Cardiac Resynchronization TherapyCardiac Resynchronization Therapy* in Patients With Severe Systolic...

Cardiac

Resynchronization

Therapy

Reda Deyab, MD.

Associate Professor of Cardiology

Cairo University

Heart failure is a clinical syndrome resulting

from a structural or functional cardiac disorder

that impairs the ability of the ventricle to fill with

or eject blood commensurate with the needs of

the body, or that precludes it from doing so in

the absence of increased filling pressure.

Heart failure affects approximately 4.9 million

persons in the USA, and more than 500 000 new

cases of heart failure are reported each year.

In the USA, approximately 300 000 persons die of

heart failure each year.

Heart failure is a considerable economic

burden, and the costs of hospitalization represent

65–75% of the total cost of treating a patient.

In the USA, the annual expenditures for

hospitalization for heart failure exceed $40

billion.

Heart failure is the end stage of all diseases of the

heart and is a major cause of morbidity and

mortality.

Disorders of the conduction system are often

associated with myocardial dysfunction. Indeed,

prolongation of QRS (120 ms) occurs in 14–47%

of patients with heart failure and is generally

accepted as occurring in approximately 30% of

all patients with low-LVEF heart failure

Left bundle branch block (LBBB) occurs more

commonly than right bundle branch block

(RBBB) (25–36% vs 4–6%, respectively).

Prevalence of Inter- or

Intraventricular

Conduction Delay

1 Havranek E, Masoudi F, Westfall K, et al. Am Heart J 2002;143:412-417 2 Shenkman H, McKinnon J, Khandelwal A, et al. Circulation 2000;102(18 Suppl II): abstract 2293 3 Schoeller R, Andresen D, Buttner P, et al. Am J Cardiol. 1993;71:720-726 4 Aaronson K, Schwartz J, Chen T, et al. Circulation 1997;95:2660-2667 5 Farwell D, Patel N, Hall A, et al. Eur Heart J 2000;21:1246-1250

IVCD 15%

IVCD >30%

General HF Population1,2 Moderate to Severe HF Population3,4,5

Increased Mortality Rate with

LBBB Increased 1-year mortality with

presence of complete LBBB

(QRS > 140 ms)

Risk remains significant even

after adjusting for age,

underlying cardiac disease,

indicators of

HF severity, and HF

medications

Baldasseroni S, Opasich C, Gorini M, et al. Am Heart J 2002;143:398-405

11.9

5.5

16.1

7.3

0

5

10

15

20

All Cause Sudden Cardiac

All patients N=5517

LBBB N=1391 HR* 1.70

(1.41-2.05)

HR * 1.58

(1.21-2.06)

Cause of Death

1-Y

ear

Mo

rtality

(%

)

* HR = Hazard Ratio

Based on left ventricular (LV) ejection fraction

(LVEF), patients with heart failure can be

divided into those with primarily systolic

dysfunction and those with diastolic

dysfunction.

Patients with a low LVEF, usually <45%, are

considered to have systolic dysfunction.

Proposed Mechanisms of

Cardiac Resynchronization

Cardiac Resynchronization

Improved Intraventricular

Synchrony

Improved Atrioventricular

Synchrony

Improved Interventricular

Synchrony

Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445

Summary of Proposed

Mechanisms

Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445

Intraventricular

Synchrony

Atrioventricular

Synchrony

Interventricular

Synchrony

LA

Pressure

LV Diastolic

Filling

RV Stroke

Volume

LVESV LVEDV

Reverse Remodeling

Cardiac Resynchronization

MR

dP/dt, EF, CO

( Pulse Pressure)

Proposed Mechanisms: Improved

Intraventricular Synchrony

dP/dt 1,3,4 EF1,5

Pulse Pressure 3,4 SV&CO1, 2

Improved Intraventricular

Synchrony1,2

MR1

LVESV1

LA

Pressure1

1 Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445 2 Søgaard P, Kim W, Jensen H, et al. Cardiology 2001;95:173-182 3 Kass D Chen-Huan C, Curry C, et al. Circulation 1999;99:1567-73 4 Auricchio A, Ding J, Spinelli J, et al. J Am Coll Cardiol 2002;39:1163-1169 5 Stellbrink C, Breithardt O, Franke A, et al. J Am Coll Cardiol 2001;38:1957- 65

Clinical Consequences of

Ventricular Dysynchrony Abnormal interventricular septal wall motion1

Reduced dP/dt3,4

Reduced pulse pressure4

Reduced EF and CO4

Reduced diastolic filling time1,2,4

Prolonged MR duration1,2,4

1 Grines CL, Bashore TM, Boudoulas H, et al. Circulation 1989;79:845-853. 2 Xiao, HB, Lee CH, Gibson DG. Br Heart J 1991;66:443-447. 3 Xiao HB, Brecker SJD, Gibson DG. Br Heart J 1992;68:403-407. 4 Yu C-M, Chau E, Sanderson JE, et al. Circulation. 2002;105:438-445.

Achieving Cardiac Resynchronization

Mechanical Goal: Atrial-synchronized bi-ventricular

pacing Transvenous Approach

Standard pacing lead in RA

Standard pacing or defibrillation lead in RV

Specially designed left heart lead placed in a left ventricular cardiac vein via the coronary sinus

Right Atrial

Lead

Right Ventricular

Lead

Left Ventricular

Lead

Echocardiographic parameters of intraventricular dyssynchrony.

• M-mode: Septal to posterior wall motion delay (>130 ms)

• 2D echo:

a. Aortic Pre-ejection interval >140 ms

b. Wall motion phase analysis (lateral delay >25°)

c. Contrast enhanced systolic regional fractional area

• TDI:

a. Difference in time to peak systolic velocity (4 segment >65 ms)

b. 12 segment LV dyssynchrony index >31 ms

c. Tissue tracking, strain and strain-rate imaging

d. TSI

• 3D

ACC/AHA/HRS 2008 Guidelines for Device-

Based Therapy of Cardiac Rhythm

Abnormalities

May 2008

Slide Set

Cardiac Resynchronization

Therapy* in Patients With Severe

Systolic Heart Failure

For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy.

For patients who have LVEF less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and AF, CRT with or without an ICD is reasonable for the treatment of NYHA functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy.

For patients with LVEF less than or equal to 35% with NYHA functional Class III or ambulatory Class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable.

I IIa IIb III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Cardiac Resynchronization Therapy*

in Patients With Severe Systolic

Heart Failure For patients with LVEF less than or equal to 35% with NYHA functional Class I or II symptoms who are receiving optimal recommended medical therapy and who are undergoing implantation of a permanent pacemaker and/or ICD with anticipated frequent ventricular pacing, CRT may be considered.

CRT is not indicated for asymptomatic patients with reduced LVEF in the absence of other indications for pacing.

CRT is not indicated for patients whose functional status and life expectancy are limited predominantly by chronic noncardiac conditions.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2012 ACCF/AHA/HRS Focus

Updates of 2008 guidelines

For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 150 ms, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class II, III or ambulatory Class IV on GDMT ( level of evidence A for NYHA III,IV and B for NYHA II).

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

CRT can be useful for patients who have left

ventricular ejection fraction (LVEF) less than or

equal to 35%, sinus rhythm, LBBB and a QRS

duration 129-149 ms for the treatment of New

York Heart Association (NYHA) functional Class II,

III or ambulatory Class IV on GDMT ( level of

evidence B).

New recommendation

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

CRT can be useful for patients who have left

ventricular ejection fraction (LVEF) less than or

equal to 35%, sinus rhythm, non LBBB and a QRS

duration greater than or equal to 150 ms for the

treatment of New York Heart Association (NYHA)

functional Class III or ambulatory Class IV on

GDMT ( level of evidence B).

New recommendation

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

CRT can be useful for patients who have AF with

left ventricular ejection fraction (LVEF) less than or

equal to 35% on GDMT if (A ) AV nodal ablation

or pharmacologic rate control will allow 100 %

pacing with CRT.

(B) The patient requirees ventricular pacing or met

CRT criteria. ( level of evidence B).

New recommendation

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

CRT can be useful for patients who on GDMT

with left ventricular ejection fraction (LVEF)

less than or equal to 35% and undergoing

pacement of new or replacement of device

with anticipated more than 40 % ventricular

pacing . ( level of evidence C ).

New recommendation

I IIa IIb III

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

CRT may be considered For patients who have

left ventricular ejection fraction (LVEF) less

than or equal to 30%, ischemic HF with sinus

rhythm, LBBB and a QRS duration greater than

or equal to 150 ms NYHA Class I symptoms on

GDMT. ( level of evidence C).

New recommendation

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

CRT may be considered For patients who have

left ventricular ejection fraction (LVEF) less than or equal to

35%, sinus rhythm, non LBBB and a QRS duration 120-149 ms

and NYHA Class III/ ambulatory class IV symptoms on

GDMT. ( level of evidence B).

New recommendation

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

CRT may be considered For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, sinus rhythm, non LBBB and a

QRS duration equal to or more than 150 ms and NYHA Class II symptoms on GDMT. ( level of

evidence B).

New recommendation

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

CRT is not recommended for patients

with NYHA Class I , II and non LBBB with

QRS duration less than 150 ms. ( level of

evidence B).

New recommendation

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

2012 ACCF/AHA/HRS Focused

Updates of 2008 guidelines

CRT is not indicated for patients whose

comorbidities and/or frailty limit survival with good

functional capacity to less than 1 year. ( level of

evidence C).

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

CRT Implantation

General Health

Good Bad

No

CRT

Sinus

Rhythm

Non sinus

Rhythm

Basic Rhythm

QRS

Morphology

LBBB Non LBBB

QRS

Duration

ms 120 to 149

LVEF ≥ 35

%

150 ms≤ 150 ms≤

NYHA II, III,

ambulatory IV NYHA III,

ambulatory IV

Class I indication Class II a

indication

NYHA II, III,

ambulatory IV NYHA III,

ambulatory

IV

Class II a

indication

Class II b

indication

New or replacement of

device with ≤ 40%

ventricular pacing

AF

CRT indication

AV nodal

ablation or drug

guaranteed 100 %

CRT pacing

Class II b

indication

EF ≤ 30 %

IHD

NYHA I class

Class II a

indication

NYHA II

MUSTIC (NEJM 2001) Crossover CRT vs no CRT in patients with

CHF NYHA III, EF < 35%, QRS >

150 ms, LVEDD > 60 mm, NSR

58 6

Improved 6MWT < 0.001

QOL < 0.001

Hospitalization < 0.05

Peak VO2 < 0.03

MIRACLE (NEJM 2002) Parallel arms CRT vs no CRT in patients

with CHF NYHA III, EF < 35%, QRS >

130 ms, LVEDD > 55 mm, 6MWT

< 450 m, NSR

453 6 Improved 6MWT 0.005

NYHA class < 0.001

QOL = 0.001

LVEF < 0.001

Peak VO2

PATH-CHF (JACC 2002) Crossover CRT (LV or BiV) vs no CRT in

patients with CHF NYHA III-IV, EF

< 35%, QRS > 120 ms, PR > 150 ms,

NSR

41 12

Improved 6MWT =0.03

Peak VO2 0.002

QOL 0.062

NYHA class < 0.001

MIRACLE ICD (JAMA 2003) Parallel arms CRT + ICD vs CRT in patients

with CHF NYHA III, EF < 35%, QRS

> 130 ms, LVEDD > 55 mm, cardiac

arrest due to VT/VF, spontaneous VT or

inducible VT/VF, NSR

369 6 Improved NYHA class

QOL

No change

6MWT

=

MIRACLE ICD (JAMA 2003) Parallel arms CRT + ICD vs CRT in patients

with CHF NYHA III, EF < 35%, QRS

> 130 ms, LVEDD > 55 mm, cardiac

arrest due to VT/VF, spontaneous VT or

inducible VT/VF, NSR

369 6

Improved NYHA class 0.007

QOL 0.02

6MWT 0.36

CONTAK CD (JACC 2003) Crossover, parallel controlled CRT vs no

CRT in patients undergoing ICD

implantation with CHF NYHA II-IV,

EF < 35%, QRS > 120 ms, NSR,

indications for ICD implantation

490 6

Improved 6MWT = 0.043

Peak VO2 0.030

LVEF < 0.001

LV volumes 0.02

No significant change

NYHA class = 0.10

QOL = 0.40

COMPANION (NEJM 2004) Parallel arms Optimal pharmacological

therapy (OPT) vs CRT vs CRT + ICD

(CRT-D) in patients with CHF NYHA

III-IV, EF 35%, QRS > 120 ms

1520 16 Death or hospitalization for

CHF reduced by 34% in CRT,

40% in CRT-D

As compared to OPT <0.002

All cause mortality reduced by

36% in CRT-D

24% in CRT <0.001

=

PATH-CHF II (JACC 2003) Crossover CRT (LV only) vs no CRT in

patients with CHF NYHA II-IV, EF

< 30%, QRS > 120 ms, NSR, Peak

VO2 < 18 ml/min/kg

86 6

Improved 6MWT 0.021

QOL 0.015

Peak VO2 <0.001

No benefit in QRS 120–150 ms

CARE-HF (NEJM 2005) Open label, randomized Medical therapy

vs Medical therapy + CRT in patients

with CHF NYHA III-IV, EF 35%,

QRS > 120 ms with dyssynchrony ( aortic

preejection > 140 ms, interventricular

mechanical delay > 40 ms, delayed

activation of postlateral LV) QRS

> 150 ms (no dyssynchrony evidence

needed)

All cause mortality/

hospitalization reduction

by 37% in CRT < 0.001

All cause mortality reduced by

36% in CRT < 0.002

Improvement in QOL < 0.01

REVERSE [54] 2008 610 Parallel arm 12 Clinical composite score

LVESVI (mL /m2)

Time to hospitalization

hazard ratio (HR)

16% worsened

(CRT) vs.

21% (CON),

P = 0.10

18.4 with

CRT (P < 0.001)

0.47, P = 0.03

MADIT- CRT trial

Fig. 4 Improved heart failure-free survival with

cardiac

resynchronization therapy (CRT) in patients with

New

York Heart Association (NYHA) class II heart

failure (HF) in

the MADIT-CRT trial. Reprinted from the New

England

Journal of Medicine, Vol 361, Moss et al.,

Cardiac-Resynchronization

Therapy for the Prevention of Heart-Failure

Events, 1329-38, 2009, with permission [65].

Reverse Trial

RAFT Trial

Non Responder

It has been reported that 10–30% of patients

undergoing CRT either do not experience an

improvement or in fact may worsen following

implantation of a biventricular (BiV) pacing

system and therefore have been termed

‘nonresponders’.

1–3

Non Responder

Significant controversy persists, however,

regarding the definition of non-response, as

some experts would argue that evidence of

reverse remodeling (defined as a decrease in

end-systolic volume of >15%) is necessary

in order to categorize a patient as a

Responder.

Non Responder

whereas others maintain that

parameters such as functional class (New York

Heart Association (NYHA) classification), global

quality-of life-scores, and hospitalizations should

be included in defining success or failure of the

therapy.

Goals of AV Optimization

Allow adequate time for passive filling of the ventricles

Atrial diastole

Allow adequate time for a complete atrial contraction

Atrial kick a.k.a. atrial contribution to ventricular filling

Allow for ventricular contraction

Ventricular systole

When AV timing is not optimized and is too short

Ventricular filling time may be cut short

The atrial kick can be cut short

Hemodynamics can be impaired

If AV timing is too long, intrinsic and dyssynchronous ventricular activity can break through

Echo Doppler Waveform

Mitral Velocity Doppler Echo

Echo for CRT Optimization

Aortic Velocity Time Integral

(VTI) Echo Measure speed of blood flow past the aortic valve during

systole

Aortic VTI is proportional to cardiac output (CO)

Using Aortic VTI Echo, adjust the AV delay until you

find the greatest possible VTI value, which would

correspond to the greatest CO

Aortic VTI

Non-Echo Means of Timing

Optimization Impedance cardiography (IC)

Transthoracic impedance measurements calculate changes in

stroke volume

IC testing is fast (~ 15 minutes) but requires special equipment

Pulse pressure

Difference between systolic and diastolic blood pressure

For example, a patient with 120/80 mmHG blood pressure has

a pulse pressure of 40 (120 minus 80)

Patients with LV dysfunction typically have very low pulse

pressures (i.e., systolic and diastolic BP are close to the same)

Clinician finds the AV delay that corresponds to the greatest

pulse pressure (which means greatest stroke volume)

AV Delays with CRT Stimulation

If the patient has a good underlying atrial rhythm,

optimize the sensed AV delay

The patient will likely spend most time in atrial

tracking (atrial sensing with ventricular pacing)

If the patient requires a lot of atrial pacing,

optimize the paced AV delay

The patient will mostly be paced in the atrium

Most patients fall somewhere in-between

For these patients, optimize both sensed and paced

AV delays!

VV Timing Optimization

VV timing refers to the synchronization of RV and

LV contractions

Controlled by the interventricular delay

Programmable interval

Allows for simultaneous pacing (RV and LV together)

Allows for an offset (one ventricle before the other)

The goal of VV timing optimization is to get the

ventricles to contract as a unified whole