cardiac arrhythmia in thalassaemia limassol, 24 – 26 october 2012 malcolm walker

Cardiac Arrhythmia in ThalassaemiaLimassol, 24 – 26 October 2012

Malcolm WalkerUniversity College and the Heart Hospitals, LondonClinical Director Hatter Cardiovascular Institute

Cardiac Arrhythmias in thalassaemia

• Plan of talk1. Historical aspects2. Relationship to iron overload3. Clinical Management: Principles & Investigation4. Specific arrhythmia5. Technology: Ablation & Devices

Cardiac Arrhythmia in thalassaemia

1. Historical aspects

History: incidence of arrhythmia & ECG changes thalassaemia, transfused but not chelated

Age Normal ECG % LV hypertrophy %

Rhythm abnormality %

Heart block %

5-10 67 33 6 6

11-15 39 28 44 6

16-20

30 40 50 40

21-30 12 62 19 19

TOTAL 39 40 27 14

Adapted from Ehlers et al 1980


2. Relationship to iron overload

● 652 patients with -thalassaemia

● Mean age 27 yr

● Excluded those with heart failure (HF) at first scan

Arrhythmia and myocardial iron assessed by cMR T2*


Threshold for arrhythmia T2*<20ms

Types & frequency:

● AF 78 (12%)

● SVT 14 (2%)

● VT 5 (<1%)

● VF 1

Adapted from: Marsella et.al. Haematologica 2011; 96: 515

MIOT study group: gender differences

Italian MIOT Cohort

Men

LV D

ysfu

nctio

n

Wom

en L

V Dys

funct

ion

Men

arrh

ythm

ia

Wom

en a

rrhyt

hmia

0

5

10

15

20

25

p=0.14F

req

uen

cy %

Adapted from: Marsella et.al. Haematologica 2011; 96: 515

MIOT study group: T2* and cardiac arrhythmia

Conclusions •Incidence of arrhythmia very low in this Italian cohort•25 out of 776 patients (3.2%); compared to overall 15% incidence in 1 year (UK cohort; Kirk et al 2009)•No statistical relationship with heart iron by T2* in Italian group; clear cut risk associated with T2* in UK cohort (Kirk et al 2009)


Reasons for differences between Italian and UK

patients?•Italian cohort more recent•Overall lower T2*; very few patients with T2* < 20 ms•More patients on combination Rx (DFO + DFP)


AF in thalassaemia major – UCH clinic

• 80 consecutive clinic attenders 2011-2012 Mean age 38 yr; 51% female

AF current 8.75% History of AF or pAF 33.7% DM 48.7% Thyroid 22.0% Hep C (ever) 15.0% Heart failure in last 12 months 10.0%

AF in thalassaemia – UCH clinic

55 11 10

% incidence

Heart iron load by current cMR T2*


patients?

AF in thalassaemia – UCH clinic Relationship between iron load & AF

T2* ms

Range 5 to 13 yr ago

P < 0.05

Walker et al unpublished observations


patients?

•Atrial fibrillation (AF) occurs late in life and reflects past

history, not current iron status

AF in thalassaemia – UCH clinic Relationship between iron load & AF

T2* ms

Range 5 to 13 yr ago

P < 0.05

Walker et al unpublished observations

AF in thalassaemia – UCH clinic Risk factors for AF

Diabetes link 71% of those in AF now have DM 69% of those with a history or pAF have DM

LA size (by area by ECHO – cMR volumes awaited) No clear correlation with AF

Current LV function (systolic, by EF) No clear correlation with AF Correlation with previous episode of LV dysfunction


3. Clinical Management principles & investigation

Clinical aspects of arrhythmia in thalassaemia

• Symptoms Palpitation Breathlessness Dizziness or near fainting Collapse

• There is a mismatch between symptoms & severity of arrhythmia

• “Trivial” problems may cause immense anxiety• Potentially severe arrhythmia may cause only minor

complaints (or no symptoms)


• Symptoms Palpitation

Breathlessness Dizziness or near fainting Collapse

Near fainting, loss of consciousness or collapseAlways need to be taken very seriously


• Management requires1. Diagnosis of the arrhythmia causing the

symptoms ECG Holter ambulatory monitor – 24 hr or longer

• Techniques which may be useful Implantable loop recorder – “Reveal” device Analysis of repolarisation (QT and JT dispersion) Electrophysiology study

Clinical aspects of arrhythmia in thalassaemia – the clinic ECG

Atrial Fibrillation AFSupraventricular tachycardia SVT

Ventricular ectopic VE



symptoms ECG Holter ambulatory monitor – 24 hr or longer Event recorders

• Techniques which may be useful Implantable loop recorder – “Reveal” device

Clinical aspects of arrhythmia in thalassaemia – the Holter 24hr ECG

Holter 24 hr ECGPatient aged 27 yrSymptom: palpitation + dizzinessShows Ventricular tachycardia VT

Holter ambulatory ECG screening

• Holter screening failed to predict 2 patients

From Qureshi et al. Annals NY Acad Sci 2005

•Significant arrhythmia detected in 15% patients (n=4)•Holter screening failed to predict 2 patients who went on to have significant arrhythmia•30% of the patients with a normal Holter had symptoms

•CONCLUSION•Routine screening of TM population with Holter not sensitive nor specific•Need to consider newer technologies – event recorders, ILR



symptoms ECG Holter ambulatory monitor – 24 hr or longer Event recorders

• Techniques which may be useful Implantable loop recorder – “Reveal” device


• Management requires1. Diagnosis

However, making the ECG diagnosis is not enough on its own

• Importance of the arrhythmia depends critically on knowledge of the underlying cardiac status

1. Ventricular function; structural heart defects2. Iron burden (cMR T2*)3. Pro-thrombotic tendency


• Management requires1. Precise diagnosis2. Knowledge of underlying cardiac status

Ventricular function & cardiac structure by ECHO Iron burden (T2*) by cMR

An ECHO + cMR are URGENT when1 Ventricular arrhythmia2 Poorly tolerated AF3 Symptoms include loss of consciousness/ collapse/ heart

failure

Clinical aspects of arrhythmia in thalassaemia - conclusions

• ECG Necessary baseline at least every 12/12 At every cardiovascular assessment

It tells us more about the heart than just arrhythmia

• Holter 24hr ECG Useful to investigate symptoms Poor as a screening tool in asymptomatic well

chelated TM patients with good LV function


4. Specific arrhythmiaVTAF

Specific arrhythmiaTachycardia – ventricular (VT)

• Ventricular tachycardia (VT) or broad complex tachycardia



This is a medical emergency Input of emergency physicians/ cardiologists Immediate cardioversion if in collapse or shock

It always complicates severe iron overload It may respond to iv chelation with DFO

iv DFO must be started immediately Combination treatment may be indicated



Once acute event controlled Consider implantation of ICD

Poor LV function not improving with iv chelation VT occurs without high iron overload – look for another

cause! ICD must be MRI compatible

Specific arrhythmiaAtrial Fibrillation AF

• AF: the commonest arrhythmia Paroxysmal Persistent Permanent

Specific arrhythmia: Atrial Fibrillation Risk to patient: Heart Failure

1 Cardiac decompensation/ overt heart failure Most likely when AF first appears - when heart rate is

high Target treatment to:

1. Control rate2. Restore normal sinus rhythm

Check, urgently if significant heart failure signs:1. LV function by ECHO2. Cardiac iron status by cMR T2*3. Thyroid function etc.

Specific arrhythmia: Atrial Fibrillation Risk to patient: Stroke

2 Stroke risk depends critically on: Prothrombotic status Structural heart disease Impaired LV Higher risk if AF is persistent or permanent or

frequent paroxysms of more than 12 hr duration1. Restore normal sinus rhythm where possible2. Anti-coagulation with warfarin (INR 2.5) or new agents

Check1. Cardiac ECHO for LA size, LV function, valve disease

Specific arrhythmia AF – special circumstances

1.Complicating cardiac failure2.Precipitating cardiac failure3.In iron loaded TM with good LV function4.In non iron loaded TM with good function


1. Complicating cardiac failure2. Precipitating cardiac failureThese are urgent situations requiring admission

1. Consider TOE guided DC Cardioversion2. Itensify Rx: iv DFO: 24r x 7 days plus DFP (?)3. Conventional long term management: aim to

prevent further attacks1. Betablockers2. Amiodarone (short to medium term)3. Anticoagulation


3. In iron loaded TM with good LV function4. In non iron loaded TM with good functionThese are non-urgent situations requiring

1. Consider TOE guided DC Cardioversion after 4 weeks anticoagulation

2. Itensify chelation Rx: if iron overloaded3. Conventional rate & rhythm control

1. Betablockers2. Rate lowering calcium channel blockers

4. Anticoagulation with warfarin or new agents

Specific arrhythmia AF – long term prevention strategy

• Long term prevention strategies of AF Medication: generally poor at long term prevention

Effective drugs potentially too toxic (Amiodarone) Less toxic drugs often less effective (Beta-block, Flecainide)

Thalassaemia population may have an advantage, if AF complicates iron overload. Removing iron may effectively prevent AF for many years (?)

Consider ablation and other therapies

Catheter based ablation for AF

• Cardiac catheter based techniques• Complex & time consuming (2 to 4hr)• Often GA required• Specialist EP cardiologists & service

• Success rates 70 to 80%• Recurrence rates approx 15% at 1 year• Risk of Stroke, cardiac perforation 1% to 2%

Complications and success rates may be different for thalassaemia population


• Rhythm control by ablation General success rates 70% to 80% “cure” 15% need second ablation

• In TM population Experience is young Anecdotal evidence of much higher recurrence

rates

AF: Interventional techniques to reduce stroke risk

• Left atrial appendage occluder Catheter based technique Reduces risk of stroke

• Structural defect closure Patent foramen ovale (PFO) closure

If patient has strong pro-thrombotic tendency

Bradycardia & heart block in thalassaemia

• Complete heart block common in the past is rare today

Bradycardia & heart block in thalassaemia

• Complete heart block is rare• Mandates the use of a pacemaker

Historically this would prevent the use of cMR forever!

“Patients and the implanting community deserve nothing less than devices that are safe by design and not by chance.”

– J. Rod Gimbel, MD, FACC Emanuel Kanal, MD, FACR

For more information visit: http://www.medtronic.com/mrisurescan/

http://www.medtronic.com/mrisurescan/

4 chambers

LA

LVLead

Signal alteration

RA

RV

cMR safe pacemakers

Arrhythmia and thalassaemiaConclusions

• Complex pathophysiology, which may be changing as TM population ages

• Practical management issues largely revolve around intensified chelation, as this may control problem

• Role of EP techniques needs to be fully defined• Devices need to be cMR compatible

cardiac arrhythmia in thalassaemia limassol, 24 – 26 october 2012 malcolm walker

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