PREVENTING EMBOLIZATION IN INHERITED ARRHYTHMIA

DISORDERS

Pedro Brugada, MD, PhD.Chairman Cardiovascular Division

UZ-Brussel, Brussels.

Why this topic?

• Inherited arrhythmia disorders: An unknown cause of potential embolization.

• Guidelines on atrial fibrillation give no recommendations at all regarding inherited arrhythmia disorders (exception: HCM, WPW).

• NOACs may not be refunded for patients that may benefit the most.

EMBOLIZATION IN INHERITED ARRHYTHMIA DISORDERS

• Atrial: ATRIAL FIBRILLATION– Familial atrial fibrillation– Short QT– Long QT– Brugada syndrome– HCM– PRKAG with HCM or CCM– ANP gene mutations

EMBOLIZATION IN INHERITED ARRHYTHMIA DISORDERS

• Ventricular: STRUCTURAL– Left ventricular non-compaction– Post-op right ventricular dysplasia

28 cM

I:1 I:2

11.7 cM

6.6 cM 0.5 cM

FAMILIAL ATRIAL FIBRILLATIONREGION SHARED ON 10q2

AFFECTED

NON AFFECTED

DEAD

Familial Atrial Fibrillation

• Mean Age of Diagnosis 18 years• Range in age Diagnosis 1-35 years• Echocardiogram Normal• Chronic AF 41/42• Asymptomatic 36/42• Anticoagulation: 0• No embolization known: Future?

FAMILIAL ATRIAL FIBRILLATION CLINICAL FEATURES

Familial Atrial Fibrillation

SHORT QT syndrome.

• Atrial fibrillation in 40-45% of cases.• Youngest reported case: In utero.• No known embolization.

Gussak, Brugada P, Brugada J, et al. Cardiology 2000

LONG QT SYNDROME

• Atrial fibrillation: Yes, but incidence unknown

• Embolization: No reports

BRUGADA SYNDROME

• Atrial fibrillation: 20-25%

• Embolization: Yes

• Youngest patients: 3-14 y

Spontaneous atrial arrhythmias

→ Paroxysmal atrial fibrillation or SSS may be the first manifestation of Brugada syndrome: AJMALINE TEST!

→ Common cause of inappropriate ICD shocks:

14% of ICD recipients had inappropiate ICD shock because of asymptomatic, undiagnosed AF.

→ Marker of higher risk and/or of disease progress ?

ATRIAL FIBRILLATION IN CHILDREN WITH BRUGADA SYNDROME

• 3/8 pts in 1992 paper were children with AF.• 3/3 had SSS and were pacemaker dependent.• 2/43 children had total atrial standstill.• 1/43 with right and left atriomegally.• 4/43 (10%) with atrial fibrillation or flutter.

Transient ischemic attack in a 71 year-old man

First consultation

• Patient comes for second opinion after TIA

• Admitted at local hospital during his holidays because of speech difficulties Rx: Aspirine, simvastatine

• Previous history: Appendicectomy. Similar episode 8 years ago.

Admission at University Hospital

• Full neurological examination: Normal.• No carotid stenosis. CT, etc: Normal.• Cerebral MRI: Multiple microembolisms• Cardiological consultation: Normal, including

TEE, Holter, troponine, etc.

• Diagnosis: Cryptogenic TIA

ECG

Medical report local hospital

ECG

ECGs at admission

V1

Ajmaline test

TIA as a first manifestation of Brugada syndrome.

Follow-up ECGs

Follow-up

• DDD-ICD implanted.• Ablation of cavo-tricuspid isthmus.• Anticoagulation, sotalol.• No recurrence of AF after 2 years.

EMBOLIZATION IN INHERITED ARRHYTHMIA DISORDERS

• Ventricular: STRUCTURE– Left ventricular non-compaction– Post-op right ventricular dysplasia

Left Ventricular Non-compaction.

Intratrabecular flow in LVNC

Atrial Fibrillation in a 16 year-old boy.

AA, born 16-03-1995

• 1998: diagnosis of left ventricular non-compaction

Rx: Metroprolol, asymptomatic.

• 3/2011: Atrial fibrillation with fatigue and dyspnea Rx: Sotalol (vomiting, low blood pressure)

Amiodarone (hyperthyroidism) Verapamil, Lasix, Spirolactone, Warfarine.

Echocardiography

DATE LA (mm) LVEF (%) SPAP (mmHg)

19-1-2011 53 63 40

24-8-2011 56 61 70

23-9-2011 49 59 70

5-12-2011 (B) 57 30 75

After optimal medical RX

DATE LA (mm) LVEF (%) SPAP (mmHg)

19-1-2011 53 63 40

24-8-2011 56 61 70

23-9-2011 49 59 70

5-12-2011 (B) 57 30 75

21-12-11 - MI 3/4 ! 40 95

After optimal medical therapy

13-12-2011

• Severe heart failure with caquexia• Persistent atrial fibrillation• Diagnosis of LV non compaction confirmed• Severe mitral regurgitation with dilatation of

the annulus en massive tricuspid insufficiency

0

10

20

30

40

50

60

70

80

90 <3-month duration of atrial fibrillation prior to cardioversion

>12-month duration of atrial fibrillation prior to cardioversion

The longer one waits to initiate a rhythm-control strategy, the harder it is to regain sinus rhythm

1 month

P<.026 months

P<.07

Electrical cardioversion82%

36%

Patie

nts

in s

inus

rh

ythm

(%)

67%

27%<3m

Electroanatomical mapping

CRYOBALLOON ABLATION OF ATRIAL FIBRILLATION

Success rate of single procedure catheter ablation

● PAF ranges from 38% to 78%. Most series > 60%.

● Persistent AF ranges from 22% to 45%. Most centers < 30%.

Success rate of mutiple procedure catheter ablation

● PAF ranges from 54% to 80%. Most series > 70%.

● Persistent AF ranges from 37% to 88%. Most centers around 50%.

Centre for Heart and Vessel Disease, University Hospital Brussels

HYBRID THERAPY FOR ATRIAL FIBRILLATION

• Simultaneous endo and epicardial ablation.• Combination of RF and cryoablation possible.• Allows reduction of left atrium dimensions.• Allows exclusion of the left atrial appendage.

• Can be combined with other procedures: Valve repairICD implantation

• Success rate in persistent AF of 80-90%.

After CRT-D

DATE LA (mm) LVEF (%) SPAP (mmHg)

19-1-2011 53 63 40

24-8-2011 56 61 70

23-9-2011 49 59 70

5-12-2011 (B) 57 30 75

21-12-11 - MI 3/4 ! 40 95

14-5-2012 - MI 1/4 62 60

After CRT-D

What about the future?

• Embolization• Heart failure • Atrial and ventricular arrhythmias.

Best strategy to treat AF in inherited arrhythmia disorders?

• Medical: Disease specific therapies and disease specific pro-arrhythmic drugs.

THE MIRROR-IMAGE PATHOPHYSIOLOGY

• Electrical: Pacing for SSS.• Ablation: RF ablation versus cryoablation.• Surgical: Hybrid therapy for persistent AF.

ISSUES ABOUT ANTICOAGULATION IN INHERITED ARRHYTHMIA DISORDERS.

• IADs not diagnosed as the cause of AF.• Incidence and prevalence of AF in IADs unclear.• Indications for anticoagulation in IADs unclear.• Role of CHADS2 and CHAD2DS2-VASC scores?

With AF, the younger you are the greater the risk?

CHADS2 y/risk y to 100%

0 2 50

1 3 33

2 4 25

3 6 16

4 9 11

5 12 9

6 18 6

0

10

20

30

40

50

60

y/risk y to 100%

Conclusions

• Because of the low embolization score NOACs are not reimbursed for patients with IADs in spite of the high cumulative life-long risk.

• Studies to understand and guidelines on how to manage AF in IADs are urgently required.

• In young individuals with AF, and in those with a structurally normal heart, IADs have to be excluded as the cause of AF.