Usefulness of Alcohol Septal Ablation in the Left Ventricular Outflow Tract Obstruction in Fabry Disease Cardiomyopathy

Fabry disease (FD) is an X-linked linked genetic disorder caused by ?-galactosidase A deficiency. The typical clinical manifestation left ventricular hypertrophy, often mimicking hypertrophic cardiomyopathy (HC). In contrast to sarcomeric HC, outflow tract obstruction (LVOTO) less frequent. We describe 6 male patients with genetically confirmed FD and symptomatic LVOTO. All of them underwent a transcatheter alcohol septal ablation immediate effect on the in all cases without any serious complications. median LVOT maximal pressure gradient was 85 (60 170) mm Hg. hemodynamic persisted during subsequent follow-up (ranging from months 16 years). Five reported substantial improvement. Four were receiving specific therapy before interventional procedure. conclusion, appears be effective treatment LVOTO comparable limited published experience surgical myectomy. Despite some important differences between HC recommendation for treating should similar. rare (X-linked) mutations gene encoding (AGALA). Deficient AGALA activity leads intra-lysosomal accumulation neutral glycosphingolipids, predominantly globotriaosylceramide, various organ systems. manifests, its classic variant, multiple involvement age gender-dependent manifestations. Several can cause atypical (late-onset) variants affecting single organ, most frequently heart. Cardiac consists mainly progressive ventricle (LV) scarring, heart failure, tachyarrhythmias, bradycardia, valvular disease. many cases, phenotype mimic (HC).1Linhart Palecek T Bultas J Ferguson JJ Hrudová Karetová D Zeman Ledvinová Poupetová H Elleder M Aschermann M. New insights cardiac structural changes Fabry's disease.Am Heart J. 2000; 139: 1101-1108Crossref PubMed Scopus (205) Google Scholar,2Linhart Kampmann C Zamorano JL Sunder-Plassmann G Beck Mehta Elliott PM European FOS InvestigatorsCardiac manifestations Anderson-Fabry disease: results international outcome survey.Eur 2007; 28: 1228-1235Crossref (235) Scholar Unlike relatively rare. Nevertheless, it present subset may unmasked exercise.3Calcagnino O'Mahony Coats Cardona Garcia Janagarajan K Hughes Murphy E Lachmann R PM. Exercise-induced disease.J Am Coll Cardiol. 2011; 58: 88-89Crossref (25) Because underlying pathophysiology different there concern whether established non-pharmacological treatments would FD. literature describes only small group who have undergone myectomy,4Meghji Z Nguyen Miranda WR Geske JB Schaff HV Peck DS Newman DB. Surgical myectomy relief dynamic Disease.Int 2019; 292: 91-94Abstract Full Text PDF (5) Scholar,5Cecchi F Iascone Maurizi N Pezzoli L Binaco I Biagini Fibbi ML Olivotto Pieruzzi Fruntelata Dorobantu Rapezzi Ferrazzi P. Intraoperative diagnosis obstructive undergoing myectomy.JAMA 2017; : 21147-21151Google or case including discussion our previous abstract data.6Raju B Roberts CS Sathyamoorthy Schiffman Swift McCullough PA. Ventricular due 2020; 132: 160-164Abstract (2) However, report successful (ASA) previously.7Magage S Linhart Vojacek Mates Popelová Tintera Goldman ME Desnick RJ. percutaneous transluminal myocardial markedly improved hypertrophy classically affected male.Echocardiography. 2005; 22: 333-339Crossref (22) Our aim assess feasibility effectiveness ASA Consecutive LVOTO, cohort 200 observed treated institution, included study. through assessment testing. carrying mutation unknown significance, histological evidence (i.e., endomyocardial biopsy). LV screened examination ASA, which that symptoms attributable despite maximum tolerated beta-blocker therapy. Electrocardiography, transthoracic echocardiography, exercise echocardiography also performed whom planned. following echocardiographic parameters used analysis: resting provoked mid-ventricular gradient, interventricular posterior wall thickness, diameter atrium as seen parasternal long-axis view, trans-mitral flow tissue doppler imaging mitral annulus. Exercise using dedicated semi-supine bicycle ergometer. peak taken at beginning recovery period. Percutaneous patients, procedure similar HC. reason why these twofold. First, center, high surgery risk their perioperative care more complex compared other candidates. Secondly, greater than usually reserved (midventricular obstruction, …) complete atrioventricular block (left bundle branch block). applying amounts 96% (1 2 mL) proximal branch, guided echocardiography. temporary pacemaker lead inserted into right (except where automatic implantable defibrillator already present). Written informed consent obtained patients; systematic previously approved local ethics committee under separate written consent. received regular intervals, measured rest Valsalva maneuver. Due number cohort, statistical descriptions. No further analysis performed. From May 2001 August 2019, unrelated institution. time intervention 52 (41 54) years. characteristics are shown Table 1. presence pathogenic cases. An extra-cardiac 5 ASA. enzyme replacement fifth patient, initiated same sixth patient started years after (our first described not available Czech Republic time). Two had cardioverter-defibrillator (one arrest, second primary sudden death prevention). highly - NYHA class III. pharmacologic (beta-blockers). significant thickness 21 (18 25) mm, 48 50) mm. Diastolic function impaired 4 we relaxation pattern, pseudo-normal filling pattern. Electrocardiography showed sinus rhythm, normal PQ interval slightly prolonged QRS duration 120 (110 138) ms. Nobody block.Table 1The (in chronological order date procedure)Pt. No.Age (years)Age (years)Gene mutationAgalsidase (age start [years])Max. IVS (mm)ICDExtracardiac manifestationNYHA beforeClass after14953c.[901 C>T]- (56)21-Neurologic, PU, cornea vercilata, angiokeratomaIII.II.24851c.[973 G>A]+ (49)25+RRT, neurologic (TIA)III.II.34852c.[801+ 48T>G]+ (49)18-Cornea verticilataIII.I.43641c.[902 (37)21+Neurologic, PUIII.III.55354c.[801+ 48T>G]- (54)21--III.I.63046c.[950 T>C]+ (30)19-RRT, acroparesthesiaIII.II.ASA = ablation; intervenricular septum; ICD cardioverter defibrillator; PU proteinuria; RRT renal therapy; TIA transient ischemic attack; York Association classification failure. Open table new tab standard technique, Specifically, no block, tamponade, stroke, bleeding acute failure observed. amount applied 1.5 mL (1.2 2.0). Invasive measurements (peak-to-peak invasive gradient) positive (Figure 1). pacing ICD) removed hours. length post-procedural in-hospital stay (3 7) days. subjective symptom discharge. demonstrated care. decline presented Figure 1 (for 6-month 1-year available). improvement (of least class) patients. Only exertional dyspnea follow-up. safety subjects, this shows excellent short-term mid-term relative reduction. but 1, led Moreover, periprocedural complications (e.g., AV bleeding, etc.) method has long history experienced centers.8Geske Driver CN Yogeswaran V Ommen SR HV. Comparison expected outcomes cardiomyopathy.Am 221: 159-164Crossref (7) selected been unequivocal reduction relieve symptoms, potentially prognoses.9Lemor Villablanca PA Hosseini Dehkordi SH Mand Hernandez GA Jain Blumer VL Lee Eng Guerrero Wang DD Palacios O'Neill W. ?65 versus >65 years.Am 127: 128-134Abstract (6) identical characterized diffuse marked papillary muscle infiltration. insertion leaflet anatomy HC.1Linhart Given nature character FD, might seem better choice treatment. multiorgan represent high-risk surgery. Therefore, appropriate coronary pathology obstruction. pathophysiological basis (enzyme – ERT). theory, ERT beneficial LVOTO.10Germain DP Falissard Fomin VV Hilz MJ Jovanovic Kantola Mignani Namdar Nowak Oliveira JP Pieroni Viana-Baptista Wanner Spada review panel experts.Mol Genet Metab Rep. 19100454Crossref (61) mass induced modest. well Mayo Clinic, treatment.4Meghji Thus, unlikely prevent development pre-existing even likely eliminate Of note achieved almost subjects. multifactorial absence LVOTO.11Coats CJ Parisi Ramos Dawnay RH Role serum N-terminal pro-brain natriuretic peptide measurement 2013; 111: 111-117Abstract (46) It seems mostly filling. pulmonary advanced FD.12Magage Lubanda JC Susa Dobrovolný Hrebícek Germain A. Natural respiratory Inherit Dis. 30: 790-799Crossref (43) terms mortality clinic.4Meghji main limitation study sample size. disease, reports similarly proof concept, properly feasible Another follow-up, evaluated show experiences David Zemánek: Conceptualization, Investigation, Writing Original Draft, Josef Marek Review & Editing, Gabriela Dostálová Sudheera Magage Lenka Roblová Tomáš Kovárník Aleš Supervision, Editing authors conflicts interest disclose.