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Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions.

Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death leading to left ventricular dysfunction. Clinical heart failure may ensue in up to 5% of high-risk patients. Improved cancer survival together with better awareness of the late effects of cardiotoxicity has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors with early intervention to treat or prevent heart failure. The main mechanism of anthracycline cardiotoxicity is now thought to be through inhibition of topoisomerase 2β resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic susceptibility factors will help identify susceptible patients in the future. Cardiac imaging with echocardiographic measurement of global longitudinal strain and cardiac troponin detect early myocardial injury prior to the development of left ventricular dysfunction. There is no consensus on how best to monitor anthracycline cardiotoxicity although guidelines advocate quantification of left ventricular ejection fraction before and after chemotherapy with additional scanning being justified in high-risk patients. Patients developing significant left ventricular dysfunction with or without clinical heart failure should be treated according to established guidelines. Liposomal encapsulation reduces anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline interferes with binding to topoisomerase 2β and reduces both cardiotoxicity and subsequent heart failure in high-risk patients. Angiotensin inhibition and β-blockade are also protective and appear to prevent the development of left ventricular dysfunction when given prior or during chemotherapy in patients exhibiting early signs of cardiotoxicity.

ObjectiveTo explore the association between three-dimensional (3D) cardiac magnetic resonance (CMR) feature tracking (FT) right ventricular peak global longitudinal strain (RVpGLS) and major adverse cardiovascular events (MACEs) in patients with stage C or D heart failure (HF) with non-ischaemic dilated cardiomyopathy (NIDCM) but without atrial fibrillation (AF).MethodsPatients with dilated cardiomyopathy were enrolled in this prospective cohort study. Comprehensive clinical and biochemical analysis and CMR imaging were performed. All patients were followed up for MACEs.ResultsA total of 192 patients (age 53±14 years) were eligible for this study. A combination of cardiovascular death and cardiac transplantation occurred in 18 subjects during the median follow-up of 567 (311, 920) days. Brain natriuretic peptide, creatinine, left ventricular (LV) end-diastolic volume, LV end-systolic volume, right ventricular (RV) end-diastolic volume and RVpGLS from CMR were associated with the outcomes. The multivariate Cox regression model adjusting for traditional risk factors and CMR variables detected a significant association between RVpGLS and MACEs in patients with stage C or D HF with NIDCM without AF. Kaplan-Meier analysis based on RVpGLS cut-off value revealed that patients with RVpGLS <−8.5% showed more favourable clinical outcomes than those with RVpGLS ≥−8.5% (p=0.0037). Subanalysis found that this association remained unchanged.ConclusionsRVpGLS-derived from 3D CMR FT is associated with a significant prognostic impact in patients with NIDCM with stage C or D HF and without AF.

ObjectiveTo assess the utility of machine learning algorithms for automatically estimating prognosis in patients with repaired tetralogy of Fallot (ToF) using cardiac magnetic resonance (CMR).MethodsWe included 372 patients with ToF who had undergone CMR imaging as part of a nationwide prospective study. Cine loops were retrieved and subjected to automatic deep learning (DL)-based image analysis, trained on independent, local CMR data, to derive measures of cardiac dimensions and function. This information was combined with established clinical parameters and ECG markers of prognosis.ResultsOver a median follow-up period of 10 years, 23 patients experienced an endpoint of death/aborted cardiac arrest or documented ventricular tachycardia (defined as >3 documented consecutive ventricular beats). On univariate Cox analysis, various DL parameters, including right atrial median area (HR 1.11/cm², p=0.003) and right ventricular long-axis strain (HR 0.80/%, p=0.009) emerged as significant predictors of outcome. DL parameters were related to adverse outcome independently of left and right ventricular ejection fraction and peak oxygen uptake (p<0.05 for all). A composite score of enlarged right atrial area and depressed right ventricular longitudinal function identified a ToF subgroup at significantly increased risk of adverse outcome (HR 2.1/unit, p=0.007).ConclusionsWe present data on the utility of machine learning algorithms trained on external imaging datasets to automatically estimate prognosis in patients with ToF. Due to the automated analysis process these two-dimensional-based algorithms may serve as surrogates for labour-intensive manually attained imaging parameters in patients with ToF.

Right ventricular (RV) size and function are important predictors of cardiovascular morbidity and mortality in patients with various conditions. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest. Although conventional echocardiography is widely used, its limitations in RV assessment are well recognised. New techniques such as three-dimensional and speckle tracking echocardiography have overcome the limitations of conventional echocardiography allowing a comprehensive, quantitative assessment of RV geometry and function without geometric assumptions. Cardiac magnetic resonance (CMR) and CT provide accurate assessment of RV geometry and function, too. In addition, tissue characterisation imaging for myocardial scar and fat using CMR and CT provides important information regarding the RV that has clinical applications for diagnosis and prognosis in a broad range of cardiac conditions. Limitations also exist for these two advanced modalities including availability and patient suitability for CMR and need for contrast and radiation exposure for CT. Hybrid imaging, which is able to integrate anatomical information (usually obtained by CT or CMR) with physiological and molecular data (usually obtained with positron emission tomography), can provide optimal in vivo evaluation of Rv functional impairment. This review summarises the clinically useful applications of advanced echocardiography techniques, CMR and CT for comprehensive assessment of RV size, function and mechanics.

ObjectiveIn patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM.Methods101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE.ResultsIn HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R2 for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001).ConclusionsMicrovascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker.

Radionuclide imaging remains an essential component of modern cardiology. There is overlap with the information from other imaging techniques, but no technique is static and new developments have expanded its role. This review focuses on ischaemic heart disease, heart failure, infection and inflammation. Radiopharmaceutical development includes the wider availability of positron emission tomography (PET) tracers such as rubidium-82, which allows myocardial perfusion to be quantified in absolute terms. Compared with alternative techniques, myocardial perfusion scintigraphy PET and single photon emission computed tomography (SPECT) have the advantages of being widely applicable using exercise or pharmacological stress, full coverage of the myocardium and a measure of ischaemic burden, which helps to triage patients between medical therapy and revascularisation. Disadvantages include the availability of expertise in some cardiac centres and the lack of simple SPECT quantification, meaning that global abnormalities can be underestimated. In patients with heart failure, despite the findings of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, there are still data to support the assessment of myocardial hibernation in predicting when abolition of ischaemia might lead to improvement in ventricular function. Imaging of sympathetic innervation is well validated, but simpler markers of prognosis mean that it has not been widely adopted. There are insufficient data to support its use in predicting the need for implanted devices, but non-randomised studies are promising. Other areas where radionuclide imaging is uniquely valuable are detection and monitoring of endocarditis, device infection, myocardial inflammation in sarcoidosis, myocarditis and so on, and reliable detection of deposition in suspected transthyretin-related amyloidosis.

This review gives examples of emerging cardiovascular magnetic resonance (CMR) techniques and applications that have the potential to transition from research to clinical application in the near future. Four-dimensional flow CMR (4D-flow CMR) allows time-resolved three-directional, three-dimensional (3D) velocity-encoded phase-contrast imaging for 3D visualisation and quantification of valvular or intracavity flow. Acquisition times of under 10 min are achievable for a whole heart multidirectional data set and commercial software packages are now available for data analysis, making 4D-flow CMR feasible for inclusion in clinical imaging protocols. Diffusion tensor imaging (DTI) is based on the measurement of molecular water diffusion and uses contrasting behaviour in the presence and absence of boundaries to infer tissue structure. Cardiac DTI is capable of non-invasively phenotyping the 3D micro-architecture within a few minutes, facilitating transition of the method to clinical protocols. Hybrid positron emission tomography-magnetic resonance (PET-MR) provides quantitative PET measures of biological and pathological processes of the heart combined with anatomical, morphological and functional CMR imaging. Cardiac PET-MR offers opportunities in ischaemic, inflammatory and infiltrative heart disease.

Speckle tracking echocardiography (STE) is a second-level echocardiographic technique which has gradually gained relevance in the last years. It allows semi-automatic quantification of myocardial deformation and function, overcoming most of the limitations characterizing basic echocardiography and providing an early detection of cardiac impairment. Today, its feasibility and usefulness are highly supported by literature. In particular, several studies demonstrated that STE could provide additional prognostic information beyond conventional echocardiographic and traditional clinical parameters. Moreover, a recent standardization of speckle tracking analysis regarding all cardiac chambers paved the way for the integration of STE in diagnostic and prognostic protocols for particular clinical settings. The aim of this review is to describe the prognostic role of STE in different clinical scenarios basing on currently available evidence.