[Show abstract][Hide abstract] ABSTRACT: Cardiovascular magnetic resonance (CMR) derived native myocardial T1 is decreased in patients with Fabry disease even before left ventricular hypertrophy (LVH) occurs and may be the first non-invasive measure of myocyte sphingolipid storage. The relationship of native T1 lowering prior to hypertrophy and other candidate early phenotype markers are unknown. Furthermore, the reproducibility of T1 mapping has never been assessed in Fabry disease.
Sixty-three patients, 34 (54%) female, mean age 48 ± 15 years with confirmed (genotyped) Fabry disease underwent CMR, ECG and echocardiographic assessment. LVH was absent in 25 (40%) patients. Native T1 mapping was performed with both Modified Look-Locker Inversion recovery (MOLLI) sequences and a shortened version (ShMOLLI) at 1.5 Tesla. Twenty-one patients underwent a second scan within 24 hours to assess inter-study reproducibility. Results were compared with 63 healthy age and gender-matched volunteers.
Mean native T1 in Fabry disease (LVH positive), (LVH negative) and healthy volunteers was 853 ± 50 ms, 904 ± 46 ms and 968 ± 32 ms (for all p < 0.0001) by ShMOLLI sequences. Native T1 showed high inter-study, intra-observer and inter-observer agreement with intra-class correlation coefficients (ICC) of 0.99, 0.98, 0.97 (ShMOLLI) and 0.98, 0.98, 0.98 (MOLLI). In Fabry disease LVH negative individuals, low native T1 was associated with reduced echocardiographic-based global longitudinal speckle tracking strain (-18 ± 2% vs -22 ± 2%, p = 0.001) and early diastolic function impairment (E/E' = 7 [6-8] vs 5 [5-6], p = 0.028).
Native T1 mapping in Fabry disease is a reproducible technique. T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography.
Journal of Cardiovascular Magnetic Resonance 12/2014; 16:99. · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background—Sarcomere protein mutations in hypertrophic cardiomyopathy (HCM) induce subtle cardiac structural changes prior to the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic HCM pre-LVH (G+LVH−).
Methods and Results—A multi-centre case-control study investigated crypts and 22 other cardiovascular magnetic resonance (CMR) parameters in subclinical HCM to determine their strength of association with sarcomere gene mutation carriage. The G+LVH− sample (n=73) was 29±13 years old and 51% male. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5, 95% confidence interval [CI] 0.5-4.4, p=0.014; for ≥2 crypts, β=3.0, 95%CI 0.8-7.9, p=0.004). In combination with 3 other parameters: anterior mitral valve leaflet (AMVL) elongation (β=2.1, 95%CI 1.7-3.1, p<0.001), abnormal LV apical trabeculae (β=1.6, 95%CI 0.8-2.5, p<0.001), and smaller LV end-systolic volumes (β=1.4, 95%CI 0.5-2.3, p=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95%CI 0.8-0.9). In this G+LVH− population cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared to the other combined mutations (47 vs. 23%; odds ratio, 2.9; 95%CI 1.1-7.9; p=0.045).
Conclusions—The subclinical HCM phenotype measured by CMR in a multi-center environment and consisting of crypts (particularly multiple), AMVL elongation, abnormal trabeculae and smaller LV systolic cavity, is indicative of the presence of sarcomere gene mutations and highlights the need for further study.
[Show abstract][Hide abstract] ABSTRACT: Left ventricular noncompaction (LVNC) is characterised by prominent ventricular myocardial trabeculations, composed of sheets of cardiomyocytes. They form early during cardiogenesis but their development is complex. Measuring trabecular complexity in animal models of cardiac disease is important as abnormal trabecular patterns are increasingly been recognised to coexist with several other cardiac conditions, not just LVNC. We describe an innovative approach that utilises fractal algorithms and high-resolution episcopic microscopy (HREM) to study the developmental timing of myocardial trabeculation in mouse and we validate it using a recently described LVNC mouse model (NOTCH pathway regulator Mib1 mutant).
[Show abstract][Hide abstract] ABSTRACT: -Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy (HCM). Subtle abnormalities of the myocardium may be present in mutation carriers without hypertrophy (G+LVH-) but are difficult to quantify. Fractal analysis has been used to define trabeculae in LV noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance (CMR) images are abnormal in G+LVH- patients providing a preclinical marker of disease in HCM.
-CMR was performed on 40 G+LVH- patients (33±15yrs, 38% men), 67 patients with a clinical diagnosis of HCM (53±15yrs, 76% men; 31 with a pathogenic mutation (G+LVH+)) and 69 matched healthy volunteers (44±15yrs, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension (FD) - a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH- patients apical LV trabeculation was increased compared to controls (maximal apical FD, 1.249±0.07 vs 1.199±0.05, P=0.001). In G+LVH+ and G-LVH+ cohorts, maximal apical FD was greater than in controls (P<0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G-LVH+: 1.380±0.09). Compared to controls, G+LVH- patients also had a higher frequency of clefts (28 vs 8%, P=0.02), longer anterior mitral valve leaflets (23.5±3.0 vs 19.7±3.1mm, P<0.0001), greater septal systolic wall thickness (12.6±3.2 vs 11.2±2.1mm, P=0.03), higher ejection fraction (71±4 vs 69±4 %, P=0.03) and smaller end-systolic volumes (38±9 vs 43±12mls, P=0.03).
-Increased myocardial trabecular complexity is one of several preclinical abnormalities in HCM sarcomere gene mutation carriers without LVH.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Left ventricular noncompaction (LVNC) is a myocardial disorder characterized by excessive left ventricular (LV) trabeculae. Current methods for quantification of LV trabeculae have limitations. The aim of this study is to describe a novel technique for quantifying LV trabeculation using cardiovascular magnetic resonance (CMR) and fractal geometry. Observing that trabeculae appear complex and irregular, we hypothesize that measuring the fractal dimension (FD) of the endocardial border provides a quantitative parameter that can be used to distinguish normal from abnormal trabecular patterns. METHODS: Fractal analysis is a method of quantifying complex geometric patterns in biological structures. The resulting FD is a unitless measure index of how completely the object fills space. FD increases with increased structural complexity. LV FD was measured using a box-counting method on CMR short-axis cine stacks. Three groups were studied: LVNC (defined by Jenni criteria), n=30(age 41+/-13; men, 16); healthy whites, n=75(age, 46+/-16; men, 36); healthy blacks, n=30(age, 40+/-11; men, 15). RESULTS: In healthy volunteers FD varied in a characteristic pattern from base to apex along the LV. This pattern was altered in LVNC where apical FD were abnormally elevated. In healthy volunteers, blacks had higher FD than whites in the apical third of the LV (maximal apical FD: 1.253+/-0.005 vs. 1.235+/-0.004, p<0.01)(mean+/-s.e.m.). Comparing LVNC with healthy volunteers, maximal apical FD was higher in LVNC (1.392+/-0.010, p<0.00001). The fractal method was more accurate and reproducible (ICC, 0.97 and 0.96 for intra and inter-observer readings) than two other CMR criteria for LVNC (Petersen and Jacquier). CONCLUSIONS: FD is higher in LVNC patients compared to healthy volunteers and is higher in healthy blacks than in whites. Fractal analysis provides a quantitative measure of trabeculation and has high reproducibility and accuracy for LVNC diagnosis when compared to current CMR criteria.
Journal of Cardiovascular Magnetic Resonance 05/2013; 15(1):36. · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: -Anderson Fabry disease (AFD) is a rare but under-diagnosed intracellular lipid disorder which can cause left ventricular hypertrophy (LVH). Lipid is known to shorten the MRI parameter T1. We hypothesised that non-contrast T1 mapping by cardiovascular magnetic resonance would provide a novel and useful measure in this disease with potential to detect early cardiac involvement and distinguish AFD LVH from other causes. METHODS AND RESULTS: -227 subjects were studied: AFD patients (n=44, 55% with LVH), healthy volunteers (n=67, 0% with LVH), hypertension (n=41, 24% with LVH), hypertrophic cardiomyopathy (n=34, 100% with LVH), severe aortic stenosis (n=21, 81% with LVH) and definite AL cardiac amyloidosis (n=20, 100% with LVH). T1 mapping was performed using the Sh-MOLLI sequence on a 1.5T magnet before gadolinium administration with primary results derived from the basal and mid septum. Compared to health volunteers, septal T1 was lower in AFD and higher in other diseases (AFD vs healthy volunteers vs other patients, 882±47ms, 968±32ms, 1018±74ms, P<0.0001). In patients with LVH (n=105), T1 discriminated completely between AFD and other diseases with no overlap. In AFD, T1 correlated inversely with wall thickness (R=-0.51, P=0.0004) and was abnormal in 40% of subjects who did not have LVH. Segmentally, AFD showed pseudo-normalisation or elevation of T1 in the LV infero-lateral wall, correlating with the presence or absence of late gadolinium enhancement (1001±82ms vs 891±38ms, P<0.0001) CONCLUSIONS: -Non-contrast T1 mapping shows potential as a unique and powerful measurement in the imaging assessment of left ventricular hypertrophy and Anderson Fabry disease.
[Show abstract][Hide abstract] ABSTRACT: A spongiform epidemic is upon us - myocardial trabeculae are everywhere as left ventricular noncompaction (LVNC) ingratiates itself into modern day cardiology. Current understanding of the condition is evolving but remains incomplete, and brings to mind the chronicles of another great cardiac story: mitral valve prolapse. Anecdote suggests that many individuals with prominent trabeculae may be being falsely labelled with a disease - LVNC - using poor echocardiographic and cardiovascular magnetic resonance criteria. Until we have robust diagnostic criteria, aetiology, clinicopathological significance and prognosis, the risk of casualties from ascertainment bias will remain. We should look to history and learn from past mistakes - specifically from the mitral valve prolapse story to show the way forward for LVNC. Meanwhile, clinicians (and patients) should be wary, bearing in mind the possibility that they might be seeing LVNNC - left ventricular non-noncompaction.
International journal of cardiology 05/2012; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In reply to the letter by Finsterer and Stöllberger entitled "Consensus on unsolved issues of hypertrabeculation/noncompaction is warranted," the authors reaffirm the need for a concordant opinion on the unsolved issues which still loom over the diagnostic and clinical facets of left ventricular non-compaction. Subjects known to have ventricular hypertrabeculation and who subsequently experience a thromboembolic event should still be meticulously screened for other commoner and possibly co-existent embolic sources. In the absence of systolic dysfunction left ventricular non-compaction alone is not an indication for oral anticoagulation in so far as the primary prevention for thromboembolism is concerned. There exists no exact proof that the degree of inotropic dysfunction in hypertrabeculated hearts is directly and solely related to the extent of the non-compaction. Subendocardial perfusion deficits; diminished coronary blood flow reserve; trabecular fibrosis and aberrations at the cellular level may also be responsible for affecting ventricular systolic function. Early neurological referral is indicated following the diagnosis of non-compaction with the aim of screening for the many disorders known to be associated with this condition and genetic screening tests are best resorted to only if clinical examination fails to expose a relevant syndrome. The current cardiac magnetic resonance diagnostic criteria for non-compaction still have some important limitations which beckon a unifying consensus.
International journal of cardiology 12/2009; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Left ventricular non-compaction (LVNC) is a rare disorder that results in multiple deep trabeculations within the left ventricular myocardium. It is thought to be due in part, to an arrest of myocardial development but more recent evidence suggests that some cases may actually be acquired while other isolated cases have regressed with time. Transthoracic echocardiography remains the imaging modality of choice for LVNC where diagnosis is based on the identification of multiple prominent ventricular trabeculations with intertrabecular spaces communicating with the ventricular cavity. There is a broad and potentially confusing spectrum of clinical symptomatology in patients with ventricular non-compaction meaning that the primary diagnosis is often missed. Complications such as potentially malignant arrhythmias, left ventricular failure, and cardioembolic events arising as a result of non-compaction must be treated in an attempt to decrease morbidity and mortality from this disorder. The ultimate outcome for patients remains unclear with some boasting a prolonged asymptomatic course, to others displaying a rapid deterioration of left ventricular systolic function, leading to heart transplantation or death. In conclusion, LVNC while remaining a rare cardiomyopathy, shall probably be diagnosed with increasing frequency in the coming years because of heightened awareness about its natural history and clinical manifestations and because of the improved modalities available for cardiac imaging.
International journal of cardiology 09/2009; 140(2):145-53. · 6.18 Impact Factor