Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

BACKGROUND: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. METHODS AND RESULTS: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and ß-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with ß-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. CONCLUSIONS: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Effectiveness of clinical scores in predicting coronary artery disease in familial hypercholesterolemia: a coronary computed tomography angiography study.

PURPOSE: One of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH. MATERIAL AND METHODS: One-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA. MFHS, FHRS, SAFEHEART-RE and DLCN were assessed for each patient. Atherosclerotic burden scores at CCTA (Agatston score [AS], segment stenosis score [SSS]) and CAD-RADS score were calculated and compared to clinical indices. RESULTS: Non-obstructive CAD was found in 109 patients, while 30 patients had a CAD-RADS ≥ 3. Classifying the two groups according to AS, values varied significantly for MFHS (p < 0.001), FHRS (p < 0.001) and SAFEHEART-RE (p = 0.047), while according to SSS only MFHS and FHRS showed significant differences (p < 0.001). MFHS, FHRS and SAFEHEART-RE, but not DLCN, showed significant differences between the two CAD-RADS groups (p < .001). MFHS proved to have the best discriminatory power (AUC = 0.819; 0.703-0.937, p < 0.001) at ROC analysis, followed by FHRS (AUC = 0.795; 0.715-0.875, p < .0001) and SAFEHEART-RE (AUC = .725; .61-.843, p < .001). CONCLUSIONS: Greater values of MFHS, FHRS and SAFEHEART-RE are associated to higher risk of obstructive CAD and might help to select asymptomatic patients that should be referred to CCTA for secondary prevention.

Giant caseous mitral annular calcification mimicking ventricular pseudoaneurysm.

An 82-year-old woman with precordial pain at rest was admitted to the Emergency Department for possible cardiac heart disease; electrocardiogram excluded ischemia and high-sensitive troponin was normal. Echocardiogram revealed a hyperechoic mass adjacent to the mitral annulus. Electrocardiography-gated computed tomography (CT) angiography exam confirmed the presence of the mass protruding into the atrioventricular groove, adjacent to the posterior mitral. On the precontrast images the lesion was hyperdense with some scattered central calcific spots. CT findings are typical of a giant caseous calcification of the mitral annulus and excluded the diagnoses of pseudoaneurysm (it does not show any communication with the left ventricular cavity), neoplasm/abscess (complete caseous/calcified content) or infected/abscessified mitral calcification (absence of internal hypodense core). This is a benign condition that can be easily misdiagnosed as ventricular aneurysm or pseudoaneurysm on the contrast-enhanced images, when the caseous content is isodense to the iodinated blood pool.

Radiological outpatient' visits to avoid inappropriate cardiac CT examinations: an 8-year experience report.

PURPOSE: The aim of this study was to evaluate the appropriateness of the cardiac computed tomography angiography (CCTA) prescriptions according to the "2010-Appropriate-Use-Criteria-for-Cardiac-Computed-Tomography-Angiography" (AUCCTA) and "Clinical-indication-for-CCTA" (CICCTA) among different specialities (Cardiologist [CA], General Practitioner [GP], Other Specialists [OS]) and prescribers' age. MATERIALS AND METHODS: This is a single-centre, single-arm, cohort study. We prospectively enrolled 815 patients (October 2012-May 2019) who underwent a radiological outpatient visit, before CCTA examination. Prescriptions to the examination were categorized as follows: Appropriate (A), Uncertain (U) and Inappropriate (Ina), according to AUCCTA and I, II, III and Inv for CICCTA. This categorization was stratified according to CA, GP and OS and prescribers' age. CCTA was performed in patients whom indications belong to A/U categories. RESULTS: Eight hundred and fifteen CCTA prescriptions were analysed. An yearly increase in prescriptions was found in the eight-year observational period (2012/2019 projection: 72 vs 223). Considering AUCCTA, indication A was 540/815 (66.3%), indication U was 113/815 (13.9%) and Ina accounted for 162/815 (19.9%; 128/162 [79.0%] indications with stress test listed as criterium of inappropriateness). Only U indications decreased over years (p = 0.003). Regarding CICCTA, 501/815 (61.5%) patients were categorized as I, 144/815 (17.7%) as II, 102/815 (12.5%) as III, 67/815 (8.2%) were INV and 1/815 (0.1%) were non-classified. Clinical referrals were CA in 495/786 (63.0%), GPs in 57/786 (7.3%) GP and OS in 234/786 (29.8%) [p < 0.01]. No statistically significant differences were observed in the appropriateness among different specialty physicians. Younger doctors have a lower chance to not meet A indication (OR 0.98 [CI 95% 0.96-0.99]; p = 0.003). CONCLUSION: Our study highlights the importance of a pre-radiological visit prior to CCTA, which prevented execution of 19.9% of inappropriate examinations. Age of prescribers had an impact on appropriateness, with younger doctors having a lower chance to not meet A indication.

Use of the new Lake Louise Criteria improves CMR detection of atypical forms of acute myocarditis.

The purpose of our study was to compare diagnostic performance of old and new Lake Louise Criteria (oLLC and nLLC) among different clinical presentations: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR). 102 patients with clinical suspicion of acute myocarditis underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. Protocol included cine-SSFP, T2-weighted STIR, T2 mapping, early and late gadolinium enhancement and T1 mapping acquired before and after gadolinium administration. The degree of agreement has been calculated with Cohen's K test. 42 patients also underwent endomyocardial biopsy (EMB). IL onset was present in 54/102 patients, CM in 28/102 and AR in 20/102. nLLC were positive in 58.3% of the patients, while oLLC in 37.9%, k = 0.57 (IC: 0.428-0.713). The degree of agreement between nLLC and oLLC was 0.49 (IC: 0.111-0.876) for AR onset (nLLC positive in 35% vs oLLC in 15%), 0.25 (IC: 0.035-0.459) for CM pattern (nLLC positive in 60.7% vs oLLC 17.9%) and 0.73 (IC: 0.543-0.912) for IL presentation (nLLC positive in 66.7% vs oLLC in 57.4%). Diagnostic accuracy was 75% for both nLLC and oLLC among IL onset, and 41.6% for oLLC vs 66.7% for nLLC, as regards CM clinical presentation. nLLC have improved diagnostic performance of CMR for the diagnosis of acute myocarditis, in particular for atypical clinical presentation.