Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Cardiac magnetic resonance imaging before and after therapeutic interventions for systemic sclerosis-associated myocarditis.

OBJECTIVES: Cardiac magnetic resonance imaging (CMRI) is increasingly used to evaluate cardiac involvement in SSc. We assessed changes, including inflammatory and/or fibrotic myocardial lesions detected by CMRI, following therapeutic interventions for SSc-associated symptomatic myocarditis. METHODS: In this retrospective study, myocarditis was diagnosed by CMRI (2018 revised Lake Louise criteria) in 14 diffuse and 4 limited SSc patients [16/18 women, age 56 years (s.d. 11), disease duration 8 years (s.d. 11), 17/18 with lung involvement] with cardiac symptoms and abnormal findings on echocardiography (4/18) and/or in 24-hour Holter monitoring (12/14). CMRI was repeated after 8 months (s.d. 3) following administration of cyclophosphamide (n = 11, combined with corticosteroids in 3 and rituximab in 1), mycophenolate (n = 1), tocilizumab (n = 1), methotrexate/corticosteroids (n = 2), corticosteroids (n = 1) or autologous stem cell transplantation (n = 2). RESULTS: Functional cardiac improvement was evident by increases in left [by 5.8% (s.d. 7.8), P = 0.006] and right ventricular ejection fraction [by 4.5% (s.d. 11.4), P = 0.085] in the second CMRI compared with the first. Notably, late gadolinium enhancement, currently considered to denote replacement fibrosis, decreased by 3.1% (s.d. 3.8; P = 0.003), resolving in six patients. Markers of myocardial oedema, namely T2 ratio and T2 mapping, decreased by 0.27 (s.d. 0.40; P = 0.013) and 6.0 (s.d. 7; P = 0.025), respectively. Conversely, both T1 mapping, considered to reflect acute oedema and diffuse fibrosis, and extracellular volume fraction, reflecting diffuse fibrosis, remained unchanged. CONCLUSIONS: CMRI may distinguish between reversible inflammatory/fibrotic and irreversible fibrotic lesions in SSc patients with active myocarditis, confirming the unique nature of primary cardiac involvement in SSc. Whether, and how, CMRI should be used to monitor treatment effects in SSc-associated myocarditis warrants further study.

Heart Failure and Cardiorenal Syndrome: A Narrative Review on Pathophysiology, Diagnostic and Therapeutic Regimens-From a Cardiologist's View.

In cardiorenal syndrome (CRS), heart failure and renal failure are pathophysiologically closely intertwined by the reciprocal relationship between cardiac and renal injury. Type 1 CRS is most common and associated with acute heart failure. A preexistent chronic kidney disease (CKD) is common and contributes to acute kidney injury (AKI) in CRS type 1 patients (acute cardiorenal syndrome). The remaining CRS types are found in patients with chronic heart failure (type 2), acute and chronic kidney diseases (types 3 and 4), and systemic diseases that affect both the heart and the kidney (type 5). Establishing the diagnosis of CRS requires various tools based on the type of CRS, including non-invasive imaging modalities such as TTE, CT, and MRI, adjuvant volume measurement techniques, invasive hemodynamic monitoring, and biomarkers. Albuminuria and Cystatin C (CysC) are biomarkers of glomerular filtration and integrity in CRS and have a prognostic impact. Comprehensive "all-in-one" magnetic resonance imaging (MRI) approaches, including cardiac magnetic resonance imaging (CMR) combined with functional MRI of the kidneys and with brain MRI are proposed for CRS. Hospitalizations due to CRS and mortality are high. Timely diagnosis and initiation of effective adequate therapy, as well as multidisciplinary care, are pertinent for the improvement of quality of life and survival. In addition to the standard pharmacological heart failure medication, including SGLT2 inhibitors (SGLT2i), renal aspects must be strongly considered in the context of CRS, including control of the volume overload (diuretics) with special caution on diuretic resistance. Devices involved in the improvement of myocardial function (e.g., cardiac resynchronization treatment in left bundle branch block, mechanical circulatory support in advanced heart failure) have also shown beneficial effects on renal function.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases.

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Microvasculopathy-Related Hemorrhagic Tissue Deposition of Iron May Contribute to Fibrosis in Systemic Sclerosis: Hypothesis-Generating Insights from the Literature and Preliminary Findings.

Microvascular wall abnormalities demonstrated by nailfold capillaroscopy in systemic sclerosis (SSc) may result in microhemorrhagic deposition of erythrocyte-derived iron. Such abnormalities precede fibrosis, which is orchestrated by myofibroblasts. Iron induces endothelial-to-mesenchymal transition in vitro, which is reversed by reactive oxygen species (ROS) scavengers. The conversion of quiescent fibroblasts into profibrotic myofibroblasts has also been associated with ROS-mediated activation of TGF-ß1. Given that iron overload predisposes to ROS formation, we hypothesized that the uptake of erythrocyte-derived iron by resident cells promotes fibrosis. Firstly, we show that iron induces oxidative stress in skin-derived and synovial fibroblasts in vitro, as well as in blood mononuclear cells ex vivo. The biological relevance of increased oxidative stress was confirmed by showing the concomitant induction of DNA damage in these cell types. Similar results were obtained in vivo, following intravenous iron administration. Secondly, using magnetic resonance imaging we show an increased iron deposition in the fingers of a patient with early SSc and nailfold microhemorrhages. While a systematic magnetic resonance study to examine tissue iron levels in SSc, including internal organs, is underway, herein we propose that iron may be a pathogenetic link between microvasculopathy and fibrosis and an additional mechanism responsible for increased oxidative stress in SSc.

Cardiovascular Magnetic Resonance as Pathophysiologic Tool in Diabetes Mellitus.

Diabetes mellitus can independently contribute to cardiovascular disease and represents a severe risk factor for premature development of cardiovascular disease. A three-fold higher mortality than the general population has been observed in type 1 diabetes mellitus whereas a two- to four-fold increased probability to develop cardiovascular disease has been observed in type 2 diabetes mellitus. Cardiovascular magnetic resonance, a non-radiative modality, is superior to all other modalities in detecting myocardial infarction. The main cardiovascular magnetic resonance sequences used include a) balanced steady-state free precession (bSSFP) for function evaluation; b) T2-W for oedema detection; c) T1 W for ischemia detection during adenosine stress; and d) late gadolinium enhanced T1-W images (LGE), evaluated 15 min after injection of paramagnetic contrast agent gadolinium, which permit the diagnosis of replacement fibrosis, which appears white in the middle of suppressed, nulled myocardium. Although LGE is the technique of choice for diagnosis of replacement fibrosis, it cannot assess diffuse myocardial fibrosis. The application of T1 mapping (native or pre contrast and post contrast) allows identification of diffuse myocardial fibrosis, which is not detectable my other means. Native T1 and Contrast-enhanced T1 mapping are involved in the extracellular volume fraction (ECV) calculation. Recently, 1H-cardiovascular magnetic resonance spectroscopy has been applied to calculate the amount of myocardial triglycerides, but at the moment it is not part of the routine assessment of diabetes mellitus. The multifaceted nature of cardiovascular magnetic resonance has the great potential of concurrent evaluation of function and myocardial ischemia/fibrosis in the same examination and represents an indispensable tool for accurate diagnosis of cardiovascular disease in diabetes mellitus.

Cardiovascular magnetic resonance in women with cardiovascular disease: position statement from the Society for Cardiovascular Magnetic Resonance (SCMR).

This document is a position statement from the Society for Cardiovascular Magnetic Resonance (SCMR) on recommendations for clinical utilization of cardiovascular magnetic resonance (CMR) in women with cardiovascular disease. The document was prepared by the SCMR Consensus Group on CMR Imaging for Female Patients with Cardiovascular Disease and endorsed by the SCMR Publications Committee and SCMR Executive Committee. The goals of this document are to (1) guide the informed selection of cardiovascular imaging methods, (2) inform clinical decision-making, (3) educate stakeholders on the advantages of CMR in specific clinical scenarios, and (4) empower patients with clinical evidence to participate in their clinical care. The statements of clinical utility presented in the current document pertain to the following clinical scenarios: acute coronary syndrome, stable ischemic heart disease, peripartum cardiomyopathy, cancer therapy-related cardiac dysfunction, aortic syndrome and congenital heart disease in pregnancy, bicuspid aortic valve and aortopathies, systemic rheumatic diseases and collagen vascular disorders, and cardiomyopathy-causing mutations. The authors cite published evidence when available and provide expert consensus otherwise. Most of the evidence available pertains to translational studies involving subjects of both sexes. However, the authors have prioritized review of data obtained from female patients, and direct comparison of CMR between women and men. This position statement does not consider CMR accessibility or availability of local expertise, but instead highlights the optimal utilization of CMR in women with known or suspected cardiovascular disease. Finally, the ultimate goal of this position statement is to improve the health of female patients with cardiovascular disease by providing specific recommendations on the use of CMR.

Cardiac amyloidosis: in search of the ideal diagnostic tool.

BACKGROUND: Cardiac amyloidosis (CA) is due to amyloid deposition in the myocardium. Transthyretin (ATTR) and light-chain (AL) amyloidosis are the main types of CA. Here, we present the clinical and imaging findings in patients with CA and discuss the controversies with the aim of finding the ideal diagnostic tool. METHODS: Ten patients suspected of having CA on the basis of electrocardiographic (ECG) and echocardiographic findings were evaluated via cardiovascular magnetic resonance imaging (CMR; 1.5 T) using cine, late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction. N­terminal pro-B-type natriuretic peptide (NT-proBNP) levels were also assessed in all patients. RESULTS: All ten patients had an echocardiogram suggestive of CA. The CMR study documented ventricular hypertrophy leading to small ventricular volumes, as assessed by echocardiography. Diffuse subendocardial LGE, supporting the diagnosis of CA, was identified in all except one patient, who had subepicardial LGE due to myocarditis that was verified by endomyocardial biopsy (EMB). Right ventricular (RV) involvement was identified in four of the ten patients, whose condition deteriorated rapidly over the next 6 months. The NT-proBNP levels were >332 pg/ml in all except two patients. Light-chain amyloidosis was identified via fat tissue biopsy in two patients and through renal biopsy in one patient. In two patients with positive technetium-99m, EMB confirmed the diagnosis of ATTR. CONCLUSION: NT-proBNP may be a sensitive but nonspecific biomarker for assessing CA. However, CMR is the only imaging modality that can assess the pathophysiologic background of cardiac hypertrophy and the severity of CA, irrespective of NT-proBNP level.

Tissue Characterization in Cardiology: Moving Beyond Function.

Cardiovascular Magnetic Resonance (CMR) offers accurate and highly reproducible tissue characterization, beyond cardiac function. Late gadolinium enhancement (LGE), although represents a noninvasive biopsy for fibrosis quantification, it is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) are able to provide important information about processes involving both myocardial cells and interstitium that otherwise cannot be identified. Changes in myocardial native T1 mapping reflect cardiac diseases such as acute coronary syndromes, myocardial infarction, myocarditis, diffuse fibrosis, systemic disease such as cardiac amyloidosis, all presented with high T1 and Anderson-Fabry disease and siderosis, presented with low T1 mapping. The ECV, an index generated by native and postcontrast T1 mapping, introduces a new way to measure the cellular and extracellular interstitial matrix (ECM). ECV has a prognostic value equal to Left ventricular ejection fraction (LVEF); however, LVEF underscores the interstitial matrix. This myocyte-ECM dichotomy has important implications for identifying therapeutic targets that are of great value for heart failure (HF) treatment. Furthermore, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset HF. These indices will affect significantly the clinical decision making. However, there is still lack of multicenter studies and community-wide approach including MRI vendors, clinicians, fundings, softwares, and contrast agent manufacturers.

Cardiac Masses: The Role of Cardiovascular Imaging in the Differential Diagnosis.

Cardiac masses are space occupying lesions within the cardiac cavities or adjacent to the pericardium. They include frequently diagnosed clinical entities such as clots and vegetations, common benign tumors such as myxomas and papillary fibroelastomas and uncommon benign or malignant primary or metastatic tumors. Given their diversity, there are no guidelines or consensus statements regarding the best diagnostic or therapeutic approach. In the past, diagnosis used to be made by the histological specimens after surgery or during the post-mortem examination. Nevertheless, evolution and increased availability of cardiovascular imaging modalities has enabled better characterization of the masses and the surrounding tissue. Transthoracic echocardiography using contrast agents can evaluate the location, the morphology and the perfusion of the mass as well as its hemodynamic effect. Transesophageal echocardiography has increased spatial and temporal resolution; hence it is superior in depicting small highly mobile masses. Cardiac magnetic resonance and cardiac computed tomography are complementary providing tissue characterization. The scope of this review is to present the role of cardiovascular imaging in the differential diagnosis of cardiac masses and to propose a step-wise diagnostic algorithm, taking into account the epidemiology and clinical presentation of the cardiac masses, as well as the availability and the incremental value of each imaging modality.

3-D optimized classification and characterization artificial intelligence paradigm for cardiovascular/stroke risk stratification using carotid ultrasound-based delineated plaque: Atheromatic™ 2.0.

BACKGROUND AND PURPOSE: Atherosclerotic plaque tissue rupture is one of the leading causes of strokes. Early carotid plaque monitoring can help reduce cardiovascular morbidity and mortality. Manual ultrasound plaque classification and characterization methods are time-consuming and can be imprecise due to significant variations in tissue characteristics. We report a novel artificial intelligence (AI)-based plaque tissue classification and characterization system. METHODS: We hypothesize that symptomatic plaque is hypoechoic due to its large lipid core and minimal collagen, as well as its heterogeneous makeup. Meanwhile, asymptomatic plaque is hyperechoic due to its small lipid core, abundant collagen, and the fact that it is often calcified. We designed a computer-aided diagnosis (CADx) system consisting of three kinds of deep learning (DL) classification paradigms: Deep Convolutional Neural Network (DCNN), Visual Geometric Group-16 (VGG16), and transfer learning, (tCNN). DCNN was 3-D optimized by varying the number of CNN layers and data augmentation frameworks. The DL systems were benchmarked against four types of machine learning (ML) classification systems, and the CADx system was characterized using two novel strategies consisting of DL mean feature strength (MFS) and a bispectrum model using higher-order spectra. RESULTS: After balancing symptomatic and asymptomatic plaque classes, a five-fold augmentation process was applied, yielding 1000 carotid scans in each class. Then, using a K10 protocol (trained to test the ratio of 90%-10%), tCNN and DCNN yielded accuracy (area under the curve (AUC)) pairs of 83.33%, 0.833 (p < 0.0001) and 95.66%, 0.956 (p < 0.0001), respectively. DCNN was superior to ML by 7.01%. As part of the characterization process, the MFS of the symptomatic plaque was found to be higher compared to the asymptomatic plaque by 17.5% (p < 0.0001). A similar pattern was seen in the bispectrum, which was higher for symptomatic plaque by 5.4% (p < 0.0001). It took <2 s to perform the online CADx process on a supercomputer. CONCLUSIONS: The performance order of the three AI systems was DCNN > tCNN > ML. Bispectrum-based on higher-order spectra proved a powerful paradigm for plaque tissue characterization. Overall, the AI-based systems offer a powerful solution for plaque tissue classification and characterization.

Is There a Brain/Heart Interaction in Rheumatoid Arthritis and Seronegative Spondyloartropathies? A Combined Brain/Heart Magnetic Resonance Imaging Reveals the Answer.

PURPOSE OF REVIEW: To present the interaction between brain/heart and emphasize the role of combined brain/heart magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and other seronegative spondyloarthropathies (SNA). RECENT FINDINGS: Both traditional cardiovascular disease (CVD) risk factors and intrinsic RA/SNA features contribute to the increased CVD-related morbidity/mortality. CVD in RA usually occurs a decade earlier than age- and sex-matched controls, and RA patients are twice more likely to develop myocardial infarction irrespective of age, history of prior CVD, and traditional CVD risk factors. RA also increases risk of non-ischemic heart failure (HF), valvular disease, and myo-pericarditis. CVD in SNA affects more commonly patients with long-standing disease. Ascending aortitis, aortic/mitral insufficiency, conduction defects, and diastolic dysfunction are the commonest findings in ankylosing spondylitis (AS). CVD is also the leading cause of death in psoriatic arthritis (PsA), due to myopericarditis, diastolic dysfunction, and valvular disease. Brain damage, due to either ischemic or hemorrhagic stroke and silent vascular damage, such as white matter hyperenhancement (WMH), is increased in both RA/SNA and may lead to cognitive dysfunction, depression, and brain atrophy. Magnetic resonance imaging (MRI) is ideal for serial brain/heart evaluation of patients with systemic diseases. RA/SNA patients are at high risk for brain/heart damage at early age, irrespectively of classic risk factors. Until more data will be obtained, a combined brain/heart MRI evaluation can be proposed in RA/SNA with new onset of arrhythmia and/or HF, cognitive dysfunction and/or depression.

Current understanding and future perspectives of brain-heart-kidney axis in psoriatic arthritis.

Psoriatic arthritis (PsA) patients are at a higher risk of systemic inflammatory sequelae, leading to microalbuminuria, cardiovascular (CVD) and neuropsychiatric (NPD) disease. Our aim is to present the existing literature about the relationship between CVD, kidney and NPD in PsA. The literature evaluation of PsA revealed that chronic T-cell activation and increased levels of circulating immune complexes can cause glomerular injury leading to microalbuminuria, which predicts CVD and all-cause mortality in both diabetic and non-diabetic patients. Furthermore, it is a marker of preclinical brain damage and identifies patients at higher risk of NPD/CVD events. Among the currently used imaging modalities in PsA, magnetic resonance imaging (MRI) maintains a crucial role, because it is ideal for concurrent evaluation of brain/heart involvement and serial follow up assessment. There is increasing evidence regarding the relationship between kidneys, heart and brain in PsA. Although currently there are no official recommendations about a combined brain/heart MRI in PsA, it could be considered in PsA with microalbuminuria, arrhythmia, HF, cognitive dysfunction and/or depression.

Integration of estimated glomerular filtration rate biomarker in image-based cardiovascular disease/stroke risk calculator: a south Asian-Indian diabetes cohort with moderate chronic kidney disease.

BACKGROUND: Recently, a 10-year image-based integrated calculator (called AtheroEdge Composite Risk Score-AECRS1.0) was developed which combines conventional cardiovascular risk factors (CCVRF) with image phenotypes derived from carotid ultrasound (CUS). Such calculators did not include chronic kidney disease (CKD)-based biomarker called estimated glomerular filtration rate (eGFR). The novelty of this study is to design and develop an advanced integrated version called-AECRS2.0 that combines eGFR with image phenotypes to compute the composite risk score. Furthermore, AECRS2.0 was benchmarked against QRISK3 which considers eGFR for risk assessment. METHODS: The method consists of three major steps: 1) five, current CUS image phenotypes (CUSIP) measurements using AtheroEdge system (AtheroPoint, CA, USA) consisting of: average carotid intima-media thickness (cIMTave), maximum cIMT (cIMTmax), minimum cIMT (cIMTmin), variability in cIMT (cIMTV), and total plaque area (TPA); 2) five, 10-year CUSIP measurements by combining these current five CUSIP with 11 CCVRF (age, ethnicity, gender, body mass index, systolic blood pressure, smoking, carotid artery type, hemoglobin, low-density lipoprotein cholesterol, total cholesterol, and eGFR); 3) AECRS2.0 risk score computation and its comparison to QRISK3 using area-under-the-curve (AUC). RESULTS: South Asian-Indian 339 patients were retrospectively analyzed by acquiring their left/right common carotid arteries (678 CUS, mean age: 54.25±9.84 years; 75.22% males; 93.51% diabetic with HbA1c ≥6.5%; and mean eGFR 73.84±20.91 mL/min/1.73m2). The proposed AECRS2.0 reported higher AUC (AUC=0.89, P<0.001) compared to QRISK3 (AUC=0.51, P<0.001) by ~74% in CKD patients. CONCLUSIONS: An integrated calculator AECRS2.0 can be used to assess the 10-year CVD/stroke risk in patients suffering from CKD. AECRS2.0 was much superior to QRISK3.

Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolaemia.

AIMS: The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in patients with homozygous familial hypercholesterolaemia. METHODS AND RESULTS: In 12 homozygous familial hypercholesterolaemia patients treated with lipid-lowering drugs ± biweekly lipoprotein apheresis sessions (nine patients), daily lomitapide was added. The lipid profile (total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol) before and after lomitapide treatment was evaluated. The follow-up period with lomitapide treatment was 3-24 months (13.8 ± 7.9). The median baseline low-density lipoprotein cholesterol level was 900 mg/dl (348-1070), after lipid-lowering drugs therapy was 383.5 mg/dl (214-866) and after lipid-lowering drugs + time-averaged level was 288 mg/dl (183.7-716.6). The addition of lomitapide lowered low-density lipoprotein cholesterol levels further by 56.8% compared to lipid-lowering drugs alone (mean reduction 262, 95% confidence interval (105.5-418.7), p = 0.005) and by 54% (mean reduction 182.9, 95% confidence interval (-342 - -23), p = 0.031) comparing to lipid-lowering drugs + lipoprotein apheresis (time-averaged level). The time-averaged level of low-density lipoprotein cholesterol in lipid-lowering drugs + lipoprotein apheresis patients compared with lipid-lowering drugs + lomitapide was 54% in favour of lomitapide (p = 0.031). CONCLUSIONS: Treatment with lomitapide in homozygous familial hypercholesterolaemia patients has a beneficial effect with a constant decrease of low-density lipoprotein cholesterol by 57% compared with classical lipid-lowering therapy and by 54% compared with classical lipid-lowering therapy and time-averaged level of low-density lipoprotein cholesterol.

Silent Myocardial Perfusion Abnormalities Detected by Stress Cardiovascular Magnetic Resonance in Antiphospholipid Syndrome: A Case-Control Study.

Objective: To examine the prevalence of silent myocardial ischemia and fibrosis in antiphospholipid syndrome (APS), using stress cardiovascular magnetic resonance (CMR). Methods: Forty-four consecutive APS patients without prior cardiac disease (22 primary APS, 22 systemic lupus erythematosus (SLE)/APS, mean age 44 (12.9) years, 64% women) and 44 age/gender-matched controls were evaluated using CMR at 1.5 T. Steady-state free precession imaging for function assessment and adenosine stress-CMR for perfusion-fibrosis evaluation were employed. The myocardial perfusion reserve index (MPRI), and myocardial fibrosis expressed as late gadolinium enhancement (LGE), were evaluated. Coronary angiography was indicated in patients with LGE. Associations with APS characteristics, classic cardiovascular disease (CVD) risk factors, high-sensitivity CRP (hs-CRP) and high-sensitivity Troponin (hs-TnT) levels were tested. All patients were followed up for 12 months. Results: Median MPRI was significantly lower in APS patients versus controls [1.5 (0.9-1.9) vs. 2.7 (2.2-3.2), p < 0.001], independently of any LGE presence. LGE was detected in 16 (36.3%) patients versus none of controls (p < 0.001); 12/16 were subsequently examined with coronary angiography and only two of them had coronary artery lesions. In multivariable analysis, none of the APS-related and classic CVD risk factors, or hs-CRP and hs-TnT covariates, were significant predictors of abnormal MPRI or LGE. At the twelve month follow-up, three (6.8%) patients experienced coronary artery disease, notably those with the lowest MPRI values. Conclusions: Abnormal MPRI and LGE are common in asymptomatic APS patients, independently so of any APS-related and classic CVD risk factors, or coronary angiography findings in cases with LGE. Stress-CMR is a valuable tool to detect silent myocardial ischemia and fibrosis in APS.

Systematic Review of PCR Proof of Parvovirus B19 Genomes in Endomyocardial Biopsies of Patients Presenting with Myocarditis or Dilated Cardiomyopathy.

BACKGROUND: Diverse viral infections have been associated with myocarditis (MC) and dilated cardiomyopathy (DCM). In this meta-analysis, we summarize the published results on the association of parvovirus B19 (B19V) genomes with human MC/DCM versus controls. METHODS: n = 197 publications referring to B19V and MC or DCM were retrieved using multiple PubMed search modes. Out of these, n = 29 publications met the inclusion criteria with data from prospective analyses on >10 unselected patients presenting with MC or DCM (dataset: MA01). Data retrieved simultaneously from both controls and MC/DCM patients were available from n = 8 from these publications (dataset: MA02). RESULTS: In the dataset MA01 B19V genomes were detected in 42.6% of the endomyocardial biopsies (EMB) in this cohort by PCR. In the dataset MA02 comprising n = 638 subjects, there was no statistically significant different rate of B19V positivity in myocardial tissues comparing controls (mean: 38.8 + 24.1%) versus the MC/DCM-patients (45.5 + 24.3%; p = 0.58). There was also no statistical difference between the positivity rate of B19V genomes in myocardial tissues of MA01 (46.0 + 19.5%) and the two patient groups of MA02 (p > 0.05). CONCLUSIONS: This systematic review reveals that the mean rate of PCR detected B19V genomes in patients presenting with MC/DCM does not differ significantly from the findings in control myocardial tissues. These data imply pathogenetically insignificant latency of B19V genomes in a proportion of myocardial tissues, both in MC-/DCM-patients and in controls. More information (i.e., replicative status, viral protein expression) is pertinent to achieve a comprehensive workup of myocardial B19V infection.

Cardio-oncology, the myth of Sisyphus, and cardiovascular disease in breast cancer survivors.

The number of breast cancer (BC) survivors has been increasing lately, due to the improvement in early detection strategies and oncological treatments. However, BC survivors are 3 times as likely to develop heart failure (HF) within 5 years of cancer diagnosis, and 7/100 of them will develop HF in a median follow-up of 8.5 years. Furthermore, HF in BC survivors has a worse prognosis compared to other causes of HF. Anthracyclines and trastuzumab have been proven to improve survival. However, they are also considered as the main causative factors of HF in BC survivors. Old patients, those with a pre-existing cardiovascular (CV) risk factors/disease, prior exposure to chemotherapy and radiotherapy are at increased risk. Serial evaluation of troponins and cardiac imaging parameters using echocardiography and cardiovascular magnetic resonance can significantly contribute to the early diagnosis of cardiac involvement before overt HF will develop. Assessment and immediate treatment of traditional CV risk factors is the first step for cardiotoxicity prevention. In BC survivors with known heart disease, the clinical stabilization is strongly recommended for cardiotoxicity prevention. Finally, in high-risk CV patients, primary prevention including cardioprotectants and/or CV drugs should be applied. According to recent studies, the early start of ACE inhibitors and ß-blockers and the modification of anti-cancer treatment can prevent the decline in left ventricular ejection fraction. However, further multicenter studies are needed to establish both prevention and treatment protocols to successfully overcome HF development in BC survivors.

Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement.

Amyloidosis is caused by extracellular deposition of insoluble abnormal fibrils constituted by misfolded proteins, which can modify tissue anatomy and hinder the function of multiple organs including the heart. Amyloidosis that can affect the heart includes mostly systemic amyloidosis (amyloid light chain, AL) and transthyretin amyloidosis (ATTR). The latter can be acquired in elderly patients (ATTRwt), or be inherited in younger individuals (ATTRm). The diagnosis is demanding given the high phenotypic heterogeneity of the disease. Therefore, "red flags," which are suggestive features giving support to diagnostic suspicion, are extremely valuable. However, the lack of broad awareness among clinicians represents a major obstacle for early diagnosis and treatment of ATTR. Furthermore, recent implementation of noninvasive diagnostic techniques has revisited the need for endomyocardial biopsy (EMB). In fact, unlike AL amyloidosis, which requires tissue confirmation and typing for diagnosis, ATTR can now be diagnosed noninvasively with the combination of bone scintigraphy and the absence of a monoclonal protein. Securing the correct diagnosis is pivotal for the newly available therapeutic options targeting both ATTRm and ATTRwt, and are directed to either stabilization of the abnormal protein or the reduction of the production of transthyretin. The purpose of this article is to review the contemporary aspects of diagnosis and management of transthyretin amyloidosis with cardiac involvement, summarizing also the recent therapeutic advances with tafamidis, patisiran, and inotersen.