bigual@eresa.com

Cardiac magnetic resonance in arrhythmogenic cardiomyopathy. A multicenter study.

BEGOÑA I. MUÑOZ MD1,2; Esther Zorio,2,3 MD,PhD; Jordi Estornell 1, MD,PhD; Alicia Maceira 1, MD,PhD; Fernando Mas-Estelles 1, MD; Pablo Nogues-Melendez 1, MD; Almudena Lucas-Perez 1, MD; Maria pilar lopez-lereu 1, MD; Diana Domingo-valero 3

AUTHOR BLOCK

Unidad de imagen cardiaca ERESA.1Unidad de muerte súbita familiar.2Servicio de cardiología.3 .Hospital universitari i politecnic la FE.Valencia

BACKGROUND

Biventricular (BVAC) and left dominant (LDAC) forms had recently been included in the spectrum of arrhythmogenic cardiomyopathy (AC).

Sen-Chowdhry S, et al .Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity.J Am Coll Cardiol. 2008 Dec 16; 52(25):2175-87.

Sen-Chowdhry S et al. Cardiovascular magnetic resonance in arrhythmogenic right ventricular cardiomyopathy revisited: comparison with task force criteria and genotype. J Am Coll Cardiol 2006

Left ventricular late gadolinium enhancement is a finding that allows AC diagnosis with better sensitivity and especifity than other imaging parameters.

OBJECTIVE

We aim to describe in this setting using cardiac magnetic resonance imaging (CMR) :

Patterns of ventricular involvement

Patterns of late gadolinium enhancement (LGE)

(Exon 24 DSP Q1866X, Exon 23DSPE1039fs)

METHODS

STUDY DESIGN

Retrospective study reviewing records from the magnetic resonance data base (Filemaker Pro, versión 8.1) of 3 hospitals ( 2006-2010)

Inclusión criteria : 1. Imaging diagnosis of MCA made empirically by radiologist 2. Clinical diagnosis of MCA made by cardiologist.

Patients without clinical diagnosis of AC are excluded

METHODS

CLINICAL DIAGNOSIS

Clasical forms of AC: Based on Task Force Criteria

Biventricular and left forms of AC: Epicardial late gadolinium enhancement ( LGE) in left ventricle (LV) and also clinical diagnosis in a first degree relative.

Index cases of biventricular or left dominant forms:Epicardial LGE and also confirmatory mutation in desmosomal gene.

METHODS

CMR PROTOCOL

Cine imaging in LV using a breath hold steady state free precession sequence ( FOV: 33-35 cm Thick: 8mm, RT 2,8, ET: 1,2 ms flip angle 58º, Phases:20 ) in 2, 3, and 4 chamber long axis plane as well as short axis plane from base to apex.

Cine imaging in RV: With the same sequence in outflow tract and 4 and 2 chambers ( 6-8 slices)

Blackblood imaging with and without fat saturation in same planes as cine imaging using a breath-held double-inversion recovery fast spin echo sequence (FOV = 28-34 cm, Thick = 5 mm, TR = 2 heartbeats,TE = 41 ms, Matrix = 256 × 256

METHODS

Turbo Flash (Turbo fast low angle shot) Viabilility sequences: (Segmented, RT :700ms, ET:1.55 ms, Flip angle:45°, matriz 256 -192, FOV: 340 - 78 mm, grosor de thick :8 mm, 2 heart beats ) : in same planes as cine imaging adquired 5-8 minutes after IV administration of 0.1 mol/kg de gadolinium-DTPA.

CMR ANALYSIS of volumes and ejection fraction was made with QMASS 6.1.5 for windows ( Medis).

CMR PROTOCOL

METHODS

GENETIC SUDY

Screening of mutations in 5 main desmosomal genes

(plakoglobin, plakofilin-2, desmoglein-2, desmocolin-2 and desmoplaKin) in periferical blood ADN by conventional secuencing with ABI Prism 3100 sequencer ( Applied Biosystems).

Causative mutation: (In index cases) were considered those previously described or another news that cause significant changes in protein structure and function.

Confirmatory mutation: (in relatives) Those previously identified in index case.

METHODS

VARIABLES

Presence of late gadolinium enhancement (LGE) in left ventricle (LV) and right ventricle (RV);

Biventricular dilatation (LVEDVi ≥98ml/m2 and RVEDi ≥100ml/m2.

Dysfunction: LV ejection fraction (LVEF) ≤ 55% and RV EF≤ 45%

Impaired segmental contractility in RV ( aneurysms or diastolic bulging) and LV.

LEFT AC

CMR STUDY OF PROBAND

First CMR diagnosis of myocarditis

Six months later, syncopal ventricular tachycardia with right bundle branch morphology

LEFT AC

CLINICAL EVOLUTION

LEFT AC

CT STUDY

ICD implant, control CT

LEFT AC

FIRST DEGREE RELATIVES STUDY

Pathological EKG, with subepicardial ischemia V4-V6

LV not dilated ( IVTDVI 93ml/m2) EF:42%.RV not dilated (IVTDVD 71ml/m2) EF: 53%.

FIRST DEGREE RELATIVES STUDY

LEFT AC

LEFT AC

FIRST DEGREE RELATIVES STUDY

LGE in LV: inferior,inferolateral,lateral, anterior at basal, middle and apical regions

A) Basal short axis turbo-flash viability sequences with and without fat supression: epicardial fibrosis.B) CT images MPR in basal short axis showing epicardial fibrofatty infiltration.

LEFT AC

A A

BTSE t1 Haste irm

BIVENTRICULAR AC

E1039fs desmoplakin

CARRIER E1039fs desmoplakin

Cine imaging in proband

Viability sequences in first degree relative

36 years male ,resuscitated sudden death

Subtricuspid aneurysm, with late gadolinium enhancement , normal RV and LV volumes and function.

BIVENTRICULAR AC

CMR STUDY IN PROBAND

Epicardial LGE anterior, lateral, inferior in basal, middle and apical regions .

BIVENTRICULAR AC

CMR STUDY IN PROBAND

RESULTS

BASELINE CHARACTERISTICS OF POPULATION SAMPLE

RVAC LVAC BVAC

N:26Familiar studysymptoms

Syncopepalpitationsdyspnoea SVT or sudden death

Males:17pAge: 40+16Meet TFC

199420002010

3p with normal RVTDVI and EF

RESULTS

PATTERNS OF BIVENTRICULAR INVOLVEMENT

Impaired segmental contractility

Score of biventricular involvementLV RV

Dysfunction

Dilatation

Late gadolinium enhancement

Score= ∑ of traits

RESULTS

Number of patients

Patients number

BIVENTRICULAR INVOLVEMENT SCORE

PATTERNS OF BIVENTRICULAR INVOLVEMENT

Average:0,46 +1,6

N:26p

RESULTS

19 (79%), patients with RV involvement.

13 (54%) pacientes with RVTDVi>100 ml/m2 and 6 patients (25%) without dilatation only aneurysms or diastolic bulging.

PATTERNS OF VENTRICULAR INVOLVEMENT

Number of patients

24p

19p

RESULTS

11 patients (42%), had genetic study five of them had only lV involvement and six were biventricular forms

Six desmoplakin mutations ,Two double mutations desmoplakin and desmocolin and a patient with two variants (desmoplakin and plakofilin)

Two patients with biventricular forms had not confirmatory mutation

GENETIC SUDY

Distribution of traits in population sample

RESULTS

Number of patients

24

1313 13 13

32

LVEF<40%

75%

RESULTS

10p

4p4p

Patterns of late gadolinium enhancement

75%

RESULTS

Patterns of late gadolinium enhancement

17p

7p

15 p

15p

9p

LIMITATIONS

Retrospective design : Parameters like late gadolinium enhancement in RV or diastolic bulging are technically demanding and may be underestimated with this design.

Selection bias: Inclusion is mainly done by CMR, therefore population sample could have major structural involvement .

The most frequent abnormal finding is LV LGE, while the least frequent is LV dilatation.

LV involvement is a frequent finding in this sample of AC.

LGE was more frequently subepicardial and located in inferior and inferolateral walls.

Biventricular involvement with right predominance is the most frequent finding in this sample of AC.

CONCLUSIONS