Publications by authors named "Ilaria Rigato"

45 Publications

'Hot phase' clinical presentation in arrhythmogenic cardiomyopathy.

Europace 2020 Dec 13. Epub 2020 Dec 13.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, 35121 Padua, Italy.

Aims: The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries ('hot phase').

Methods And Results: We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the 'hot phase'.

Conclusion: 'Hot phase' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.
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http://dx.doi.org/10.1093/europace/euaa343DOI Listing
December 2020

Arrhythmogenic Cardiomyopathy.

Eur Heart J 2020 12;41(47):4457-4462

Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua Medical School, Padua, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehaa719DOI Listing
December 2020

Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria.

Int J Cardiol 2020 11 16;319:106-114. Epub 2020 Jun 16.

Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Italy.

The original designation of "Arrhythmogenic right ventricular (dysplasia/) cardiomyopathy"(ARVC) was used by the scientists who first discovered the disease, in the pre-genetic and pre-cardiac magnetic resonance era, to describe a new heart muscle disease predominantly affecting the right ventricle, whose cardinal clinical manifestation was the occurrence of malignant ventricular arrhythmias. Subsequently, autopsy investigations, genotype-phenotype correlations studies and the increasing use of contrast-enhancement cardiac magnetic resonance showed that the fibro-fatty replacement of the myocardium represents the distinctive phenotypic feature of the disease that affects the myocardium of both ventricles, with left ventricular involvement which may parallel or exceed the severity of right ventricular involvement. This has led to the new designation of "Arrhythmogenic Cardiomyopathy" (ACM), that represents the evolution of the original term of ARVC. The present International Expert Consensus document proposes an upgrade of the criteria for diagnosis of the entire spectrum of the phenotypic variants of ACM. The proposed "Padua criteria" derive from the diagnostic approach to ACM, which has been developed over 30 years by the multidisciplinary team of basic researchers and clinical cardiologists of the Medical School of the University of Padua. The Padua criteria are a working framework to improve the diagnosis of ACM by introducing new diagnostic criteria regarding tissue characterization findings by contrast-enhanced cardiac magnetic resonance, depolarization/repolarization ECG abnormalities and ventricular arrhythmia features for diagnosis of the left ventricular phenotype. The proposed diagnostic criteria need to be further validated by future clinical studies in large cohorts of patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.005DOI Listing
November 2020

Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy.

J Am Heart Assoc 2020 03 2;9(5):e014628. Epub 2020 Mar 2.

Department of Cardio-Thoraco-Vascular Sciences and Public Health University of Padua Italy.

Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC-LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34 years) and 153 DCM patients (median age 51 years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty-eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV-LGE in isolation in 17 (29%). Compared with DCM, the ARVC-LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T-wave inversion in the inferolateral leads and major ventricular arrhythmias. LV-LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV-LGE (25% versus 13% of LV mass; <0.01), mostly localized in the subepicardial LV wall layers. An LV-LGE ≥20% had a 100% specificity for diagnosis of ARVC-LV phenotype. An inverse correlation between LV ejection fraction and LV-LGE extent was found in the ARVC-LV phenotype (=-0.63; <0.01), but not in DCM (=-0.01; =0.94). Conclusions LV involvement in ARVC is common and characterized by clinical and cardiac magnetic resonance features which differ from those seen in DCM. The most distinctive feature of ARVC-LV phenotype is the large amount of LV-LGE/fibrosis, which impacts directly and negatively on the LV systolic function.
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http://dx.doi.org/10.1161/JAHA.119.014628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335583PMC
March 2020

Subcutaneous implantable cardioverter defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy: Results from an Italian multicenter registry.

Int J Cardiol 2019 04 12;280:74-79. Epub 2019 Jan 12.

Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy. Electronic address:

Background: Despite expanding indication of the subcutaneous implantable cardioverter defibrillator (S-ICD) in clinical practice, limited data exists on safety and efficacy of S-ICD in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. The aim of this multicenter study was to evaluate the safety and efficacy of S-ICD in ARVC patients.

Methods: The study population included 44 consecutive patients with definite ARVC diagnosis according to the 2010 ITF criteria (57% male, mean age 37 ± 17 years [range 10-75 years]) who received an S-ICD. Eighteen (41%) patients were implanted for secondary prevention.

Results: At implant, all inducible patients (34/44) had conversion of ventricular fibrillation at 65 J. No early complications occurred. During a median follow-up of 12 months (7-19), 3 (6.8%) patients experienced complications requiring surgical revision. No local or systemic device-related infections were observed. Six patients (14%) received a total of 61 appropriate and successful shocks on ventricular arrhythmias. Six (14%) patients experienced 8 inappropriate shocks for oversensing of cardiac signal (4 cases) and non-cardiac signal (4 cases) with one patient requiring device explantation. No patients had the device explanted due to the need for antitachycardia pacing.

Conclusions: The study shows that S-ICD provides safe and effective therapy for termination of both induced and spontaneous malignant ventricular tachyarrhythmias with high energy shocks in ARVC patients, but the risk of inappropriate shocks and complications needing surgical revision should be considered.
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http://dx.doi.org/10.1016/j.ijcard.2019.01.041DOI Listing
April 2019

Relationship Between Electrocardiographic Findings and Cardiac Magnetic Resonance Phenotypes in Arrhythmogenic Cardiomyopathy.

J Am Heart Assoc 2018 11;7(22):e009855

1 Department of Cardiac, Thoracic and Vascular Sciences University of Padova Italy.

Background The new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated the relationship between electrocardiographic findings and contrast-enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy. Methods and Results We studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast-enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T-wave inversion across a 12-lead ECG and increasing values of median right ventricular ( RV ) end-diastolic volume ( P<0.001) and decreasing values of RV ejection fraction ( P<0.001). The extent of T-wave inversion to lateral leads predicted a more severe RV dilatation rather than a left ventricular involvement because of the leftward displacement of the dilated RV , as evidenced by contrast-enhanced cardiac magnetic resonance. A terminal activation delay of >55 ms in the right precordial leads (V1-V3) was associated with higher RV volume ( P=0.014) and lower RV ejection fraction ( P=0.053). Low QRS voltages in limb leads predicted the presence ( P=0.004) and amount ( P<0.001) of left ventricular late gadolinium enhancement. Conclusions The study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome.
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http://dx.doi.org/10.1161/JAHA.118.009855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404435PMC
November 2018

A targeted next-generation gene panel reveals a novel heterozygous nonsense variant in the TP63 gene in patients with arrhythmogenic cardiomyopathy.

Heart Rhythm 2019 05 17;16(5):773-780. Epub 2018 Nov 17.

Department of Biology, University of Padua, Padua, Italy.

Background: Arrhythmogenic cardiomyopathy (ACM) is associated with arrhythmias and risk of sudden death. Mutations in genes encoding proteins of cardiac intercalated discs account for ∼60% of ACM cases, but the remaining 40% is still genetically elusive.

Objective: The purpose of this study was to identify the underlying genetic cause in probands with ACM.

Methods: DNA samples from 40 probands with ACM, negative for mutations in the 3 major ACM genes-DSP, PKP2, and DSG2, were screened by using a targeted gene panel consisting of 15 known ACM genes and 53 candidate genes.

Results: About half of patients were found to carry rare variant(s) predicted to be damaging; specifically, 9 (22.5%) showed ≥1 variants in genes associated with ACM and/or with other inherited heart diseases and 10 (25%) showed variants in candidate genes. Among the latter, we focused on 2 novel variants in TP63 and PPP1R13L candidate genes (c.796C>T, p.(R266*) and c.1858G>C, p.(A620P), respectively). The encoded proteins p63 and inhibitor of apoptosis stimulating p53 protein are known to be interacting partners. Inhibitor of apoptosis stimulating p53 protein is a shuttling multifunctional protein: in the nucleus it is critical for inhibiting p63 function, whereas in the cytoplasm it regulates desmosome integrity. According to the American College of Medical Genetics and Genomics guidelines, the variant in TP63 has been scored as likely pathogenic and the variant in PPP1R13L as a variant of uncertain significance. Importantly, the mutant TP63 allele leads to nonsense-mediated messenger RNA decay, causing haploinsufficiency.

Conclusion: Our findings identify TP63 as a putative novel disease gene for ACM, while the possible involvement of PPP1R13L remains to be determined.
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http://dx.doi.org/10.1016/j.hrthm.2018.11.015DOI Listing
May 2019

Whole-Exome Sequencing Identifies Pathogenic Variants in TJP1 Gene Associated With Arrhythmogenic Cardiomyopathy.

Circ Genom Precis Med 2018 10;11(10):e002123

Departments of Biology (M.D.B., G.P., M.C., A.L., G.V., A.R.).

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by progressive fibro-fatty myocardial replacement, ventricular arrhythmia, heart failure, and sudden death. Causative mutations can be identified in 60% of patients, and most of them are found in genes encoding mechanical junction proteins of the intercalated disk.

Methods: Whole-exome sequencing was performed on the proband of an ACM family. Sanger sequencing was used to screen for mutations the tight junction protein 1 ( TJP1) gene in unrelated patients. Predictions of local structure content and molecular dynamics simulations were performed to investigate the structural impact of the variants.

Results: A novel c.2006A>G p.(Y669C) variant in TJP1 gene was identified by whole-exome sequencing in a patient with ACM. TJP1 encodes zonula occludens 1, an intercalated disk protein interacting with proteins of gap junctions and area composita. Additional rare TJP1 variants have been identified in 1 of 40 Italian probands (c.793C>T p.(R265W)) with arrhythmogenic right ventricular cardiomyopathy and in 2 of 43 Dutch/German patients (c. 986C>T, p.(S329L) and c.1079A>T, p.(D360V)) with dilated cardiomyopathy and recurrent ventricular tachycardia. The p.(D360V) variant was identified in a proband also carrying the p.(I156N) pathogenic variant in DSP. All 4 TJP1 variants are predicted to be deleterious and affect highly conserved amino acids, either at the GUK (guanylate kinase)-like domain (p.(Y669C)) or at the disordered region of the protein between the PDZ2 and PDZ3 domains (p.(R265W), p.(S329L), and p.(D360V)). The local unfolding induced by the former promotes structural rearrangements of the GUK domain, whereas the others are predicted to impair the function of the disordered region. Furthermore, rare variants in TJP1 are statistically enriched in patients with ACM relative to controls.

Conclusions: We provide here the first evidence linking likely pathogenic TJP1 variants to ACM. Prevalence and pathogenic mechanism of TJP1-mediated ACM remain to be determined.
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http://dx.doi.org/10.1161/CIRCGEN.118.002123DOI Listing
October 2018

Predictive value of exercise testing in athletes with ventricular ectopy evaluated by cardiac magnetic resonance.

Heart Rhythm 2019 02 30;16(2):239-248. Epub 2018 Aug 30.

Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy. Electronic address:

Background: Exercise-induced ventricular arrhythmias (EIVA) in young athletes raise the suspicion of an underlying heart disease at risk of sudden death.

Objective: We aimed to assess the prevalence and determinants of abnormal cardiac magnetic resonance (CMR) findings in athletes referred for EIVA vs non-EIVA with negative or inconclusive echocardiography.

Methods: We performed CMR in a consecutive series of athletes aged 15-50 years referred for frequent (>500 per day) or repetitive premature ventricular beats. Clinical and CMR findings were compared between athletes with EIVA and those with non-EIVA, and predictors of abnormal CMR were assessed.

Results: We included 36 athletes with EIVA (median age 25 years; 27 (75%) males) and 24 with non-EIVA (median age 17 years; 18 (75%) males). CMR revealed cardiac abnormalities in 20 athletes with EIVA (56%) and in 5 with non-EIVA (21%) (P = .004). In particular, left ventricular late gadolinium enhancement was identified in 17 athletes with EIVA (47%) and in 3 with non-EIVA (13%) (P = .006), mostly with a nonischemic pattern. Predictors of abnormal CMR were T-wave inversion on electrocardiography (ECG) (odds ratio [OR] 5.2; 95% confidence interval [CI] 1.0-27.1; P = .05), complex ventricular arrhythmias on 24-hour ambulatory ECG monitoring (OR 4.5; 95% CI 1.1-18.7; P = .04), and complex EIVA with a right bundle branch block or polymorphic morphology on exercise testing (OR 5.3; 95% CI 1.4-19.4; P = .01).

Conclusion: Pathological myocardial substrates on CMR were observed significantly more often in athletes with EIVA than in those with non-EIVA. Repolarization abnormalities on baseline ECG and complex EIVA with a right bundle branch block or polymorphic morphology identified the subgroup of athletes with the highest probability of CMR abnormalities.
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http://dx.doi.org/10.1016/j.hrthm.2018.08.029DOI Listing
February 2019

Large Genomic Rearrangements of Desmosomal Genes in Italian Arrhythmogenic Cardiomyopathy Patients.

Circ Arrhythm Electrophysiol 2017 Oct;10(10)

From the Departments of Cardiac, Thoracic, and Vascular Sciences (K.P., E.L., I.R., R.C., M.P.M., M.C., S.R., S.I., L.D., D.C., G. T., C.B., B.B.) and Medicine (D.R.), University of Padua, Italy; Department of Biology, University of Padua, Italy (M.D.B., M.C., G.P., A.R., A.L., G.O.); University Medical Center Groningen, University of Groningen, The Netherlands (J.J.); Cardiology Division, Casa di Cura Pederzoli, Peschiera del Garda, Italy (P.D.); and Department of Clinical Genetics, University of Amsterdam, The Netherlands (J.P.V.T.).

Background: Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disease associated with point mutations in genes encoding for cardiac desmosome proteins. Conventional mutation screening is positive in ≈50% of probands. Copy number variations (CNVs) have recently been linked to AC pointing to the need to determine the prevalence of CNVs in desmosomal genes and to evaluate disease penetrance by cosegregation analysis in family members.

Methods And Results: A total of 160 AC genotype-negative probands for 5 AC desmosomal genes by conventional mutation screening underwent multiplex ligation-dependent probe amplification. Nine heterozygous CNVs were identified in 11 (6.9%) of the 160 probands. Five carried a deletion of the entire plakophilin-2 () gene, 2 a deletion of only exon 4, 1 a deletion of the exons 6 to 11, 1 a duplication of 5' untranslated region till exon 1, 1 the desmocollin-2 () duplication of exons 7 to 9, and 1 a large deletion of chromosome 18 comprising both and genes. All probands were affected by moderate-severe forms of the disease, whereas 10 (32%) of the 31 family members carrying one of these deletions fulfilled the diagnostic criteria.

Conclusions: Genomic rearrangements were detected in ≈7% of AC probands negative for pathogenic point mutations in desmosomal genes, highlighting the potential of CNVs analysis to substantially increase the diagnostic yield of genetic testing. Genotype-phenotype correlation demonstrated the presence of the disease in about one third of family members carrying the CNV, underlying the role of other factors in the development and progression of the disease.
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http://dx.doi.org/10.1161/CIRCEP.117.005324DOI Listing
October 2017

Co-inheritance of mutations associated with arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy.

Eur J Hum Genet 2017 10 12;25(10):1165-1169. Epub 2017 Jul 12.

Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.

Arrhythmogenic cardiomyopathy (ACM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically distinct disorders of the myocardium. Here we describe for the first time co-inheritance of mutations in genes associated with ACM or HCM in two families with recurrence of both cardiomyopathies. Among the double heterozygotes for mutations in desmoplakin (DSP) and myosin binding protein C (MYBPC3) genes identified in Family A, two were diagnosed with ACM and two with HCM. In Family B, one patient was identified to carry mutations in α-T-catenin (CTTNA3) and β-myosin (MYH7) genes, but he does not fulfill the current diagnostic criteria neither for ACM nor for HCM. Interestingly, the double heterozygotes showed a variable clinical expression of both cardiomyopathies and they do not exhibit a more severe phenotype than family members carrying only one of the two mutations.
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http://dx.doi.org/10.1038/ejhg.2017.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602010PMC
October 2017

Electrocardiographic differentiation of idiopathic right ventricular outflow tract ectopy from early arrhythmogenic right ventricular cardiomyopathy.

Europace 2017 Apr;19(4):622-628

Institute of Cardiovascular Science, University College of London, London, UK.

Aims: The differentiation between idiopathic right ventricular outflow tract (RVOT) arrhythmias and early arrhythmogenic right ventricular cardiomyopathy (ARVC) can be challenging. We aimed to assess whether QRS morphological features and coupling interval of ventricular ectopic beats (VEBs) can improve differentiation between the two conditions.

Methods And Results: Twenty desmosomal-gene mutation carriers (13 females, mean age 43 years) with no or mild ARVC phenotypic expression and 33 age- and sex-matched subjects with idiopathic RVOT arrhythmias were studied. All patients exhibited isolated monomorphic VEBs with left bundle branch block/inferior axis morphology. The predictive value of ectopic QRS morphology and coupling interval was evaluated. Five ectopic QRS features were significantly more common in desmosomal-gene mutation carriers than in idiopathic RVOT-ventricular arrhythmia patients: maximal QRS duration >160 ms (60 vs. 27%, P = 0.02), intrinsicoid deflection time >80 ms (65 vs. 24%, P = 0.01), initial QRS slurring (40 vs. 12%, P = 0.04), QS pattern in lead V1 (90 vs. 36%, P < 0.001), and QRS axis >90° in limb leads (60 vs. 24%, P = 0.01). In the multivariate analysis, intrinsicoid deflection time >80 ms [odds ratio (OR) = 9.9], QS pattern in lead V1 (OR = 28), and QRS axis >90° (OR = 5.7) remained independent predictors of early ARVC. The coupling interval did not differ between the two groups.

Conclusions: In patients with RVOT VEBs and no major electrocardiographic or echocardiographic abnormalities, the ectopic QRS morphology aids in the differential diagnosis between idiopathic RVOT arrhythmias and early ARVC.
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http://dx.doi.org/10.1093/europace/euw018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400079PMC
April 2017

Morphofunctional Abnormalities of Mitral Annulus and Arrhythmic Mitral Valve Prolapse.

Circ Cardiovasc Imaging 2016 08;9(8):e005030

From the Department of Cardiac, Thoracic, and Vascular Sciences (M.P.M., C.B., M.D.L., S.R., A.C., I.R., F.M., K.P., L.C., E.B., A.C.F., B.B., D.C., G.T., S.I.), Department of Medicine (B.G.), and Department of Radiology (C.L.), Azienda Ospedaliera-University of Padua Medical School, Italy.

Background: Arrhythmic mitral valve prolapse (MVP) is characterized by myxomatous leaflets and left ventricular (LV) fibrosis of papillary muscles and inferobasal wall. We searched for morphofunctional abnormalities of the mitral valve that could explain a regional mechanical myocardial stretch.

Methods And Results: Thirty-six (27 female patients; median age: 44 years) arrhythmic MVP patients with LV late gadolinium enhancement on cardiac magnetic resonance and no or trivial mitral regurgitation, and 16 (6 female patients; median age: 40 years) MVP patients without LV late gadolinium enhancement were investigated by morphofunctional cardiac magnetic resonance. Mitral annulus disjunction (median: 4.8 versus 1.8 mm; P<0.001), end-systolic mitral annular diameters (median: 41.2 versus 31.5; P=0.004) and end-diastolic mitral annular diameters (median: 35.5 versus 31.5; P=0.042), prevalence of posterior systolic curling (34 [94%] versus 3 [19%]; P<0.001), and basal to mid LV wall thickness ratio >1.5 (22 [61%] versus 4 [25%]; P=0.016) were higher in MVP patients with late gadolinium enhancement than in those without. A linear correlation was found between mitral annulus disjunction and curling (R=0.85). A higher prevalence of auscultatory midsystolic click (26 [72%] versus 6 [38%]; P=0.018) was also noted. Histology of the mitral annulus showed a longer mitral annulus disjunction in 50 sudden death patients with MVP and LV fibrosis than in 20 patients without MVP (median: 3 versus 1.5 mm; P<0.001).

Conclusions: Mitral annulus disjunction is a constant feature of arrhythmic MVP with LV fibrosis. The excessive mobility of the leaflets caused by posterior systolic curling accounts for a mechanical stretch of the inferobasal wall and papillary muscles, eventually leading to myocardial hypertrophy and scarring. These mitral annulus abnormalities, together with auscultatory midsystolic click, may identify MVP patients who would need arrhythmic risk stratification.
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http://dx.doi.org/10.1161/CIRCIMAGING.116.005030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991345PMC
August 2016

Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes.

Circ Arrhythm Electrophysiol 2016 07;9(7)

From the Department of Cardiac, Thoracic, and Vascular Sciences (A.Z., M.P.M., I.R., M.D.L., A.S., A.N., K.P., F.M., S.R., C.B., B.B., S.I., G.T., D.C.) and Division of Radiology, Department of Medicine (B.G.), University of Padova, Padova, Italy; Department of Radiology, Azienda Ospedaliera di Padova, Padova, Italy (G.D.C.); Center for Sports Medicine, Treviso, Italy (P.S.); Unidad de Cardiologica del Deporte, Hospital Universitario Quiron, Madrid, Spain (L.S.); U.O. Cardiologia, Ospedale B.Ramazzini, Carpi (MO), Italy (G.P., E.D.M.); Center for Sports Medicine, CONI, Rome, Italy (A.P.); and Center for Sports Medicine, Padova, Italy (M.S.).

Background: The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated.

Methods And Results: We compared 35 athletes (80% men, age: 14-48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls.

Conclusions: Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography.
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http://dx.doi.org/10.1161/CIRCEP.116.004229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956679PMC
July 2016

Management of arrhythmogenic right ventricular cardiomyopathy.

Minerva Med 2016 Aug 17;107(4):194-216. Epub 2016 May 17.

Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, Medical School, University of Padua, Padua, Italy -

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder, predisposing to sudden cardiac death (SCD), particularly in young patients and athletes. Pathological features include loss of myocytes and fibrofatty replacement of right ventricular myocardium; a biventricular involvement is often observed. The diagnosis of ARVC (prevalence 1:5.000 in the general population) does not rely on a single gold standard test but is achieved using a scoring system, proposed in 2010 by an International Task Force, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations. The main goal of treatment is the prevention of SCD. Implantable cardioverter defibrillator (ICD) is the only proven "lifesaving" therapy; however, it is associated with a significant morbidity due to device-related complications and inappropriate ICD interventions. Other treatment options such as life style changes, antiarrhythmic drugs, beta-blockers and catheter ablation may reduce the arrhythmic burden and alleviate symptoms, without evident impact on prevention of SCD. Selection of patient candidates to ICD implantation is the most challenging issue in the clinical management of ARVC. This article reviews the current perspective on management of ARVC, focusing on clinical manifestations, diagnostic criteria, risk stratification and therapeutic strategies of affected patients.
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August 2016

Arrhythmogenic Right Ventricular Cardiomyopathy: Risk Stratification and Indications for Defibrillator Therapy.

Curr Cardiol Rep 2016 06;18(6):57

Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined disease which predisposes to life-threatening ventricular arrhythmias. The main goal of ARVC therapy is prevention of sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) is the most effective therapy for interruption of potentially lethal ventricular tachyarrhythmias. Despite its life-saving potential, ICD implantation is associated with a high rate of complications and significant impact on quality of life. Accurate risk stratification is needed to identify individuals who most benefit from the therapy. While there is general agreement that patients with a history of cardiac arrest or hemodynamically unstable ventricular tachycardia are at high risk of SCD and needs an ICD, indications for primary prevention remain a matter of debate. The article reviews the available scientific evidence and guidelines that may help to stratify the arrhythmic risk of ARVC patients and guide ICD implantation. Other therapeutic strategies, either alternative or additional to ICD, will be also addressed.
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http://dx.doi.org/10.1007/s11886-016-0734-9DOI Listing
June 2016

Arrhythmogenic cardiomyopathy.

Orphanet J Rare Dis 2016 Apr 2;11:33. Epub 2016 Apr 2.

Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.

Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias and pathologically by an acquired and progressive dystrophy of the ventricular myocardium with fibro-fatty replacement. Due to an estimated prevalence of 1:2000-1:5000, AC is listed among rare diseases. A familial background consistent with an autosomal-dominant trait of inheritance is present in most of AC patients; recessive variants have also been reported, either or not associated with palmoplantar keratoderma and woolly hair. AC-causing genes mostly encode major components of the cardiac desmosome and up to 50% of AC probands harbor mutations in one of them. Mutations in non-desmosomal genes have been also described in a minority of AC patients, predisposing to the same or an overlapping disease phenotype. Compound/digenic heterozygosity was identified in up to 25% of AC-causing desmosomal gene mutation carriers, in part explaining the phenotypic variability. Abnormal trafficking of intercellular proteins to the intercalated discs of cardiomyocytes and Wnt/beta catenin and Hippo signaling pathways have been implicated in disease pathogenesis.AC is a major cause of sudden death in the young and in athletes. The clinical picture may include a sub-clinical phase; an overt electrical disorder; and right ventricular or biventricular pump failure. Ventricular fibrillation can occur at any stage. Genotype-phenotype correlation studies led to identify biventricular and dominant left ventricular variants, thus supporting the use of the broader term AC.Since there is no "gold standard" to reach the diagnosis of AC, multiple categories of diagnostic information have been combined and the criteria recently updated, to improve diagnostic sensitivity while maintaining specificity. Among diagnostic tools, contrast enhanced cardiac magnetic resonance is playing a major role in detecting left dominant forms of AC, even preceding morpho-functional abnormalities. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, sarcoidosis, dilated cardiomyopathy, right ventricular infarction, congenital heart diseases with right ventricular overload and athlete heart. A positive genetic test in the affected AC proband allows early identification of asymptomatic carriers by cascade genetic screening of family members. Risk stratification remains a major clinical challenge and antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator are the currently available therapeutic tools. Sport disqualification is life-saving, since effort is a major trigger not only of electrical instability but also of disease onset and progression. We review the current knowledge of this rare cardiomyopathy, suggesting a flowchart for primary care clinicians and geneticists.
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http://dx.doi.org/10.1186/s13023-016-0407-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818879PMC
April 2016

Relationship Between Arrhythmogenic Right Ventricular Cardiomyopathy and Brugada Syndrome: New Insights From Molecular Biology and Clinical Implications.

Circ Arrhythm Electrophysiol 2016 Apr;9(4):e003631

From the Departments of Cardiac, Thoracic, and Vascular Sciences (D.C., A.Z., I.R., B.B.) and Biomedical Sciences (M.M.), University of Padua, Padova, Italy; and The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.C., M.D.).

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http://dx.doi.org/10.1161/CIRCEP.115.003631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800833PMC
April 2016

Homozygous Desmocollin-2 Mutations and Arrhythmogenic Cardiomyopathy.

Am J Cardiol 2015 Oct 28;116(8):1245-51. Epub 2015 Jul 28.

Department of Biology, University of Padua, Padua, Italy. Electronic address:

Dominant mutations in desmocollin-2 (DSC2) gene cause arrhythmogenic cardiomyopathy (ACM), a progressive heart muscle disease characterized by ventricular tachyarrhythmias, heart failure, and risk of juvenile sudden death. Recessive mutations are rare and are associated with a cardiac or cardiocutaneous phenotype. Here, we evaluated the impact of a homozygous founder DSC2 mutation on clinical expression of ACM. An exon-by-exon analysis of the DSC2 coding region was performed in 94 ACM index patients. The c.536A>G (p.D179G) mutation was identified in 5 patients (5.3%), 4 of which resulted to be homozygous carriers. The 5 subjects shared a conserved haplotype, strongly indicating a common founder. Genetic and clinical investigation of probands' families revealed that p.D179G homozygous carriers displayed severe forms of biventricular cardiomyopathy without hair or skin abnormalities. The only heterozygous proband, who carried an additional variant of unknown significance in αT-catenin gene, showed a mild form of ACM without left ventricular involvement. All heterozygous family members were clinically asymptomatic. In conclusion, this is the first homozygous founder mutation in DSC2 gene identified among Italian ACM probands. Our findings provide further evidence of the occurrence of recessive DSC2 mutations in patients with ACM predominantly presenting with biventricular forms of the disease.
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http://dx.doi.org/10.1016/j.amjcard.2015.07.037DOI Listing
October 2015

Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death.

Circulation 2015 Aug 9;132(7):556-66. Epub 2015 Jul 9.

From Departments of Cardiac, Thoracic, and Vascular Sciences (C.B., M.P.M., S.R., M.D.L., A.C., A.C.F., I.R. F.M., K.P., E.B., L.C., B.B., D.C., G.T., S.I.) and Radiology (B.G.), Azienda Ospedaliera-University of Padua Medical School, Padua, Italy.

Background: Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular electric instability remains elusive.

Methods And Results: The cardiac pathology registry of 650 young adults (≤40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re-examined. Forty-three patients with MVP (26 females; age range, 19-40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28-43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects (P<0.001), with a regional distribution overlapping the histopathology findings in SCD cases.

Conclusions: MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016291DOI Listing
August 2015

Phenotypic expression is a prerequisite for malignant arrhythmic events and sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy.

Europace 2016 Jul 2;18(7):1086-94. Epub 2015 Jul 2.

Inherited Arrhythmogenic Cardiomyopathy Unit, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Via N. Giustiniani 2, Padua 35121, Italy

Aims: Whether a desmosomal (DS)-gene defect may in itself induce life-threatening ventricular arrhythmias regardless of phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) is still debated. This prospective study evaluated the long-term outcome of DS-gene mutation carriers in relation to the ARVC phenotypic expression.

Methods And Results: The study population included 116 DS-gene mutation carriers [49% males; median age 33 years (16-48 years)] without prior sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The incidence of the arrhythmic endpoint, including sudden cardiac death (SCD), aborted SCD, sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) intervention was evaluated prospectively and stratified by the presence of ARVC phenotype and risk factors (syncope, ventricular dysfunction, and non-sustained VT). At enrolment, 40 of 116 (34%) subjects fulfilled the criteria for definite ARVC while the remaining were either borderline or phenotype negatives. During a median follow-up of 8.5 (5-12) years, 10 patients (9%) had arrhythmic events (0.9%/year). The event rate was 2.3%/year among patients with definite ARVC and 0.2%/year among borderline or phenotype negative patients (P = 0.002). In patients with definite ARVC, the incidence of arrhythmias was higher in those with ≥1 risk factors (4.1%/year) than in those with no risk factors (0.4%/year, P = 0.02). Mortality was 0.2%/year (1 heart failure death and 1 SCD).

Conclusions: The ARVC phenotypic expression is a prerequisite for the occurrence of life-threatening arrhythmias in DS-gene mutation carriers. The vast majority of malignant arrhythmic events occurred in patients with an overt disease phenotype and major risk factors suggesting that this subgroup most benefits from ICD therapy.
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http://dx.doi.org/10.1093/europace/euv205DOI Listing
July 2016

Is Internet use associated with anxiety in patients with and at risk for cardiomyopathy?

Am Heart J 2015 Jul 9;170(1):87-95, 95.e1-4. Epub 2015 Apr 9.

Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. Electronic address:

Objective: The aim of the study was to determine the relation between online health information seeking behavior and anxiety level among a sample of patients with manifested cardiomyopathy or at risk for cardiomyopathy.

Methods: The research is a cross-sectional study conducted among 104 patients with cardiomyopathy diagnosis and patients at risk for cardiomyopathy. Patients completed 3 different questionnaires: Use of Internet Health Information questionnaire about the use of Internet, Short Form SF-12 items questionnaire on quality of life, and State-Trait Anxiety Inventory measuring general anxiety levels.

Results: Forty-eight patients had a diagnosis of primary or secondary cardiomyopathy, and 56 patients, with conditions predisposing to cardiomyopathy. Eighty-five percent of the considered population is surfing the Internet to obtain nonspecific information about health in general, and the 65% use it to look specifically for heart disease. For both groups of patients with cardiomyopathy and at risk for cardiomyopathy, online health information seeking behavior is associated with substantially lower state anxiety levels (P = .041).

Conclusion: Web use, as a source of health information, has been shown to be associated with anxiety reduction in patients with or at risk for cardiomyopathy, suggesting that Internet technology can be a useful instrument due to its informational power and its potentially therapeutic value.
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http://dx.doi.org/10.1016/j.ahj.2015.02.024DOI Listing
July 2015

Pharmacotherapy and other therapeutic modalities for managing Arrhythmogenic Right Ventricular Cardiomyopathy.

Cardiovasc Drugs Ther 2015 Apr;29(2):171-7

Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a genetically determined rare cardiomyopathy (1 in 5000 to 1 in 2000 in the general population), which can lead to ventricular arrhythmias and sudden death (SD). The classic form of the disease has a predilection for the right ventricle (RV), but recognition of left-dominant and biventricular variants led to the broader term "Arrhythmogenic Cardiomyopathy". The disease affects men more frequently than women and becomes clinically overt usually from the second to the fourth decade of life. Treatment consists of restriction of physical exercise, antiarrhythmic drugs, catheter ablation and ICD implantation. These treatments have the potential to change the natural history of the disease by protecting against SD and offering a good-quality and nearly normal life-expectancy. Antiarrhythmic drugs play an important role in terms of reduction of both the number and the complexity of arrhythmias, but they do not reduce the risk of SD. The results of catheter ablation are poor because of the high rate of VT recurrence. ICD should be reserved to selected patients after an accurate risk stratification. The clinical challenge is to improve risk stratification for better identification of those patients who most benefit from the above therapies. Unfortunately, a curative therapy is not yet available.
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http://dx.doi.org/10.1007/s10557-015-6583-8DOI Listing
April 2015

Differential diagnosis between early repolarization of athlete's heart and coved-type Brugada electrocardiogram.

Am J Cardiol 2015 Feb 29;115(4):529-32. Epub 2014 Nov 29.

Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. Electronic address:

Early repolarization (ER) is typically observed in highly trained athletes as a physiologic consequence of increased vagal tone. The variant of anterior (V1 to V3) ER characterized by "domed" ST-segment elevation and negative T wave raises problems of differential diagnosis with the "coved-type" electrocardiographic pattern seen in Brugada syndrome (BS). This study was designed to identify electrocardiographic criteria for distinguishing athlete's ER from BS. The study compared the electrocardiographic tracings of 61 healthy athletes (80% men, median age 23 ± 8 years), showing "domed" ST-segment elevation and negative T wave in leads V1 to V3, with those of 92 consecutive age- and sex-matched BS patients with a "coved-type" electrocardiographic pattern. The electrocardiographic analysis focused on the ST-segment elevation at J point (STJ) and at 80 milliseconds after J point (ST₈₀). Athletes had a lower maximum amplitude of STJ (1.46 ± 0.7 vs 3.25 ± 0.6 mm, p <0.001) and lower STJ/ST₈₀ (0.8 ± 0.3 vs 1.6 ± 0.3, p <0.001). All patients (100%) with BS showed a downsloping ST-segment configuration (STJ/ST₈₀ >1) versus only 2 (3%) athletes (p <0.001). An upsloping ST-segment configuration (STJ/ST₈₀ <1) showed a sensitivity of 97%, a specificity of 100%, and a diagnostic accuracy of 98.7% for the diagnosis of ER. At multivariate analysis, STJ/ST₈₀ ratio remained the only independent predictor for ER (odds ratio 87, 95% confidence interval 19 to 357, p <0.001). In conclusion, the STJ/ST₈₀ ratio is a highly accurate electrocardiographic parameter for differential diagnosis between anterior ER of the athlete and BS. Our results may help in reducing the number of athletes who undergo expensive diagnostic workup or are unnecessarily disqualified from competition for changes that fall within the normal range of athlete's heart.
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http://dx.doi.org/10.1016/j.amjcard.2014.11.035DOI Listing
February 2015

[Diagnosis and therapy of arrhythmogenic right ventricular cardiomyopathy].

G Ital Cardiol (Rome) 2014 Nov;15(11):616-25

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that predisposes to the occurrence of ventricular arrhythmias and sudden death, particularly in the young and athlete. The classic variant of the disease predominantly affects the right ventricle, but phenotypic variants with early and prevalent left ventricular involvement ("left-dominant" ARVC) have also been described, supporting the concept that arrhythmogenic cardiomyopathy is a disease of both ventricles. The diagnosis is multiparametric and is based on a series of criteria, including ECG abnormalities, arrhythmic manifestations, morpho-functional abnormalities and genetic defects. The main goal of therapy is sudden death prevention. Implant of a cardioverter-defibrillator is the most effective strategy for prevention of sudden death, but it should be reserved to selected patients after accurate risk stratification, in view of the high complication rate over a long-term follow-up, the costs and the significant psychological impact of such therapy, especially in the young individual. The other therapies (either pharmacological or not) are palliative and aimed at relieving symptoms and preventing disease progression. The definitive cure of ARVC will be based on the discovery of the molecular mechanisms that are involved in the etiology and pathogenesis of the disease.
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http://dx.doi.org/10.1714/1694.18506DOI Listing
November 2014

Nonischemic left ventricular scar: sporadic or familial? Screen the genes, scan the mutation carriers.

Circulation 2014 Nov;130(21):e180-2

From the Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy (K.P., I.R., E.L., E.C., B.B., M.P.M., C.B.); Department of Radiology, Oncology, and Pathology, La Sapienza University, Rome, Italy (M.M., G.d.A.); and Radiology, Azienda Ospedaliera, Padua, Italy (B.G.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012515DOI Listing
November 2014

Compound and digenic heterozygosity predicts lifetime arrhythmic outcome and sudden cardiac death in desmosomal gene-related arrhythmogenic right ventricular cardiomyopathy.

Circ Cardiovasc Genet 2013 Dec 26;6(6):533-42. Epub 2013 Sep 26.

Departments of Cardiac, Thoracic, and Vascular Sciences, and Biology, University of Padua, Padova, Italy.

Background: Mutations in genes encoding for desmosomal proteins are the most common cause of arrhythmogenic right ventricular cardiomyopathy (ARVC). We assessed the value of genotype for prediction of lifetime major arrhythmic events and sudden cardiac death (SCD) in desmosomal gene-related ARVC.

Methods And Results: The overall study population included 134 desmosomal gene mutation carriers (68 men; median age 36 years [22-52]) from 44 consecutive ARVC families undergoing comprehensive genetic screening. The probability of experiencing a first major arrhythmic event or SCD during a lifetime was determined by using date of birth as start point for the time-to-event analysis, and was stratified by sex, desmosomal genes, mutation types, and genotype complexity (single versus multiple mutations). One hundred thirteen patients (84%) carried a single desmosomal gene mutation in desmoplakin (n=44; 39%), plakophilin-2 (n=38; 34%), desmoglein-2 (n=30; 26%), and desmocollin-2 (n=1; 1%), whereas 21 patients (16%) had a complex genotype with compound heterozygosity in 7 and digenic heterozygosity in 14. Over a median observation period of 39 (22-52) years, 22 patients (16%) from 20 different families had arrhythmic events, such as SCD (n=1), aborted SCD because of ventricular fibrillation (n=6), sustained ventricular tachycardia (n=14), and appropriate defibrillator intervention (n=1). Multiple desmosomal gene mutations and male sex were independent predictors of lifetime arrhythmic events with a hazard ratio of 3.71 (95% confidence interval, 1.54-8.92; P=0.003) and 2.76 (95% confidence interval, 1.19-6.41; P=0.02), respectively.

Conclusions: Compound/digenic heterozygosity was identified in 16% of ARVC-causing desmosomal gene mutation carriers and was a powerful risk factor for lifetime major arrhythmic events and SCD. These results support the use of comprehensive genetic screening of desmosomal genes for arrhythmic risk stratification in ARVC.
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http://dx.doi.org/10.1161/CIRCGENETICS.113.000288DOI Listing
December 2013

Electrocardiographic predictors of electroanatomic scar size in arrhythmogenic right ventricular cardiomyopathy: implications for arrhythmic risk stratification.

J Cardiovasc Electrophysiol 2013 Dec 9;24(12):1321-7. Epub 2013 Sep 9.

Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy.

Introduction: The extent of right ventricular (RV) electroanatomic scar (EAS) detected by endocardial voltage mapping (EVM) is a powerful invasive predictor of arrhythmic outcome in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Electrocardiogram (ECG) and signal-averaged ECG are noninvasive tools of established clinical value for the diagnosis of electrical abnormalities in ARVC. This study was designed to assess the role of ECG and SAECG abnormalities for noninvasive estimation of the extent and regional distribution of RV-EAS and prediction of scar-related arrhythmic risk.

Methods And Results: The study population included 49 consecutive patients (38 males, median age 35 years) with a definite diagnosis of ARVC and an abnormal EVM by CARTO system. At univariate analysis, the presence of epsilon waves, the degree of RV dilation, the severity of RV dysfunction, and the extent of negative T waves correlated with RV-EAS% area. Normal T-waves were associated with a median RV-EAS% area of 4.9% (4.5-6.4), negative T waves in V1-V3 of 22.0% (8.5-30.6), negative T waves in V1-V3 extending to lateral precordial leads (V4-V6) of 26.8% (11.5-35.2), and negative T waves in both precordial (V2-V6) and inferior leads of 30.2% (24.8-33.0) (P < 0.001). At multivariate analysis, the extent of negative T waves remained the only independent predictor of RV-EAS% area (B = 4.4, 95%CI 1.3-7.4, P = 0.006) and correlated with the arrhythmic event-rate during follow-up (P = 0.03).

Conclusions: In patients with ARVC, the extent of negative T-waves across 12-lead ECG allows noninvasive estimation of the amount of RV-EAS and prediction of EAS-related arrhythmic risk.
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http://dx.doi.org/10.1111/jce.12246DOI Listing
December 2013

Exercise-induced normalization of right precordial negative T waves in arrhythmogenic right ventricular cardiomyopathy.

Am J Cardiol 2013 Aug 3;112(3):411-5. Epub 2013 May 3.

Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.

Negative T waves (NTWs) in right precordial leads (V₁ to V₃) may be observed on the electrocardiogram (ECG) of healthy subjects but can also represent the hallmark of an underlying arrhythmogenic right ventricular cardiomyopathy (ARVC). It has been a consistent observation that NTWs usually become upright with exercise in healthy subjects without underlying heart disease. No systematic study has evaluated exercise-induced changes of NTWs in ARVC. We assessed the prevalence and relation to the clinical phenotype of exercise-induced right precordial NTWs changes in 35 patients with ARVC (19 men, mean age 22.2 ± 6.2 years). Forty-one healthy subjects with right precordial NTWs served as controls. At peak of exercise (mean power 149 ± 43 W, mean heart rate 83.6 ± 12.6% of target), NTWs persisted in 3 patients with ARVC (9%), completely normalized in 12 (34%), and partially reverted in 20 (57%). Patients with ARVC with or without NTWs normalization showed a similar clinical phenotype. The overall prevalence of right precordial T waves changes during exercise (normalization plus partial reversal) did not differ between patients with ARVC and controls (92% vs 88%, p = 1.0), whereas there was a statistically nonsignificant trend toward a greater prevalence of complete normalization in controls (56% vs 34%, p = 0.06). In conclusion, our study demonstrated that right precordial NTWs partially or completely revert with exercise in most patients with ARVC, and NTWs normalization is unrelated to the clinical phenotype. Exercise-induced NTWs changes are inaccurate in differentiating between ARVC patients and benign repolarization abnormalities.
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http://dx.doi.org/10.1016/j.amjcard.2013.03.048DOI Listing
August 2013