Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

These data suggest that myocyte storage starts in childhood and accumulates faster in men before triggering 2 processes: a sex-independent scar/inflammation regional response (LGE) and, in men, apparent myocyte hypertrophy diluting the T1 lowering of sphingolipid.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD.

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IntroductionDetecting early cardiac involvement in Fabry disease (FD) is important because therapy may alter disease progression. Cardiovascular magnetic resonance (CMR) can detect T1 lowering, representing myocardial sphingolipid storage. In many diseases, early mechanical dysfunction may be detected by abnormal global longitudinal strain (GLS). We explored the relationship of early mechanical dysfunction and sphingolipid deposition in FD.MethodsAn observational study of 221 FD and 77 healthy volunteers (HVs) who underwent CMR (LV volumes, mass, native T1, GLS, late gadolinium enhancement), ECG and blood biomarkers, as part of the prospective multicentre Fabry400 study.ResultsAll FD had normal LV ejection fraction (EF 73%±8%). Mean indexed LV mass (LVMi) was 89±39 g/m2 in FD and 55.6±10 g/m2 in HV. 102 (46%) FD participants had left ventricular hypertrophy (LVH). There was a negative correlation between GLS and native T1 in FD patients (r=−0.515, p<0.001). In FD patients without LVH (early disease), as native T1 reduced there was impairment in GLS (r=−0.285, p<0.002). In the total FD cohort, ECG abnormalities were associated with a significant impairment in GLS compared with those without ECG abnormalities (abnormal: −16.7±3.5 vs normal: −20.2±2.4, p<0.001).ConclusionsGLS in FD correlates with an increase in LVMi, storage and the presence of ECG abnormalities. In LVH-negative FD (early disease), impairment in GLS is associated with a reduction in native T1, suggesting that mechanical dysfunction occurs before evidence of sphingolipid deposition (low T1).Trial registration number NCT03199001; Results.

BackgroundConventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE.MethodsOne hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made.ResultsA total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p < 0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p < 0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction.ConclusionsDB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

Background: Fabry disease (FD) is an X-linked lysosomal storage disease resulting in tissue accumulation of sphingolipids. Key myocardial processes that lead to adverse outcomes in FD include storage, hypertrophy, inflammation and fibrosis. These are quantifiable by multi-parametric Cardiovascular Magnetic Resonance (CMR). Recent developments in CMR perfusion mapping allow rapid in-line perfusion quantification permitting broader clinical application, including the assessment of microvascular dysfunction. We hypothesized that microvascular dysfunction in FD would be associated with storage, fibrosis and oedema. Methods: A prospective, observational study of 44 FD patients (49 years, 43% male, 24 (55%) with left ventricular hypertrophy (LVH)) and 27 healthy controls with multi-parametric CMR including vasodilator stress perfusion mapping. Myocardial blood flow (MBF) was measured and its associations with other processes investigated. Results: Compared to LVH-FD, LVH+ FD had higher LV ejection fraction (73% vs 68%), more LGE (85% vs 15%) and a lower stress MBF (1.76 vs 2.36ml/g/min). The reduction in stress MBF was more pronounced in the subendocardium than subepicardium. LVH-FD had lower stress MBF than controls (2.36 vs 3.00ml/g/min, p=0.002). Across all FD, LGE and low native T1 were independently associated with reduced stress MBF. On a per-segment basis stress MBF was independently associated with wall thickness, T2, ECV and LGE. Conclusions: FD patients have reduced perfusion, particularly in the subendocardium with greater reductions with LVH, storage, edema and scar. Perfusion is reduced even without LVH suggesting it is an early disease marker. Clinical perspective Fabry disease (FD) is a slowly progressive multisystem storage disease. Progressive cardiac involvement is the primary cause of premature death. Therapy is available but expensive. Myocardial phenotype development and pathways is not well understood and the impact of treatment and the timing of initiation is uncertain. Recently, cardiovascular magnetic resonance has begun to unravel phenotype development because, as well as hypertrophy and fibrosis (using late gadolinium enhancement), storage can now be measured (using T1 mapping) and edema/inflammation (using T2 mapping). Microvascular dysfunction is also thought also to play a role. CMR perfusion mapping can now quantify thisboth concurrently with the other assessments and without using ionizing radiation, more easily permitting the assessment of early disease. We performed multi-parametric CMR in FD including perfusion mapping. Compared to healthy volunteers, patients with FD had reduced stress myocardial blood flow (MBF). This occurred even before hypertrophy. It was most marked subendocardially, was worse when there was storage and, regionally, where there was fibrosis. This implies that microvascular dysfucntion is an early disease feature and could contribute to the progression from storage to fibrosis (and hence heart failure and arrhythmia). Because it may relate to endothelial rather t...