CRT INDICATION,SUITABILITY

PROGRAMMING AND FOLLOW UP

SOUMYA KANTI DUTTAIPGMER ICVS

INTRODUCTION• Cardiac resynchronization therapy (CRT) using atrio-

biventricular pacing has evolved into a useful therapeutic

option for patients with heart failure, refractory to optimal

medical therapy.

• Improvements in quality of life, morbidity, mortality, severity

of mitral regurgitation (MR) and left ventricular (LV) function

have been demonstrated in large randomized clinical

trials(MUSTIC,MIRACLE,COMPANION,CONTAK CD,CARE HF)

Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN: Department of Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. QRS duration and mortality inpatients. Am Heart J 2002, 143:1085-1091.

Non responders - 30%

• A standardized definition of benefit and quantification of benefit after CRT still lacks uniformity.

• Normal heart electrical activation occurs with in 40ms

• Electrical activation is delayed from one part to other part of heart – Dyssynchrony.

• Three types of cardiac dyssynchrony may occur: _ intraventricular– interventricular– atrioventricular (AV).

DYSYSNCHRONY

Rationale for CRT• Improved contractile function- IMPROVEMENT IN EF

– This improvement is associated with greater coordination of global contraction

• Reverse ventricular remodeling• Decrease secondary MR • The ability to tolerate more aggressive medical

therapy and neurohormonal blockade, particularly with improved tolerance of beta blockers

• Improved diastolic function • Improvement in heart rate variability (HRV)

Rationale for CRT

• CRT may confer benefits by – coordinating right ventricular and LV contraction, – synchronizing the LV segments, – prolonging the diastolic filling period with

improvements of both coronary and LV filling,– restoring atrioventricular synchrony.

The Cardiac Resynchronization–Heart Failure trial

• in the CRT compared to no CRT group• CRT can provide up to a 30% improvement in SV and a

significant reduction in MR within 3 months of initiating therapy

• LVEF - increased by 3.7 percent at three months and 6.9 percent at 18 months .

• The increase in contractile function was associated with a rise in systolic pressure of about 6 mmHg

• a reduction in plasma N-T-pro-BNP of 225 pg/mL at 3 months and 1122pg/mL at 18 months (median baseline 1800 to 1900 pg/mL).

DYSYSNCHRONYAV Dyssynchrony,

Long AV Interval

A wave fuses with E

A wave abuts

Limited net diastolic stroke volume

Decreased LV filling

A delay between atrial and

ventricular contraction

AV dyssynchrony results in

1. Reduced LV filling

2. Diastolic MR

• Interventricular dyssynchrony refers to the time delay between contraction of the right and left ventricles

• Interventricular dyssynchrony results in

DYSYSNCHRONYInterventricular Dyssynchrony,

Normally LV systole occurs earlier than RV

With LBBB RV systole will be earlier than RV

RV pressure high when LV in late diastole – IVS displaced in

to LV

Incomplete LV filling

Early septal activation

Incomplete LV emptying

• The typical pattern seen with left bundle branch block is early activation of the IVS and late activation of the posterior and lateral LV walls.

• Dyssynchrony results in

1. Inefficient LV systolic performance2. Increased wall stress3. Increased end systolic volume4. Delayed relaxation- IMPAIRED FILLING5. Mitral regurgitation

DYSYSNCHRONYIntraventricular Dyssynchrony,

Atrioventricular dyssynchrony ……

Atrioventricular dyssynchrony- is said to be present when diastolic filling period (DFP) occupies less than 40% of cardiac cycle (measured by R-R interval.

1. To obtain DFP, obtain the apical four-chamber view with mitral valve in the centre of the frame.

2. Using pulsed Doppler with the sample volume placed at the tips of mitral leaflets; obtain a spectral display of mitral inflow pattern.3. Measure the time from the onset to the end of the spectral display- this represents DFP.4. Measure the R-R interval using any two consecutive regular beats. Divide DFP with R-R interval and multiply by hundred to obtain a percentage

value .

Assessment of atrioventricular dyssynchrony using pulsed-Dopplermeasurement of mitral inflow velocity at mitral leaflet tips

Assessment of intraventricular dyssynchrony

1. M-mode measurement of septal-posterior wall motion delay

(SPWMD)

2. TDI for measurement of time to peak systolic longitudinal

velocity of various myocardial segments & time to peak systolic

longitudinal strain and strain rate of various myocardial

segments

3. Assessment of radial dyssynchrony using speckle-tracking

4. Three-dimensional echocardiographyVentricular asynchrony predicts a better outcome in patients with chronic heart failure receiving cardiac resynchronization therapy. J Am Coll Cardiol2002, 40:536-545.

M-MODE MEASUREMENT OF SPWMD

This is the simplest technique to assess the septal to

posterior wall motion delay.

1. Position the M-Mode cursor at the papillary muscle

level in either the parasternal long or short axis view.

2. Keeping the sweep speed from 50-100 mm/second,

measure the time delay from peak inward septal

motion to peak inward posterior wall motion.Cardiac resynchronization therapy and the emerging role of echocardiography; the comprehensive examination. J Am Soc 2007, 20:76-90.

M-MODE MEASUREMENT OF SPWMD ……….

• In the original experience of Pitzalis et al on 20

patients with advanced heart failure, a SPWMD

(determined in parasternal short-axis view) of >130

ms was considered pathological and SPWMD

predicted inverse LV remodeling and long-term

clinical improvement after CRT, with 100%

sensitivity, 63% specificity and 85% accuracy .Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 2002, 40:1616-1622.

COLOR TDI IMAGING, M-MODE

M-MODE MEASUREMENT OF SPWMD is quite simple and widely available but it is often quite

difficult to identify the peaks in both the walls. To overcome this shortcoming, color TDI M-mode

is now recommended as it enables the identification of the peak systole by the sharp color

transition

1. Position the M-Mode cursor at the papillary muscle level in either the parasternal long or short

axis view.

2. Keeping the sweep speed from 50-100 mm/second, select color TDI.

3. Measure the time delay from peak inward septal motion to peak inward posterior wall motion, as

indicated by the sharp color transition .

A value > 130ms signifies dyssynchrony and response to CRT with a high degree of

sensitivity.

lateral wall post-systolic displacement (LWPSD)

• A another method, reported by Sassone et al, determines lateral wall post-

systolic displacement (LWPSD), measured as the difference of intervals from

QRS onset to maximal systolic displacement of the basal LV lateral wall

(assessed by M-mode in the apical 4-chamber view) and from QRS onset to the

beginning of transmitral E velocity (assessed by pulsed Doppler of mitral inflow).

• A positive LWPSD i.e. a longer interval to maximal inward displacement

of LV lateral wall than the interval to opening of the mitral valve,

identifies a severe post-systolic contraction and has been demonstrated

to be an independent predictor of CRT response in 48 patients with

end-stage heart failure and left bundle branch block.

Sassone B, Capecchi A, Boggian G, Gabrieli L, Saccà S, Vandelli R, Petracci E, Mele D: Value of baseline left lateral wall postsystolic displacement assessed by m-mode to predict reverse remodeling by cardiac resynchronization therapy. Am J Cardiol 100(3):470-5. 2007, Aug 1; Epub 2007 Jun 15

QRS onset to maximal systolic displacement of the basal LV lateral wall (assessed by M-mode in the apical 4-chamber view)

QRS onset to the beginning of transmitralE velocity (assessed by pulsed Doppler of mitral inflow)

Minus

Methodology for measuring lateral wall post-systolic displacement (LWPSD). It is measured as the difference of the time interval from QRS onset to maximal systolic displacement of the basal LV lateral wall (assessed by M-mode in the apical 4- chamber view) (upper panel) and the time interval from QRS onset to the beginning of transmitral E velocity (assessed by pulsed Doppler of mitral inflow) (lower panel). In this example, the positive value of the difference indicates the co-existence of segmental post-systolic contraction and diastolic relaxation. (Modified from Sassone B et al, Am J Cardiol 2007;100:470–475).

TDI FOR ASSESSMENT OF INTRAVENTRICULAR DYSSYNCHRONY

• Measurement of time to peak- systolic longitudinal velocity-

• Assessment of longitudinal shortening velocities ie the

time of myocardial systolic velocities (Sm) from the apical

window with TDI has been studied extensively and several

indices proposed.

There are two approaches possible- pulsed-TDI or color-coded TDI but owing to several limitations with pulsed-TDI, color TDI is now the preferred method.

Doppler myocardial imaging to evacuate the effectiveness of pacing sites in patients receiving biventricular pacing. J Am Coll Cardiol 2002, 39:489-499.

Measurement of time to peak- systolic longitudinal velocity-

1. Obtain a noise free ECG trace and good quality 2D image from the apical window with

the LV cavity in the centre of image sector and the depth adjusted to include the

mitral annulus.

2. Activate color TDI, adjusting the sector width so as to keep the frame rate > 90

frames/second.

3. Suspend breathing if possible and acquire 3-5 beats (sinus rhythm) or more (in case of

ectopics).

4. The number of LV segments to be evaluated include mainly a 12-segment model (LV

basal and middle segments in 4-, 2- and 5-chamber views) whereas LV apical segments

are not considered reliable because of the basal apical myocardial gradient own of

Tissue Doppler.

Methodology for measuring pulsed Tissue Doppler derived time to peak Sm and time to onset Sm (left panel).In the right panel measurements of time to peak Sm (upper panel) and of time to onset Sm (lower panel) are depicted. Am=Myocardial atrial velocity, CTm = Contraction time, Em = Myocardial early diastolic velocity, RTm = Myocardial relaxationtime, Sm = Myocardial systolic velocity. Mod from Agler DA et al, J Am Soc Echocardiogr 2007;20:76–90.

time to peak- systolic longitudinal velocity

• The most widely used measurements correspond to the time interval

between the onset of ECG derived QRS and the Sm peak (= time to Sm

peak) and the time interval between the onset of QRS and the onset of Sm

(= time to Sm onset), which correspond to LV PEP.

• Intra-ventricular mechanical delay has been defined for differences of >

65 ms of time to Sm peak between LV segments.

Intra-left ventricular electromechanical asynchrony: a new independent predictor of severe cardiac events in heart failure patients. J Am Col Cardiol 2004, 43:248-256.

Tissue Synchronization Imaging (TSI)

• TSI is an implementation of Ts method.

• It displays Ts (time to Sm peak) in multiple LV segments by colour coding

wall motion green (corresponding to early systolic contraction) or red,

which corresponds to delayed contraction (sensitivity = 87%, specificity =

81% and accuracy = 84% at a cut-off value of 34.4 ms in 56 patients with

severe heart failure).

A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging. J Am Coll Cardiol 2005, 45:677-684.

Methodology for recording and measuring intra-ventricular horizontal and vertical dyssynchrony by off-line color Tissue Doppler techniques. Horizontal dyssynchrony occurs between opposite walls. Vertical dyssynchrony isbetween different segments of the same wall.

Strain……• The principal benefit of LV shear strains is amplification of the 15%

shortening of myocytes into 40% radial LV wall thickening, which

ultimately translates into a >60% change in LV ejection fraction.

• Dyssynchrony from timing of peak radial strain has been

demonstrated to be correlated with Tissue Doppler measures.

• A time difference < 130 ms between the radial strain peak of LV

posterior wall and anterior septum has shown to be highly predictive

of an improved EF during follow-up, with 89% sensitivity and 83%

specificity.

Circulation 2006, 113:960-968.

Interventricular dyssynchrony

• Inter-ventricular dyssynchrony represents the

discordance between the times of right ventricular

(RV) and LV contraction.

• Interventricular mechanical dyssynchrony is

assessed by measuring the interventricular

mechanical delay.Cardiac resynchronization therapy and the emerging role of echocardiography (Part 1): indications and results from current studies. J Am Soc Echocardiogr 2007, 20:70-75.

Interventricular dyssynchrony contd…..

• PW or CW Doppler images of aortic and pulmonary

flow velocities are currently used to measure the

inter-ventricular mechanical delay (IVMD).

• A difference of IVMD values of > 40 ms and values

of LV PEP of >140 ms are considered pathological .

Echocardiographic modeling of cardiac dyssynchrony before and during multisite stimulation: a prospective study. Pacing Clin Electrophysiol 2003, 26:137-143.

Why do we optimize CRT?

• The theory behind timing optimization is that proper CRT depends on precise timing of the ventricular contractions.

• Timing must allow for :– Adequate time for the filling of the ventricles

(i.e.diastolic optimization).– Proper contraction of the right and left ventricles

with respect to each other (i.e. systolic optimization).

Promoting CRT

• Unlike conventional pacing (where the goal is to minimize unnecessary ventricular pacing), CRT should pace both ventricles as close to 100% of the time as possible.

• Percentage of LV pacing -- as high as 90%.– optimal CRT delivery

• lower pacining %– LV lead dislocation – paroxysmal or permanent atrial fibrillation– frequent ventricular ectopic beats

Promoting CRT- MTR

• The Maximum Tracking Rate sets the highest rate at which the ventricles will be paced in response to intrinsic atrial activity.

• If the patient has high intrinsic atrial rates (>MTR) with good conduction, it is possible that the ventricle will not be paced some of the time.

• Make sure the MTR is high enough so that even in the presence of high intrinsic atrial rates, the patient is paced in the ventricle as much as possible

Promoting CRT- RRAVDAdaptive CRT

• Rate-responsive Av delay (RRAVD) is the automatic shortening of the AV delay as the patient’s heart rate increases.

• This keeps the AV delay short even during periods of rapid activity.

• Programmed ON in CRT patients.• The algorithm is automatic.• Short PR int---intrinsic RV,Paced LV.• Long PR int---start biventricular pacing.

• Conventional hysteresis encourages intrinsic activity and is incompatible with CRT.

• However, negative AV hysteresis automatically shortens the AV delay whenever an intrinsic ventricular event is sensed.

• This is the “opposite” of conventional hysteresis and works to discourage intrinsic ventricular activity.

• Program it ON.

Promoting CRT:Negative AVHysteresis

COMPANION Methodoptimising AV delay

Atrial contraction contributes 20 –30% to stroke volume at rest.

Aortic VTI Method • Objective:

– Identify the AV Delay that yields the maximum cardiac output as determined by an aortic VTI measurement

• Procedure: – Obtain continuous wave Doppler echo of aortic valve outflow

to obtain VTI measurement– Record VTI values over a range of programmed AV Delays – Program the AV Delay value that yields the maximum aortic VTI

Iterative Method• Objective: – Identify the AV Delay that maximizes LV filling using mitral velocity

echocardiographic measurements1

• Procedure – Obtain transmitral Doppler echo at a “long” programmed AV Delay

during ventricular pacing– Shorten the programmed AV Delay by 10-20 ms until the echo Doppler

A-wave becomes truncated (A wave is atrial contraction)– Lengthen the programmed AV Delay back to the value where there is no

A-wave cutoff. This timing should enable ventricular contraction to occur just at the end of atrial systole

• to maximize DFT (i.e. separation of the E- and A-waves).

• to allow complete end-diastolic filling(marked by the end of the A-wave)before the onset of LV contraction.

Ritter’s method

Diastolic mitral regurgitation (Ishikawa)method

• Aims to minimize diastolic MR.• optimal AV delay = long AV delay - duration of diastolic

MR

DYSYSNCHRONY by ECHOECHO Dyssynchrony – Trial Evidence – NARROW QRS

ECHO-CRT

• Primary composite endpoint:– Hospitalization for worsening heart failure or all cause

mortality occurred in 116 of 404 pt of CRT vs 102 of 405 control pt (28.7% vs 25.2)

– MIRACLE EF TRIAL:evaluating morbidity and mortality in heart failure with

– NYHA II/III– LVEF 36-50 – QRS <130, LBBB

ECHO-CRT

The results of the PROSPECT study indicate that no single echocardiographic measure of dyssynchrony, may be recommended to further improve patient selection among the CRT candidates.

Current clinical criteria including electrocardiogram, remain the standard for CRT patient selection

DYSYSNCHRONY by ECHO

PROSPECT(PREDICTORS OF RESPONSE TO CRT

ECHO Dyssynchrony – Trial Evidence – WIDE QRS(>120ms)

Non-echocardiographicoptimization methods

• Pulse pressure• Invasive left ventricular dP/dtmax• Impedance cardiography• Finger photoplethysmography• Expert Ease for Heart Failure algorithm(EEHF)• Intracardiac electrogram (IEGM)(QuickOpt)• Peak endocardial acceleration(PEA)

CRT IN NYHA I OR II

• REVERSE TRIAL: Randomised multicentre doubleblind trial to demonstrate ,slow progression of disease through REVERSE REMODELLING.

• MADIT CRT :Prophylactic CRT-D compared with ICD alone in LVEF <30%,QRS >130ms,Ischaemic Class I or Nonischaemic class II showed significant benefit by 41% reduction in HF events.

• MUSTIC• RAFT

In AF

V-V Timing: synchronize the RV and the LV

• The best V-V setting by measuring the RVOT and LVOT via PW Doppler

• V-V above > 40 ms is considered abnormal

How to optimize VV delay?

• Invasive left ventricular dP/dtmax• L VOT TVI/SV• Tissue Doppler synchrony• Expert Ease for Heart Failure algorithm– optimal VV delay=-0.333*(RV-LV electrical delay)-

20 ms• Unpublished acute haemodynamic data in the PATH-

CHF II studies

Timing of optimization

• best evidence-based practice is to follow the CARE-HF protocol and optimize AV delay using the iterative method at – Baseline( predischarge) – 3 months,– every 6 months thereafter.

• Routine optimization of VV delay cannot be recommended.

CONCLUSIONCRT address systolic heart failure Rectify mechanical dyssynchrony improving symptoms and reducing mortality.There are now several recognized approaches to

optimize CRT. Imaging modalities can assist with identifying the

myocardium with latest mechanical activation for targeted LV lead implantation.

Device programming can be tailored to maximize biventricular pacing and thereby its benefit.

Everything should be made as

simple as possible, but not

simpler.

—Albert Einstein

THANKS