

Platelets are endowed with a repertoire of surface receptors that enable them to adhere, activate and aggregate upon vascular injury. Platelet adhesion is governed by the interaction between vascular collagen and GPIb-IX-V and GPVI-FcRγ complexes. Platelet kinases downstream 14-3-3ζ-bound GPIb and the FcRγ ITAM domain enable the activation of PLC-γ2 whereas the engagement of soluble agonists (predominantly ADP, TXA2 and thrombin) with Gq-protein coupled receptor trigger PLC-ß activation. Once activated, PLC-γ2/ß induces the generation of second messengers IP3 and DAG. IP3 is involved in Ca2+ cytosolic release from the dense tubular system whereas DAG induces PKC activation. CalDAG-GEFI sensors Ca2+ mobilization and, through activation of the small GTPase Rap1, induces cytoskeleton re-arrangements, extrusion of platelet granules and conversion of integrin αIIbß3 into a high-affinity state ("inside-out" signalling). These events are found to be reinforced by PKC, MAPK, and ROS-dependent GPVI pathways. Finally, ligand-interaction with αIIbß3 bridges platelets together and triggers "outside-in" signalling that orchestrates cytoskeletal rearrangements for platelet spreading and clot stabilization through the PI3K/PDK1/Akt/GSK3 axis. Understanding the platelet signalling machinery involved in thrombus formation is necessary to identify potential targets for the development of new antiplatelet agents.

Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy.

AIM: To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM). METHODS AND RESULTS: We used proportional hazard modelling to examine the association between sex, age and all-cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.9 years. Women were more likely to present with heart failure (64.0% vs. 54.5%; P = 0.007) and had more severe symptoms (P < 0.0001) compared to men. Women had smaller left ventricular end-diastolic volume (125 mL/m2 vs. 135 mL/m2 ; P < 0.001), higher left ventricular ejection fraction (40.2% vs. 37.9%; P = 0.019) and were less likely to have mid-wall late gadolinium enhancement (23.0% vs. 38.9%; P < 0.0001). During follow-up, 149 (16.9%) patients died, including 41 (4.7%) who died suddenly. After adjustment, all-cause mortality [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.92; P = 0.018] was lower in women, with similar trends for cardiovascular (HR 0.60, 95% CI 0.35-1.05; P = 0.07), non-sudden (HR 0.63, 95% CI 0.39-1.02; P = 0.06) and sudden death (HR 0.70, 95% CI 0.30-1.63; P = 0.41). All-cause mortality (per 10 years: HR 1.36, 95% CI 1.20-1.55; P < 0.0001) and non-sudden death (per 10 years: HR 1.51, 95% CI 1.26-1.82; P < 0.00001) increased with age. Cumulative incidence curves confirmed favourable outcomes, particularly in women and those <60 years. Increased all-cause mortality in patients >60 years of age was driven by non-sudden death. CONCLUSION: Women with DCM have better survival compared to men, which may partly be due to less severe left ventricular dysfunction and a smaller scar burden. There is increased mortality driven by non-sudden death in patients >60 years of age that is less marked in women. Outcomes with contemporary treatment were favourable, with a low incidence of sudden death.

Challenging Occam's Razor: An Unusual Combination of Sarcoidosis and Amyloidosis. The Value of Cardiac Magnetic Resonance Imaging in Infiltrative Cardiomyopathies.

We describe the case of a 66-year old woman with the extremely rare combination of sarcoidosis and amyloidosis (light chain) and the important role of cardiovascular magnetic resonance imaging to differentiate between these 2 infiltrative diseases. Myocardial characterization with T1 mapping can improve disease detection, especially in overlap cases, and possibly obviate the need for cardiac biopsy.

Multimodality imaging in a late septic infection of aortic graft.

A 70-year-old diabetic female patient presented with fatigue, headaches, hallucinations and shivers following a history of sinusitis and ophthalmitis. She had an aortic surgery performed 7 years ago for a stenotic and regurgitant aortic valve with aneurysm of the ascending aorta. Work-up brain MRI revealed septic-embolic encephalitis. Multimodality cardiovascular imaging showed abnormal anterior wall of the ascending aortic graft with vegetation extending into the lumen. Blood culture was only positive for Aggregatibacter actinomycetemcomitans, an uncommon cause of infective endocarditis. During aortic surgery, the intraluminal vegetation with suppurated perigraft tissue was confirmed.