Pattern and prognostic value of cardiac involvement in patients with late-onset pompe disease: a comprehensive cardiovascular magnetic resonance approach

Abstract

BackgroundPompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal α–1,4-glucosidase leading to accumulation of glycogen in target tissues with progressive organ failure. While the early infantile-onset form is characterized by early severe hypertrophic cardiomyopathy with cardiac and respiratory failure, clinically relevant cardiomyopathy seems to be uncommon in patients with late-onset Pompe disease, and the prevalence and nature of myocardial abnormalities are still to be clarified.MethodsSeventeen patients with genetically proven late-onset Pompe disease (50 ± 18 years, 11 male) and 18 age- and gender-matched healthy controls (44 ± 10 year, 12 male) underwent comprehensive cardiovascular magnetic resonance (CMR) including conventional and advanced techniques: cine and feature tracking-based strain imaging for depiction of (even subtle) systolic LV dysfunction as well as late gadolinium enhancement (LGE) and myocardial extracellular volume fraction (ECV) quantification for focal and diffuse fibrosis detection.ResultsAll patients had normal left ventricular (LV) and right ventricular (RV) volumes and normal LV and RV ejection fraction. In comparison to healthy controls, neither conventional cine nor advanced feature-tracking based-strain imaging could depict any (subclinical) myocardial systolic dysfunction. Three (18%) of the patients had non-ischemic LGE in the basal inferolateral wall and 21% demonstrated elevated global ECV values suggestive of interstitial myocardial fibrosis. Non-specific abnormalities such as left atrial (LA) dilatation were present in two patients, while LV hypertrophy was seen only in one. Two of the three LGE-positive patients were also hypertensive and demonstrated high global ECV values (>30%) in addition to dilated LA. After a median follow-up of 25 (11–29) months, only one cardiovascular event occurred: one of the LGE-positive patients with a high cardiovascular risk profile suffered an acute coronary syndrome.ConclusionIn contrast to the early infantile-onset form of Pompe disease, mild and rather non-specific cardiac abnormalities can be detected by CMR only in a small proportion of patients with late-onset Pompe disease. The observed structural abnormalities seem to result from an interplay between the storage disease and other comorbidities and they did not affect short-term to mid-term prognosis in adult Pompe patients.

Cardiovascular Magnetic Resonance for the Differentiation of Left Ventricular Hypertrophy

“…These conditions are often progressive and may manifest extreme hypertrophic phenotypes. Given their rarity, there is little data available on using advanced cardiac imaging to differentiate them from other causes of LVH [92,93]. For now, genetic testing, particularly in the presence of clinical 'red flags', provides the greatest diagnostic and prognostic information for these rarer presentations [94].…”

Review of Journal of Cardiovascular Magnetic Resonance (JCMR) 2015-2016 and transition of the JCMR office to Boston

“…Pompe disease is an autosomal recessive disorder caused by a deficiency of the lysosomal alpha-1,4-glucosidease which leads to an accumulation of glycogen in target tissue and progressive organ failure. Boentert and co-workers [ 35 ] studied 17 patients with genetically proven late-onset Pompe disease (50 +/− 18 years; 11 men) and 18 age and gender matched controls with CMR. They found that all Pompe Disease patients had normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction and feature tracking measures of left ventricular strain.…”

Journal of Cardiovascular Magnetic Resonance 2017

“…Cardiac phenotyping continues to be a primary clinical indication for CMR and continues to be mainstream for the evaluation of patients presenting with a newly recognized cardiomyopathy including hypertrophic cardiomyopathy (HCM) [5, 6], Anderson-Fabry disease [7], cardiac amyloid [8, 9], non-ischemic cardiomyopathy [10–12], muscular dystrophies [13–16], non-compaction [17], Chagas [18], Pompe Disease [19], obesity [20], connective tissue disorders [21, 22], arrhythmic right ventricular cardiomyopathy [23], and Syndrome X [24]. In 2017, we found increasing focus on parametric mapping and feature tracking/strain in cardiomyopathies.…”