Association and diagnostic utility of diastolic dysfunction and myocardial fibrosis in patients with Fabry disease

Abstract

ObjectivesCurrent guidelines highlight important therapy implications of cardiac fibrosis in patients with Fabry disease (FD). However, association between morphological and functional impairments with cardiac fibrosis in hereditary cardiomyopathies remains elusive. We investigated the association between echocardiography-determined cardiac dysfunction and cardiac MRI (cMRI)-detected myocardial fibrosis (late gadolinium enhancement, LE) in patients with FD with preserved left ventricular ejection fraction (≥50%).Methods146 patients with FD (aged 39±14 years, 57 men) were analysed, all receiving echocardiography and cMRI within a 1 week interval. Longitudinal systolic strain (LS_sys), strain rate (LSr_sys) and diastolic strain rate (LSr_E/LSr_A) were assessed using speckle-tracking imaging. Receiver operating characteristic (ROC) analysis was performed to identify the diagnostic performance of various markers for LE.ResultsLE was detected in 57 (39%) patients with FD. LV wall thickness, left atrial volume, septal E/e′, diastolic dysfunction grade, global LS_sys and E/LSr_E, mid-lateral LS_sys and LSr_E, as well as N-terminal pro-brain natriuretic peptide were all associated with LE independent of age, sex, body mass index, New York Heart Association functional class and kidney function. In ROC curve analysis, septal E/e′ performed best (area under the curve=0.86, 95% CI=0.79 to 0.92). Septal E/e′>14.8 was strongly associated with LE (specificity=97.8% and sensitivity=49.1%). In 9% of patients, localised LE was present even though no other cardiac or kidney abnormalities were detected.ConclusionsEchocardiography-derived diastolic dysfunction is closely linked to LE in FD. Septal E/e′ ratio is the best echocardiographic marker suggestive of LE. Diastolic dysfunction is not a prerequisite for LE in FD, since LE can be detected in the absence of measurable cardiac functional impairments.Trial registration numberClinicalTrials.gov Identifier (NCT03362164).

An expert consensus document on the management of cardiovascular manifestations of Fabry disease

“…Plasma N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) is elevated in patients with cardiac manifestations and correlates with symptom class, echocardiographic surrogates of elevated LV filling pressure (left atrial size and E/e′) and LV mass. Although NT‐proBNP concentrations may be raised in patients without echocardiographic evidence of LVH, the highest values are encountered in patients with LVH, diastolic dysfunction, reduced T1 relaxation times on CMRI mapping and myocardial fibrosis 183–185 . Elevated high sensitivity troponin indicates advanced disease and a worse prognosis 186 ( Table 2 ) 1,13,76,81,90,104,111,112,156,157,161,167,169,170,178,184,186–215 .…”

Fabry Disease and the Heart: A Comprehensive Review

“…Diastolic function is abnormal in 69.4% of those with LVH [4] and 63% of those wit LGE [77]. Diastolic dysfunction occurs more commonly as an abnormal relaxation or pseudonormal pattern [25], and it has been associated with the presence of LGE [78] an to correlate with NT-proBNP [79]. LV systolic dysfunction with reduction in ejection fra tion is rare (6.7%) [80], occurring in late stages of advanced Fabry cardiomyopathy [22,25 LV systolic and diastolic dysfunction can, however, be detected before the develop ment of LVH, not only by TDI [81] but also by speckle-tracking [82,83].…”

Cardiac Imaging in Anderson-Fabry Disease: Past, Present and Future

“…Diastolic dysfunction leads to the enlargement of the left atrium. In AFD, left atrial dilation occurs in the early stages of Fabry disease, even before the development of LVH [ 39 , 40 , 41 ]. Atrial damage may be the consequence of the accumulation of glycosphingolipids that has also been reported in atrial myocytes [ 42 ].…”