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Table 1 Typical CMR fibrosis findings in common pathologies LGE T1 mapping Ischaemic cardiomyopathy Subendocardial involvement Variable transmural extension Coronary artery territory distribution Quantitative native T1 may perform similarly to LGE for detecting chronic infarction ECV and native T1 in non-infarcted myocardium appear to be elevated DCM Non-ischaemic distribution, often mid-wall/subepicardial ECV and native T1 may be elevated Aortic stenosis Typically non-ischaemic mid-wall distribution May have subendocardial involvement ECV, iECV and native T1 may be elevated Post-AVR findings vary depending on relative regression of cellular and extracellular constituents of myocardium. Hypertrophic cardiomyopathy Patchy non-ischaemic distribution in regions of focal wall thickening, or at the right ventricular insertion points in the septum ECV and native T1 may be elevated, even in patients without LGE Myocarditis At least one focal lesion in non-ischaemic distribution; often inferolateral and subepicardial Used in conjunction with T2 mapping and early gadolinium enhancement for oedema and hyperaemia Native T1 may offer greater diagnostic accuracy in myocarditis than LGE and traditional Lake Louise criteria Not specific for acute vs chronic myocarditis Cardiac amyloidosis Diffuse myocardial uptake Difficult to null images —black blood pool rather than white ECV and native T1 elevated and may quantify disease burden Cardiac sarcoidosis Non-specific appearances Multi-focal, non-ischaemic distribution is suggestive Native T1 may discriminate sarcoidosis from healthy controls Regresses with anti-inflammatory therapy AVR, aortic valve replacement; CMR, cardiovascular magnetic resonance; DCM, dilated cardiomyopathy; iECV, indexed extracellular volume; LGE, late gadolinium enhancement. ECV% represents the extracellular matrix as a proportion of total left ventricular myocardial volume, whereas iECV adjusts for left ventricular myocardial volume (ECV%×left ventricular myocardial volume) and offers a measure of absolute matrix volume.5 6 A barrier to the widespread adoption of T1 mapping has been standardisation between vendors and sequences and unclear thresholds for normal values. [...]T1 mapping is now at the forefront of myocardial imaging research.

Introduction Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease characterised by substitution of the ventricular myocardium by fibrofatty tissue.1 The disease was originally termed ‘arrhythmogenic right ventricular (dysplasia/) cardiomyopathy’ (ARVC) to define a condition which distinctively affected the right ventricle (RV) and predisposed to potentially fatal ventricular arrhythmias, particularly in young individuals and athletes.2–4 New insights arising from postmortem investigations, genotype–phenotype correlation studies and myocardial tissue characterisation by contrast-enhanced cardiac magnetic resonance (CMR) led to increased awareness that the disease often also involves the left ventricle (LV).5–11 The current designation of ‘arrhythmogenic cardiomyopathy’ better reflects the evolving concept of a heart muscle disease affecting both ventricles, with some phenotypic variants characterised by a parallel or predominant involvement of the LV. According to the HRS document, the vague common denominator of this miscellaneous group of ‘arrhythmogenic cardiomyopathies’ was the ‘clinical presentation with symptoms or documentation of atrial fibrillation, conduction disease, and/or RV and/or LV arrhythmia’. CMR studies in living patients fulfilling the 2010 International Task Force (ITF) criteria have consistently shown that LV involvement in terms of morphofunctional (LV global or regional systolic dysfunction) and/or structural (LV late gadolinium enhancement (LGE)) abnormalities is identified in more than half of patients.9 22 24 According to the available findings of clinical studies, phenotypic features of left-sided ACM include the following (figure 1): (1) ECG abnormalities such as low-amplitude QRS complexes (peak to peak <0.5 mV) in limb leads and T-wave inversion or flattening in the lateral (or inferolateral) leads, although the ECG is often normal; (2) ventricular arrhythmias with a right bundle branch block (RBBB) morphology of the ectopic QRS (denoting the origin from the LV); (3) normal or slightly depressed LV systolic function with no (or mild) dilatation; (4) large amount of myocardial fibrosis evidenced by contrast-enhanced CMR as LGE; and (5) ‘non-ischemic’ pattern of LGE, predominantly involving the subepicardial layers of the inferior and the inferolateral regions. A number of human DSP gene mutations have been linked with ACM, which manifest characteristically with early LV involvement occurring in isolation or preceding RV disease.28 Of note, in the initial report of the DSP gene mutation responsible for ‘Carvajal syndrome’, the cardiac phenotype resembled that of DCM as opposed to the classic ARVC phenotype.29 Phospholamban normally inhibits the sarcoendoplasmic reticulum calcium transport ATPase, and PLN gene mutations cause dysregulated calcium flux, predisposing to prominent arrhythmia and ventricular dysfunction.

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation.

ObjectiveTo determine the association of pulmonary valve replacement (PVR) with death and sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTOF).MethodsSubjects with rTOF and cardiac magnetic resonance from an international registry were included. A PVR propensity score was created to adjust for baseline differences. PVR consensus criteria were predefined as pulmonary regurgitation >25% and ≥2 of the following criteria: right ventricular (RV) end-diastolic volume >160 mL/m2, RV end-systolic volume >80 mL/m2, RV ejection fraction (EF) <47%, left ventricular EF <55% and QRS duration >160 ms. The primary outcome included (aborted) death and sustained VT. The secondary outcome included heart failure, non-sustained VT and sustained supraventricular tachycardia.ResultsIn 977 rTOF subjects (age 26±15 years, 45% PVR, follow-up 5.3±3.1 years), the primary and secondary outcomes occurred in 41 and 88 subjects, respectively. The HR for subjects with versus without PVR (time-varying covariate) was 0.65 (95% CI 0.31 to 1.36; P=0.25) for the primary outcome and 1.43 (95% CI 0.83 to 2.46; P=0.19) for the secondary outcome after adjusting for propensity and other factors. In subjects (n=426) not meeting consensus criteria, the HR for subjects with (n=132) versus without (n=294) PVR was 2.53 (95% CI 0.79 to 8.06; P=0.12) for the primary outcome and 2.31 (95% CI 1.07 to 4.97; P=0.03) for the secondary outcome.ConclusionIn this large multicentre rTOF cohort, PVR was not associated with a reduced rate of death and sustained VT at an average follow-up of 5.3 years. Additionally, there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.

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.

ObjectiveMitral annular disjunction (MAD) is an abnormality linked to mitral valve prolapse (MVP), possibly associated with malignant ventricular arrhythmias. We assessed the agreement among different imaging techniques for MAD identification and measurement.Methods131 patients with MVP and significant mitral regurgitation undergoing transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were retrospectively enrolled. Transoesophageal echocardiography (TOE) was available in 106 patients. MAD was evaluated in standard long-axis views (four-chamber, two-chamber, three-chamber) by each technique.ResultsConsidering any-length MAD, MAD prevalence was 17.3%, 25.5%, 42.0% by TTE, TOE and CMR, respectively (p<0.05). The agreement on MAD identification was moderate between TTE and CMR (κ=0.54, 95% CI 0.49 to 0.59) and good between TOE and CMR (κ=0.79, 95% CI 0.74 to 0.84). Assuming CMR as reference and according to different cut-off values for MAD (≥2 mm, ≥4 mm, ≥6 mm), specificity (95% CI) of TTE and TOE was 99.6 (99.0 to 100.0)% and 98.7 (97.4 to 100.0)%; 99.3 (98.4 to 100.0)% and 97.6 (95.8 to 99.4)%; 97.8 (96.2 to 99.3)% and 93.2 (90.3 to 96.1)%, respectively; sensitivity (95% CI) was 43.1 (37.8 to 48.4)% and 74.5 (69.4 to 79.5)%; 54.0 (48.7 to 59.3)% and 88.9 (85.2 to 92.5)%; 88.0 (84.5 to 91.5)% and 100.0 (100.0 to 100.0)%, respectively. MAD length was 8.0 (7.0-10.0), 7.0 (5.0-8.0], 5.0 (4.0-7.0) mm, respectively by TTE, TOE and CMR. Agreement on MAD measurement was moderate between TTE and CMR (ρ=0.73) and strong between TOE and CMR (ρ=0.86).ConclusionsAn integrated imaging approach could be necessary for a comprehensive assessment of patients with MVP and symptoms suggestive for arrhythmias. If echocardiography is fundamental for the anatomic and haemodynamic characterisation of the MV disease, CMR may better identify small length MAD as well as myocardial fibrosis.

Cardiovascular magnetic resonance (CMR) is a rapidly evolving non-invasive imaging modality offering comprehensive, multiparametric assessment of cardiac structure and function in a variety of clinical situations. Cine imaging with CMR is the gold standard non-invasive imaging technique for the quantification of ventricular volumes and systolic function. It also affords superior visualisation of apical and right ventricular morphological abnormalities. In coronary artery disease, CMR stress perfusion imaging identifies functionally significant coronary artery disease with high sensitivity and specificity, and international guidelines recommend CMR perfusion imaging in patients with chest pain at intermediate-high risk of coronary disease. Late gadolinium enhancement (LGE) imaging is the most sensitive imaging technique for identifying infarction/viability. In non-ischaemic cardiomyopathy, LGE imaging plays vital diagnostic and prognostic roles in a number of cardiomyopathies (eg, hypertrophic and dilated cardiomyopathies, and amyloidosis). In vivo tissue characterisation with CMR enables the identification of oedema/inflammation in acute coronary syndromes/myocarditis and the diagnosis of chronic fibrotic conditions (eg, in hypertrophic and dilated cardiomyopathy, aortic stenosis and amyloidosis). CMR T2* imaging uniquely offers non-invasive assessment of iron overload states, facilitating diagnosis and management. A multiparametric CMR approach also enables differentiation of cardiac masses/tumours and is a useful adjunct to echocardiography in the assessment of valve disease. The emergence of automated, inline, quantitative methodologies will expand the scope of CMR and reduce its cost in forthcoming years.

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.

ObjectivesTo compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsWe prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM.ResultsPatients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities.ConclusionTemporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.