CRT IN PAEDIATRICS AND CONGENITAL HEART DISEASEsaheartcongress.org/wp-content/uploads/2017/12/11.-16h00-Ballroom... · sudden cardiac death ... •Finding reliable minimally invasive

A Square Peg in a Round Hole:

CRT IN PAEDIATRICS AND CONGENITAL HEART DISEASE

Adele Greyling

Dora Nginza Hospital, Port Elizabeth

SA Heart November 2017

What are the guidelines based on?• MADIT-II was a breakthrough trial in 2002

• Prophylactic ICDs save lives in patients with ischaemic heart disease.

• 31% Reduction in the risk of death when compared to conventional medical therapy alone (p = 0.016).

• BUT respective 39% & 58% increase in risk of first & recurrent HF hospitalisations during follow-up.

•“These findings should direct more attention to the prevention of HF in patients who receive an ICD.”

MADIT-IISize: 1218 U.S. patients

Endpoint: All-cause mortality (patient follow-up = 20 months)

Published: NEJM 2002

•Mode of death substudy showed •Death from tachyarrhythmia was reduced by 60% in the device arm, without appreciably changing the mortality from other causes.1

• HF remained a major cause of mortality these Class II/III HF patients.

SCD-HeFTSize: 2521 patients in North America

and New Zealand

Endpoint: All-cause mortality

Published: NEJM 2005

• Proved both ischemic and non-ischemic heart failure patients benefit from SCD protection.

• 23 % Reduction in the risk of all-cause mortality when using an ICD, in combination with conventional drug therapy (CDT), when compared to CDT alone (p = 0.007)

1 Packer DL, Bernstein R, Wood F, et al. Impact of Amiodarone versus implantable cardioverter defibrillator therapy on the mode of death in congestive heart failure patients in the SCD-HeFT trial. Heart Rhythm. 2005;2:S38. Abstract AB20-2.

• CRT-D can save lives in late-stage HF patients (Class III-IV).

• CRT produced symptomatic relief, QoL, etc. that an ICD (and even CDT) can't provide.

• But that pump failure was still the most common cause of death – urging us to want to prevent or slow any patient’s progression to this stage of symptomatic heart failure.

COMPANIONSize: 1520 U.S. patients

Endpoint: All-cause mortality or first

hospitalization

Published: NEJM 2004

20% Reduction in the risk of all-cause mortality or first hospitalization with CRT-D, in combination with CDT, compared to CDT alone (p = 0.011)

5

Key Learning

MADIT II

COMPANION

SCD-HeFT

Ability to save lives from sudden cardiac death…

…heart failure remains an issue

Bottom Line:

Multicenter Automatic Defibrillator Implantation Trial with Cardiac

Resynchronization Therapy (MADIT-CRT)

Retrospective studies of CRT-D in NYHA Class I/II patients showed improvement in echocardiographic variables,

Suggesting a potential role for CRT-D earlier in the disease process

MADIT-CRT was undertaken to determine if early intervention with CRT-D in patients with asymptomatic or mild heart failure could reduce death and heart failure events

Higgins et al, JACC (2001)Abraham et al, Circulation (2004

Our patient cohort

• Seldom have LBBB

• Often have pre-existing ventricular pacing with pacing associated HF

• Often have a RBBB, IVCD

• May have a systemic RV

• May have had previous surgery

• May have a single ventricle

• Children with DCMO narrow window of opportunity

CRT in Paediatrics• Due to rarity and diversity of disease - “mixed-bag” of low “N” substrates

and difficult-to-generalize results

• Only 8 studies have been published

• All retrospective with < 110 patients

• Seven single center studies, 5 had < 15 patients

• None focused exclusively on children• CHD included in all, and 3 studies focused entirely on CHD

• None included comparison with matched controls on medical management

CRT in Paediatrics• A total of 380 patients are reported, ages range from 0.4 to 73.8 years.

• Only 89 patients (23.4%) had primary cardiomyopathies, 291 patients (76.6%)

had congenital heart disease.

• Attempts to resynchronize the RV, SV via multipoint pacing, as well CRT via

BiV pacing, was assessed

• The indications for CRT for these studies were not defined.

• Severe, symptomatic, systolic heart failure was present.

• Systemic ejection fraction generally <30%, with QRS duration > 160 msec.

McCanta et al; Progress in Pediatric cardiology 2016

Is CRT the wrong tool for paediatric patients?

• Only 9.2-16% had classic left bundle branch block

• and only 12-37% had reported NYHA Class III or IV

• Only 59% of patients had a systemic LV

• Even in the 52 patients with DCMO without CHD

• no patients met the Class I indication for CRT at the first

visit

• Only 2 did at the second visit

The phenomenon of “nonresponse”

• Rate of < 10-29% paediatric/CHD studies vs up to 40% in adult CRT studies

• ? Due underlying heart failure substrate which is more commonly pacing-induced dyssynchrony vs ischaemic cardiomyopathy

• ? Selection bias, ? more rigorous selection in paediatric studies• Nonrepsonse seen more in less severe cases with less room for

improvement• Or, very severe cases with “burn-out heartfailure”

McCanta et al; Progress in Pediatric cardiology 2016

• Patient with a block on the side of the systemic ventricle (LBBB for systemic LV and RBBB for systemic RV) were most likely to respond

• Systemic LV had better outcome than systemic RV

• Single ventricle with multisite pacing and widely spaced electrodes, benefits were reduced but there was still improvement

Janousek J, et al. Heart 2009;95:1165–71.

The phenomenon of “nonresponse”

Benefit on all cause mortality

• The mortality is 6% in paediatric studies vs >20% in adult studies• Less non cardiac co-morbidity, better general health and more resilience • Caveat : short follow up times

not compared to controls.

• 17-40% of patients could be removed from the transplant list with the addition of CRT.

This points to the appropriate utilization of CRT in the pediatric population

Technical aspects in CRT implantation

• CRT is achieved by pacing both ventricles nearly simultaneously• More efficient contraction,• Less AV valve insufficiency by ventricular volume reduction and more efficient

activation of papillary muscle apparatus

• Transvenous placement of an endocardial lead in a left lateral cardiac vein via the coronary sinus• Longer procedure times, increased complications• May not be able to cannulate the CS• May cause dissection or perforation of the CS• May cause dislodgement of existing on newly placed endocardial leads

Technical aspects in CRT implantation

• Transvenous endocardial pacing limited due to patient size and anatomy

• Patients < 20kg are at increased risk of longterm complications: venous thrombosis, infection, and lead failure necessitating lead extraction.

• 3 leads worse than 2 leads

Technical aspects in CRT implantation

• 9F sheath for LV lead

• CS may be difficult to cannulate or not accessible at all, even then appropriate positioning might not be possible

• Sheaths, wires and leads designed for adults (angle, diameter, length)

• No official guidelines, but transvenous system generally reserved >50kg

• Need GA

• Risks of re-sternotomyMcCanta et al; Progress in Pediatric cardiology 2016

The future of CRT in Paediatrics

• Minimize RV pacing

• Preventing the development of electromechanical dyssynchrony

• Resynchronization of the right ventricle

Minimize RV pacing

• Pacing the ant RV causes dyssynchrony similar to intrinsic LBBB

• 46% of patients in CRT studies had congenital CHB and epicardialpacing

• Carefully consider the indication for pacing

• Minimise RV pacing, long AV delay

• LV apical pacing as apposed to ant RV epicardial leads

• Endovascular septal pacing

• ? Prophylactic CRT

Preventing the development of electromechanical dyssynchrony

• Finding reliable minimally invasive markers for early dyssynchrony

• CRT placement prior to a significant decrease in ejection fraction or increase in QRS duration may be valuable

• Strain imaging on echocardiography/MRI carries significant promise

• identification of dyssynchronous segments,

• selective lead placement during implant,

• may be used as a means to optimize CRT during follow-up programming

• The primary limitation of strain imaging - algorithms are designed to analyze the left ventricle only.

Preventing the development of electromechanical dyssynchrony

• CMRI with late gadolinium enhancement can be used to evaluate the myocardium for inflammation and/or scarring

• Regions of late activation can be targeted for lead placement, and regions of scar could be avoided

• With whole body MRI-conditional systems, MRI can be used for the evaluation for response

Resynchronization of the right ventricle

• Dyssynchrony, HF in CHD frequently involves the RV – TOF prototype

• Substrates for electromechanical dyssynchrony• Elevated systolic and diastolic RV pressures causing subendocardial

ischemia,• Surgical scars at the ventricular septal defect and occasionally the

outflow tract, • Surgically induced right bundle branch block

• Prompted attempts in RV resynchronization• By "preexciting” the RV with early RV-only pacing in RBBB• Or, even with biventricular pacing in tetralogy of Fallot

Resynchronization of the right ventricle

• These concepts have also been applied in other CHD with systemic RV, including d-TGA palliated by atrial switch procedures and HLHS

• With the hope that a synchronous RV will have improved output and possibly decreased arrhythmia risk

• Studies have shown promising improvements in QRS duration, systemic ventricular ejection fraction, and functional status.

McCanta et al; Progress in Pediatric cardiology 2016

Conclusion

• Heterogeneous group of patients

• No clear guidelines

• No reliable screening tool

• Technically challenging procedure

• But… rates of non-responders comparable to adult IHD/DCMO

• Should be considered in patients with CHD and failing RV

ConclusionTake home message :Prevention is better than cure!

• Prevent iatrogenic dyssynchrony with pacing configurations

• Prophylactic placement of CRT

• In patients with expected life-long pacing (CHB)• Or, patients with CHD whom have another indication for pacing

and/or ICD with a high expected percentage RV pacing

• Development of reliable non-invasive measures of dyssynchrony is needed, that may allow for the earlier placement of CRT systems prior to QRS prolongation or ejection fraction decrease.

Thank you!