CPVT CASE PRESENTATION

& SHORT REVIEW

Ε. Συμεωνίδου, MD

Β΄ Παν Καρδιολογική Κλινική, Νοσοκομείο Αττικόν

ΛΗΨΗ ΚΛΙΝΙΚΩΝ ΑΠΟΦΑΣΕΩΝ ΣΤΙΣ

ΚΑΡΔΙΑΓΓΕΙΑΚΕΣ ΠΑΘΗΣΕΙΣ

Αθήνα 13/11/2015

No conflict of interest

HISTORY

26 yo ♀ Roma, with long term history of syncope & seizure episodes since 4 years old, triggered by exposure to physical or emotional stress.

Initially the diagnosis was epilepsy and she was receiving relevant therapy.

Admissions x to “Agia

Sophia” children’s Ηospital

for further investigation.

Family history (-)

12 leads ECG: normal

limits

Cardiac Echo: normal

limits

Exercise test suggestive of …. at 15

yo

HISTORY

Started on β-blocker

(metoprolol)

Because of

1. Bad compliance to

restriction of physical

activity and treatment

2. Insufficient β-blocker

dosage

Family was informed about risk of SCD and potential need for ICD implantation but they refused

She suffered for many years

recurrent presyncope &

syncope episodes

Is an ICD a Class I indication in this

pt?

A. Yes

B. No

C. Don’t know

Recent History

11 y later she suffered CA while talking on the phone and being very upset.

She was 6 weeks pregnant and been off β-blocker (betaxolol, a selective β1-blocker) for 10 days under her local gynecologist advice who was not well informed re her CPVT.

She was found on VF by paramedics, underwent very long-lasting CPR and transferred to the ICU of our hospital. SR restoration but with transient impaired LV function (EF 30%) under high dosage inotropes support.

Management

1 w post arrest, she was transferred to our Cardiac

Ward for further investigation and treatment.

Restoration of LV function, EF 55%, RV ok.

Cardiac MRI: nothing significant

In the meanwhile she

underwent uneventful abortion

as suggested by obstetrics.

12 leads surface ECG

Management

She was started on propranolol

While receiving the max tolerated dosage( 2mg/kg/d)

of β-blocker (propranolol) she sustained recurrent

episodes of

Management

Ca2 antagonist, verapamil was added to

propranolol

Titration to the max tolerable dosage of

the combination was achieved by

exercise test (110 bpm).

What’s the next step?

A. EPS

B. Amiodarone

C. Current combination,

(propranolol+verapamil) +new drug

D. ICD

ICD CxRAY

Eventually she received a DDDR ICD

and the recovery was uneventful.

4 mo later ICD appropriate firing while

dancing

Strict exercise restrictions and B-

blocker

8 MO LATER ICD INAPPROPRIATE

DISCHARGE x3 DUE TO AF

AF new discovery!

Verapamil stopped

Flecainideadded 50mg bd

5 years now, she is doing fine

FU Attikon Hospital Pacemaker Clinic

Much more compliant but depressed

No plans for family

Mother, father 1 sister and 2 brothers ECG, Ex- test, 24 h Holter monitoring, cardiac Echo ok

Genetic test obtained last

summer

awaiting results.

CPVT

Rare, malignant, inherited, arrhythmogenic disorder characterized by adrenergically induced VT without organic heart problem, manifesting as syncope or SCD.

The age of onset is usually between 2 and 12 years and the initial symptom is frequently syncope or cardiac arrest.

Prevalence in Europe 1/10000

Normal resting 12 leads ECG

DD LQTS7 (Andersen-Tawil), LQTS1, S Coupled variant TdP, IVF.

MUTATIONS IN CPVT→ DISRUPTION

OF CARDIAC Ca HOMEOSTASIS

1.Mutations in genes encoding the sarcoplasmic reticulum Ca(2+) release channel (RYR2) and (A)

2.In genes encoding the sarcoplasmic reticulum Ca(2+) binding protein cardiac calsequestrin (CASQ2) (the major Ca2+ storage protein in heart & a regulator of RyR2 channels (buffering protein) ) have been identified in CPVT patients. (R)

3. Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human as well.(R)

4.Calmodulin mutations –the central mediator of intracellular Ca signalling (A)

A Autosomal, R Recessive

Arrhythmogenesis mechanism

Vulnerable site: Purkinje

Bidirectional VT or PVT

CPVT-DIAGNOSIS

The diagnosis is based

on the demonstration

of polymorphic or

bidirectional ventricular

tachycardia associated

with adrenergic stress.

By exercise test &

Holter

Genetic testing can be

confirmatory in some

patients.

Epinephrine challenge and CPVT

Epinephrine challenge at doses of 0.05, 0.10, and 0.20 μg/kg per minute.

A test is considered + for CPVT if epinephrine provoked ≥ 3 beats of polymorphic or bidirectional VT and

borderline if polymorphic couplets, premature ventricular contractions, or NSM VT was induced.

Atrial arrhythmogenesis in CPVT – is there a

mechanistic link between sarcoplasmic reticulum Ca2+

leak and re-entry?

CPVT mutations

may present as a

form of

‘lone’ AF and that

abnormalities in SR

Ca2+ handling

can have a

causative role in

AF.

CPVT-Medications

MECHANISM BASED DRUG TREATMENT

B-blockers CORNERSTONE!

**Should be administered throughout pregnancy in affected women.

The reproducible induction of arrhythmia during exercise allows effective dose titration and monitoring.

Recommended drugs are nadolol- corgard(1-2.5 mg/kg/day) or propranolol (2-4 mg/kg/day)

Flecainide Direct RYR2 blocking

properties Flecainide inhibits arrhythmias by RyR2 channel block and by Na+ channel block.Adding flecainide to β-blocker treatment is the most effective next step. (1.5–4.5 mg/kg). The optimal dose between 150 and 200 mg/day (range 100 to 300 mg/day).

TARGETS THE

TRIGGER!

REDUCES THE PROBABILITY

THAT DADs

TRIGGER ARRHTHMIAS!

The efficacy of Ca2+-channel blockers in CPVT is disappointing,

Advice

2nd, advising against

participation in

competitive sports

and emphasizing the

great importance of

drug compliance are

essential.

In addition, CPVT

patients should be

informed that the use

of sympathomimetic

agents is

contraindicated.

Acute treatment

The most critical step

in the acute

management of

sustained VT,VT storm

or VF in a CPVT

patient to recognize

that it concerns a

CPVT patient

And the subsequent

instruction to

discontinue the

standard epinephrine

infusion in a

resuscitation setting.

IV b-blocker therapy 1st choice, analogous to

ventricular tachycardia storm of other etiology.

General anaesthesia is probably the last resort when b-

blocker therapy is not effective.

CPVT –WHEN ICD?

Class I indication with use of β-blockers for patients with CPVT who are survivors of cardiac arrest and have a good functional status.

Class IIa indication, patients with CPVT who experience syncope or sustained VT whilst receiving β- blockers

ICD Double-edged sword

It must always be remembered that children have a higher risk of ICD complications than adults.

Adrenergic stress connected with appropriate and inappropriate ICD interventions can result in electrical storm!!!!

Proarrhythmic

Proper ICD programming very significant!!!

LEFT CERVICAL SYMPATHETIC

DENERVATION.

Selective LCSD can now be done thoracoscopically.

1. Patients in whom β-blockers are contra-indicated or not adhered to.

2. An ICD cannot be placed or is not wanted.

3. Recurrent VT in those with an ICD despite maximal medical treatment

Catheter Ablation of Bidirectional Ventricular

Premature Contractions Triggering VF

in CPVT With RyR2 Mutation

Management CPVT

Stop Racism-It takes all of us!!!

Thank you

Eυχαριστώ