Management of Non Responders to

CRT – A practical guide

Dr G.Raghu Kishore

Management of CRT non responders - a

practical guide
INTRODUCTION
• Cardiac resynchronization therapy (CRT) is a non pharmacological treatment
alternative for patients with drug-refractory mild, moderate or severe heart
failure; New York Heart Association (NYHA) class I, II, III, and IV; prolonged QRS
duration; and severely depressed left ventricular ejection fraction.

• Clinical trials showed that CRT reduces HF hospitalizations, decreases

mortality, and improves the quality of life and cardiac function, described as
left ventricular reverse remodeling.

• However, the number of patients who do not respond to this therapy remains
as high as 30% to 35%.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
12 Predefined Echo Measures of Dyssynchrony
Standard Echo
– SPWMD Septal to posterior wall motion delay (≥ 130 ms)
– IVMD Interventricular mechanical delay (≥ 40 ms)
– LPEI LV pre-ejection interval (≥ 140 ms)
– LVFT/RR LV filling time as % of cardiac cycle length (R-R interval) (≤40%)
-- LLWC Left lateral wall contraction (any overlap)
Tissue Doppler Imaging
– Ts- (lateral-septal) Time Δ between basal lateral and septal peak (≥60 ms)
– Ts-SD Standard deviation of time to peak systolic velocity (≥ 32 ms)
– PVD Peak velocity difference (≥ 110 ms)
– DLC Delayed longitudinal contraction (≥ 2 segments)
– TD Maximum difference in time to peak displacement (median)
– Ts-peak Maximum Δ in time to peak systolic velocity (median)
– Ts-onset Maximum Δ in time to onset of systolic velocity (median)
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Cardiac resynchronization: proposed mechanisms. From Circulation, Yu CM, Chau E, Sanderson JE, et al, Tissue Doppler
Echocardiographic Evidence of Reverse Remodeling and Improved Synchronicity by Simultaneously Delaying Regional
Contraction After Biventricular Pacing Therapy in Heart Failure, 105(4), 444, Copyright ’ (2002), American Heart
Association.
Management of CRT non responders - a
practical guide
CRT Response
Mechanisms that lead to LV Reverse Remodeling - CRT can improve
intraventricular synchrony, atrioventricular synchrony, and
interventricular synchrony.

• Intraventricular synchrony - As a result of improved synchrony within the

LV ventricle, systole becomes more effective, and therefore LV EF, cardiac
output (CO), and other parameters of cardiac function are improved.

• Both LV end-systolic volume (LVESV) and MR (attributable to distortion of

the mitral apparatus) are reduced, lowering of the LA pressure and LVEDV.

Management of CRT non responders - a

practical guide
Atrioventricular synchrony- A second mechanism is the shortening of the isovolumic
contraction time (IVCT)after optimization of the atrioventricular (AV) delay.

• The effective diastolic filling time is increased, which in turn raises the stroke
volume. In addition, LA pressure is reduced due to decreases in presystolic MR.

Interventricular synchrony - A less important mechanism is the improvement of

interventricular synchrony between RV & LV.

• This benefit may mediate through ventricular interdependence. This results in the
gain in RV CO, thereby augmenting LV filling, and resulting in overall improved
cardiac function.

• The end effect of reverse remodeling will additionally improve cardiac synchrony
and decrease secondary MR, forming a positive feedback loop.
Management of CRT non responders - a
practical guide
Electrical Vs Mechanical Dyssynchrony

Two categories of dyssynchrony have been described: electrical and mechanical.

• With electrical dyssynchrony, there is abnormal conduction between the atria and
the ventricles, between the RV and LV, and, more importantly, within the LV.

• Mechanical dyssynchrony is caused by abnormal wall motion due to increased

cardiac workload and stress. This involves the presence of scar and many other
factors, including disruption of myocardial collagen matrix.

• Both of these mechanisms result in a negative impact on cardiac filling contractility,

and CO.

Management of CRT non responders - a

practical guide
Clinical studies: QRS width inclusion criteria

• The simplest way to measure electrical dyssynchrony is the QRS width.

• CARE-HF used echocardiographic determination to assess mechanical

dyssynchrony for patients with QRS widths between 120 ms and 150 ms.
Management of CRT non responders - a
practical guide
• A reduction in intraventricular dyssynchrony has been shown to predict CRT
response.

• QRS width has been shown to correlate well with interventricular dyssynchrony but
unfortunately has poor accuracy for detecting intraventricular dyssynchrony.

• it is estimated that only 70% of patients with left bundle branch block (LBBB) have
echocardiographic evidence of mechanical dyssynchrony.

• Yu and colleagues also demonstrated that the QRS duration may not be a reliable
predictor of mechanical dyssynchrony in HF.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Categories of CRT response definitions

Management of CRT non responders - a

practical guide
Criteria for CRT response
• Responders (combined clinical and echocardiographic):
Clinical response: Improvement in NYHA functional class (at least one
class) and increase of the 6 min walk distance ≥ 10%.
Echocardiographic response: absolute reduction in left ventricular end-
systolic diameter >15% and or improvement in LVEF >10%.

• Non-responders:
Unchanged or worsening of the clinical or echocardiographic
parameters, any hospitalization for unprovoked worsening of heart failure
or cardiac mortality due to worsening heart failure during the first 6
months after implantation

Management of CRT non responders - a

practical guide
Response to CRT

Management of CRT non responders - a

practical guide
CRT-Response in different trials

Management of CRT non responders - a

practical guide
• Clinical trials evaluating the effects of CRT have used different outcome
measures throughout time.

• Early clinical trials used clinical parameters such as NYHA functional class,
6-min walk test, and quality of life assessments. Clinical end point was the
decrease in HF hospitalizations.

• The clinical parameters are usually assessed subjectively by physicians and

may not be related to long-term mortality benefit.

• The NYHA functional class assessment seems to be a reliable measure of

functional status in patients with cardiac disease; however, its
reproducibility is not yet established.
Management of CRT non responders - a
practical guide
• Evaluating the improvement of echocardiography parameters, and assessing
LVEF and the decrease in end-diastolic and end-systolic LV volumes are
measures that are more objective and are highly correlated with long-term
mortality benefit.

• It is accepted to use 15% reduction in LVESV decrease to define responders;

however, the number of non responders may be as high as 43%.

• clinical and echocardiographic response do not always follow the same line,
eg, patients with improvement of their clinical status might not always show
significant reverse remodeling.

Management of CRT non responders - a

practical guide
CRT- Non Responders

Management of CRT non responders - a

practical guide
 Current Issues with CRT Response
• Firstly, the CRT response definition is highly dependent on the criteria used to define
the response.

• Studies have suggested that the response rate will vary from 32% to 91%, depending
on the criteria that were used.

• Thus response rates tend to be higher when clinical measures, such as subjective
measurements, are used but are much lower when remodeling or outcome
measurements are used.

• Also in clinical trials, there is no consensus on the optimal timeline to assess

response.
Management of CRT non responders - a
practical guide
Current Issues with CRT Response
• Secondly, response criteria may vary greatly among investigators.

• Symptomatic improvement does not always correlate with improvement in echo

or functional assessment parameters, and vice versa.

• Complicating factors also include the fact that acute hemodynamic or

echocardiographic parameters have not been associated consistently with long-
term clinical response.

• The best criteria to determine CRT response are unknown, and there is no true
agreed surrogate for mechanical dyssynchrony.

Management of CRT non responders - a

practical guide
Current Issues with CRT Response
• Finally, multiple different factors between individual patients can affect the
response.

• These factors include genetic and sex differences, stage and cause of congestive
HF, LV lead location, QRS morphology and width, the presence of multiple
comorbidities, LV scar in ischemic patients, and the frequency of AF and/or PVCs.

• Device management, including optimizing AV/VV intervals and programming to

ensure the greatest percentage of BiV pacing is another important consideration.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
 Agreement among the 15 response criteria was classified as
Agreement among the 15 response criteria was poor. The -axis
poor for 75% of the 105 possible comparisons. -Values are
shows the following ranges delineated by dotted lines: strong
color-coded according to the following ranges: green strong
agreement (0.75), moderate agreement (0.40.75), and poor
agreement(0.75), yellow moderate agreement (0.40.75), and
agreement (0.4). The worst agreement was between
red poor agreement (0.4).
echocardiographic (Echo) and clinical (Clin) parameters. *P
0.001 vs “Echo vs Echo” and “Clin vs Clin.” Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Response to CRT

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
CRT Response - predictors
• Newer trials have shown that women generally have higher rates of CRT response.

• Two predictors of adverse remodeling and poorer clinical outcomes are severe LV dilatation
and MR.

• Non-ischemic patients generally have better outcomes compared to ischemic patients.

• In a MADIT-CRT subgroup analysis of 213 patients who had AF, the investigators found that
CRT had less effect on outcomes in patients with AF.Patients with AF had poorer outcomes
with higher all-cause mortality.

• In a meta-analysis involving 1,164 patients with CRT and atrial fibrillation, despite overall
clinical improvement, the benefits appeared to be smaller compared to those who were in
sinus rhythm.
Management of CRT non responders - a
practical guide
CRT Response - predictors
• Recently, the MADIT-CRT trial showed that LV lead location matters. Apical
placement of the LV lead may enhance lead stability but is associated with worst
outcomes.

• In the trial, distal LV lead placement increased the risk of death and/or HF
hospitalization by a factor of 1.64 and increased the risk of mortality by 2.6.
Therefore, LV basal pacing was better.

• Other trials have shown that pacing at sites of late LV activation can also improve
outcomes.

• QRS width can be an important predictor of outcome. Patients with a wide QRS
(4150 ms) have the highest likelihood of responding to CRT.
Management of CRT non responders - a
practical guide
 CRT Response - predictors

• In COMPANION, the primary endpoint was met only when the QRS was > 148 ms. In
REVERSE, the primary endpoint was met when QRS was > 152 ms. In MADIT-CRT,
there was a 41% reduction in HF in patients with a QRS of > 150 ms.

• With respect to QRS width of 120–150 ms, the results of CARE-HF suggest that an
echo dyssynchrony evaluation can be potentially valuable. However, no reproducible
single echo dyssynchrony parameter is predictive of CRT response to date.

• Patients with LBBB tend to respond better symptomatically than those with RV paced
complexes or RBBB. Also, patients with LBBB have less chance of requiring a heart
transplant or implantation of an LV system device compared to RBBB or RV paced
patient populations
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
CRT Response Vs Non Response

Management of CRT non responders - a

practical guide
Approach to a CRT non responder

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
A step wise approach to a CRT-Non responder

• Step 1. Check the Electrocardiogram With and Without Pacing

• Step 2. Check the Device (Device Interrogation)
• Step 3. Check the Lead Position
• Step 4. Check the Mechanical Resynchronization Effect by Echocardiography
• Step 5. Check the Medication
• Step 6. Check Comorbidities

Management of CRT non responders - a

practical guide
Step 1. Check the Electrocardiogram With and Without Pacing
• The first recommended step is to perform and analyze the 12-lead
electrocardiogram (ECG), possibly with baseline ECG for direct comparison.

• If baseline ECG is not available, the acute effect of CRT on the electrical
conduction sequence during active and inactive pacing can be compared,
unless the patient is pacemaker-dependent. In pacemaker-dependent
patients, the ECG with CRT pacing should be compared to conventional right
ventricular apical pacing.

• Baseline QRS duration and morphology - If the baseline QRS duration

without pacing is less than 150 ms the patient is less likely to suffer from
mechanical dyssynchrony and therefore also less likely to respond.

Management of CRT non responders - a

practical guide
• Current guidelines recommend a relatively short QRS width of 120 ms or
above as an inclusion criterion for CRT.

• CRT is more effective in patients with broader QRS complex as they exhibit
higher degrees of dyssynchrony.

• a typical left bundle branch block (LBBB) pattern is associated with better
clinical outcome, as reported in a recently published MADIT-CRT sub-analysis.

• LBBB patients experienced more benefit in terms of reduction of HF events or

death with CRT (hazard ratio [HR]=0.047; P<.001) than non-LBBB patients (HR
= 1.24; P=.257).

Management of CRT non responders - a

practical guide
• The risk of ventricular arrhythmias or death was also significantly reduced by CRT
in defibrillator patients with LBBB, but not in non-LBBB (RBBB and intraventricular
conduction delay),

• LV reverse remodeling and the improvement in LVEF were significantly greater

among patients with LBBB compared to non-LBBB.

• The more the QRS width is reduced by CRT, the more beneficial CRT therapy is. A
recent substudy of the PROSPECT study showed that the difference in baseline vs
paced QRS width predicted clinical outcome in CRT patients.

• Reduction of QRS width by CRT is a specific but not very sensitive marker for CRT
response. Many patients with no significant changes in QRS width might still
favorably respond to CRT.
Management of CRT non responders - a
practical guide
Electrocardiography of a 45-year-old female cardiac resynchronization therapy recipient with left bundle branch block A, before
resynchronization; B, after cardiac resynchronization therapy implantation. Note the changes in leads I (new S wave) and V1
(new R wave) indicating initial activation from a left ventricular site.
Management of CRT non responders - a
practical guide
Presence of AF or VPCs
• Newly onset episodes of paroxysmal or persistent AF are associated with worse
outcome in CRT patients.AF often leads to tachycardia with loss of LV capture or
fusion/ pseudofusion beats with ineffective resynchronization.

• If rhythm control is failing with cardioversion and/or antiarrhythmic therapy, it is

crucial to control the ventricular rate in order to ensure biventricular capture

• Some patients require atrioventricular (AV) node ablation to ensure 100%

ventricular pacing and this aggressive approach has been shown to improve
exercise tolerance, LV reverse remodeling, and LVEF with a significant survival
benefit in this patient population.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
VPC - ablation

Management of CRT non responders - a

practical guide
• The role of pulmonary vein isolation (PVI) is still under debate. Some smaller studies
showed benefit of this procedure in HF patients; however, none of them was
conducted in CRT patients. Two large randomized trials, AMICA (NCT00652522) and
CASTLE-AF (NCT00643188), are currently enrolling patients to evaluate the effects of
pulmonary vein isolation in CRT recipients.

• Frequent ventricular ectopic beats, more frequently observed in patients with an

ischemic origin of the cardiomyopathy, inhibit LV pacing and reduce the efficacy of
CRT.

• Patients with a high burden of ventricular unifocal ectopic beats might be considered
for catheter ablation; however, clinical data are still limited.

Management of CRT non responders - a

practical guide
Assessment of LV capture

• After determining the underlying rate and rhythm, we need to assess LV capture.
LV non capture is a common cause of CRT non responders.

• Beats with biventricular pacing are showing frontal plane QRS axis in the right
superior quadrant and a dominant R wave in lead V1.

• If V1 has a negative QRS complex, LV loss of capture or a suboptimal LV lead

position is suspected.

• Fusion and pseudofusion beats are important to be recognized and corrected by

shortening of the AV-delay to ensure 100% ventricular pacing.

Management of CRT non responders - a

practical guide
Step 2. Check the Device (Device Interrogation)
• Device interrogation provides broad spectrum of information on the HF status of
the patient. Atrial, RV and LV sensing and pacing parameters have to be checked.

• Non capture is a common late complication of CRT and may result in no response.

• Phrenic nerve stimulation is also often observed in CRT recipients may lead to LV
lead dislocation.

• The percentage of LV pacing must be as high as 90% to ensure optimal CRT

delivery. It might be lower in case of LV lead dislocation, paroxysmal or permanent
AF , and frequent VPCs.

• Fusion and pseudofusion is often not detected by the device counter and the
percentage of LV pacing is falsely reported as being normal (ie, >90%) by the
device
Management of CRT non responders - a
practical guide
• AV-delay and ventriculo-ventricular(VV)-delay assessment and optimization is
essential in CRT non responders. It is recommended to perform AV-delay
optimization in all patients, guided either by the device or by echocardiography

• Data on VV-delay optimization and its role in CRT patients are limited and
controversial. Most studies suggest LV pre-activation or simultaneous LV-right
ventricular pacing to be optimal in CRT patients.CRT non responders should always
be assessed and optimized with regard to VV-timing.

• Heart rate variability is an effective measure representative of the severity of HF,

reflects changes in LVEF and in LV filling pattern. Improvement in heart rate
variability provides evidence of favorable CRT response.

Management of CRT non responders - a

practical guide
Step 3. Check the Lead Position
• LV lead location is probably one of the most important contributing factors for CRT
response; therefore it is crucial to assess the LV lead position in all CRT non
responders.

• Chest X-ray images (posterior-anterior and lateral projection) or fluoroscopy are

preferred to evaluate the LV lead location.

• The LAO view, representative of the short-axis view of the heart, helps to classify
the LV wall into anterior, anterolateral, lateral, posterolateral, and posterior LV lead
positions.

• The RAO view, which represents the long axis, is used to define basal, mid-
ventricular, and apical lead positions.
Management of CRT non responders - a
practical guide
CRT patient with suboptimal, mid-anterior left ventricular lead position. A, coronary sinus venogram in RAO view. B, coronary
sinus venogram in LAO view. C, final lead locations in RAO view. D, final lead locations in LAO view. Position of the right atrial
lead is at the right atrial appendage, right ventricular lead at the right ventricular apex, left ventricular lead in the mid-anterior
vein; external electrocardiogram electrodesManagement of CRT
are seen on the non
chest responders - a
wall.
practical guide
Optimal lead position
• It is generally recommended to implant the LV lead in a basal to mid-lateral or
posterolateral side-branch of the coronary sinus, if there is an eligible vein.

• Position of the anterior LV lead is associated with worse prognosis and non
response to CRT. However, a recent substudy published by Singh et al. has shown
that LV lead location defined as lateral, posterior or anterior did not influence the
clinical outcome in mild HF patients receiving CRT.

• Additionally, in this study, any apical LV lead location was associated with
significantly higher risk of HF or death when compared to basal or mid-ventricular
LV lead locations.

• Apical pacing in CRT might induce more heterogeneity in the LV activation and
more dyssynchrony, and therefore should be avoided.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Options to overcome suboptimal positioning:
– thoracoscopic placement and telescoping method of lead delivery
– identifying areas of LV scar (scar imaging),
– assessing the latest mechanical or electrical LV activation
– image guided or electro-anatomical guided lead placement
– device programming

Emerging techniques
– endocardial pacing,
– implantation of multiple LV leads,
– multisite pacing,
– leadless LV pacing and quadripolar leads.

Management of CRT non responders - a

practical guide
• If the non responder patient has a suboptimal LV lead location, a second LV lead
implantation is to be considered.

• CT scan might be a useful method to evaluate coronary sinus side-branches for the
second LV lead implantation.

• If transvenous LV lead implantation is not possible, an epicardial approach via

mini-thoracotomy might be considered.

• Advanced directional catheters and lead telescoping systems has increased the
optimal positioning of the CRT leads

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Imaging-guided lead placement
• Optimal placement was strongly associated with survival and response.

• CMRI is useful to know the anatomy of the venous system and site of
optimal lead placement

• Identifying both location and extent of transmural scar - SPECT and,

contrast MRI
– greater scar burden are less likely to show a clinical response to CRT
– patients with non-ischaemic aetiology of heart failure show greater degrees of
improvement in LVEF and reverse remodelling compared with ischemic
cardiomyopathy
Management of CRT non responders - a
practical guide
ECHO guided lead placement
- RCT enrolled 220 pts
randomized in 1:1 fashion into
Echo guided Vs non Echo guided
lead placement

- Pts in Echo guided group has

less HF hospitalizations or death
(log rank 0.03)

-Pts with lead placed at the site

of LV latest activation has 4 fold
increase in the reponse vs
routine placement

Management of CRT non responders - a

practical guide
ECHO guided lead placement

Management of CRT non responders - a

practical guide
Electroanatomical-guided placement
• QLV interval - time of onset of the QRS
complex (“Q”) on the ECG and the local
depolarization at the LV lead electrode
(“LV”) on IEGM.
• QLV is related to acute response, reverse
remodeling, and long-term outcome.
• Long QLV intervals (>95 ms) were associated
with
– increase in reverse remodeling and
quality of life.
– also result in higher maximal rate of left
ventricular pressure rise (dP/dtmax),
with a 10-ms increase in QLV leading to
a 1.7% to 2.0% increase in dP/dtmax .
Management of CRT non responders - a
J Cardiovasc Electrophysiol 2012;23:1237–45 J Cardiac EP 2014;25: 624–30.
practical guide
Management of CRT non responders - a
practical guide
 If the nonresponder
patient has a
suboptimal LV lead
location, a second LV
lead implantation is to
be considered

Management of CRT non responders - a

practical guide
Step 4. Check the Mechanical Resynchronization Effect by Echocardiography

• Echocardiographic assessment immediately after the device implantation or during the follow-up
procedures provides further information on the response and the non responders to CRT.

• The transmitral filling profile improves acutely in most patients with the initiation of CRT.
However, if it remains too short (below 40%-45% of the corresponding cycle length) or altered, it
can be optimized by changing the AV-delay of the device programming.

• If we have a non responder patient and pathologic transmitral filling parameters, AV-delay
optimization is suggested to be done with the use of echocardiography, preferably.

• Of note, optimal AV-delay changes throughout time; therefore, additional assessment of

transmitral filling pattern and AV-delay is recommended every 6 months

Management of CRT non responders - a

practical guide
Device programming
• Smart AV Delay - considers intrinsic AV intervals, intraventricular timing and LV
lead location, and
– it is designed to achieve fusion between intrinsic conduction through the
interventricular septum and paced activation of the latest activated region of
the LV

• QuickOpt - uses the duration of right atrial contraction to set AV delay

– such that ventricular contraction occurs fully after atrial depolarization and
contraction are complete, setting the paced AV delay as sensed AV delay plus
50 ms
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
• Presystolic septal flash is a
sensitive marker of dyssynchrony
and predicts a favorable response
in CRT.

• If septal flash is seen in a CRT non

responder that gives the diagnosis
of severe dyssynchrony, which
might be due to suboptimal lead
positioning or suboptimal device
settings;

• VV-optimization is recommended.
Management of CRT non responders - a
practical guide
 Optimization of VV timing

• Interventricular mechanical dyssynchrony is measured as the difference of the aortic

and pulmonary pre-ejection interval.

• Its immediate decrease shows effective resynchronization. Intraventricular

dyssynchrony can be evaluated by colorcoded tissue Doppler imaging methods,
measured as the SD of the time from the onset of QRS to peak longitudinal velocities
(Ts), in a 12-segment model.

• VV-optimization is a useful tool to correct intraventricular dyssynchrony by device

programming. As optimal VV-delay settings are highly variable in CRT patients,
echocardiography guided VV-optimization is recommended

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Step 5. Check the Medication
• Non responder patients often have inadequate medical therapy.

• Mullens et al. reported that up to 24% of patients did not take one of the indicated
HF therapy drugs.

• Drug discontinuation often occurs with worsening HF, progressive renal

dysfunction or when experiencing a side-effect.

• It is of high importance to re-initiate medical therapy and sufficiently increase the

dosage as suggested by the current guidelines.

• Patients with newly onset atrial or ventricular arrhythmias might additionally need
antiarrhythmic agents. Not only drug prescriptions, but careful evaluation of
patient compliance with regard to medication or fluid restriction is essential.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Step 6. Check Comorbidities

• Elderly patients have several comorbidities, like diabetes, ischemic heart disease,
and vascular and cerebral diseases, all leading to higher risk of all-cause mortality
and potentially attenuate the beneficial effects of CRT.

• Decreased renal function, anemia, and hypotension are associated with poor
prognosis in CRT recipients.

• Identifying and treating the precipitating factors of exacerbation of heart failure is

important before going for device diagnostics and programming.

Management of CRT non responders - a

practical guide
Emerging techniques
Quadripolar leads

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
• PNS due to LV pacing in 13% to 33% of patients during CRT with bipolar LV leads, with 10%
requiring lead revision. PNS requiring lead revision is between 0.0% to 0.3% among quadripolar
leads. (Europace 2012;15:77–82.Am Heart J 2011;161:552–7)
• Both scar tissue near the LV lead and total scar burden influence the response to CRT. Pacing in a
region of scar tissue can even deteriorate LV function. (Eur Heart J 2007; 28:33–41)

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Multipoint pacing (MPP)
• CRT non-responders might benefit from placement of an additional LV lead to achieve
multi-site LV pacing. So-called tri-ventricular pacing, may be useful, especially in those
with enlarged left ventricles and intraventricular conduction delay.

• 2012, Ginks et al. - Acute haemodynamic improvement, (change in LV dP/ dt) – in 26

% increase with standard biventricular pacing, and 47 % increase with triventricular
pacing (p=0.08 compared with LV endocardial pacing).

• TRIP-HF : 42 patients with permanent AF and a CRT indication, dual-vein LV pacing

did not improve NYHA class, 6 MWT, and QOL but did yield a significant improvement
in LVEF and LVESV at 3 months follow-up.

• TRUST CRT trial with 98 patients, showed that dual-site LV pacing significantly
increased CRT response based on the NYHA
Management class.
of CRT non responders - a
practical guide
• Restoration of intra-LV synchrony, rapid and uniform electrical activation of the LV
(ability to pace simultaneously and sequentially from multiple LV sites), thereby
improve CRT response by simultaneously recruiting a larger volume of myocardium.

• accomplished by appropriate atrioventricular (AV) timing achieving activation of the LV

from multiple widely separate sites [via intrinsic conduction, trans-septal conduction
from the RV pacing site, and activation from the LV pacing site].

• Beneficial effect of MPP is thought to depend on appropriate LV pacing vectors and on

inter-and intra-ventricular timing delays

• MSP may beneficial particularly in patients with ischaemic cardiomyopathy (myocardial

scarring), type I LV activation pattern and with narrower QRS.

Management of CRT non responders - a

practical guide
 Different Strategies For Guiding MPP Optimization
• Latest LV pacing site activated integrated
-
electrical delay measurement software (CRT Toolkit
TM St Jude Medical)
– facilitate measurement of the electrical
activation of the four LV electrodes, allowing
the earliest and latest LV pole to be identified.
• Anatomic approach in which MPP vectors were
empirically chosen to pace both with the distal and
the most proximal LV electrode.
• Pressure–volume loop to optimize MPP
– Pappone et al. found that the use of the widest
anatomically separated vectors is associated
with improved CRT response.
Management of CRT non responders - a IRON-MPP Registry
practical guide
Management of CRT non responders - a
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IRON-MPP registry

Management of CRT non responders - a

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Management of CRT non responders - a
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 LV endocardial pacing
• Endocardial pacing is at least a good alternative route
– for failed coronary sinus implantation, and
– also very useful in non-responders to standard CRT in case of suboptimal lead positioning
• Showed substantial acute haemodynamic improvement (measured by LV dP/dt max)
and long-term clinical amelioration.
• Life-long anticoagulation with coumarin derivatives is mandatory, with target INR
between 3.5 and 4.5 .
• Severely symptomatic class III or IV NYHA HF or other high surgical risk patients, as the
surgical risk probably outweighs the thromboembolic risk in these patients.
• NYHA class III or IV patients not responding to standard coronary sinus CRT, but only
after establishing potential efficacy with LV dp/dt max measurements and temporary
endocardial pacing.

Europace.
Management of CRT non responders -a 2010;12:1032–4
practical guide
• Facilitates pacing outside areas of scar/slow conduction because greater area of
the myocardium is accessible.

• early endocardial activation is a key factor

– in reducing activation times, and in reducing mechanical dyssynchrony and
improving patient response to endocardial CRT .

• Concentric remodelling are more likely to experience reduced activation times and
increased synchrony.

• Potential physiological benefits are -

– by engaging the sub-endocardial Purkinje network, reproduces the gradient of LV
contraction in systole in an endocardial to epicardial direction.
– This may result in more rapid myocardial recruitment, maximizing the contractile
response of the viable recruited myocytes.
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
 LV active fixation lead
• LV pacing lead position is often hampered by lead
instability and dislodgement (anatomical variability,
large coronary vessels).

• Effective and safe alternative to surgical epicardial

LV lead implantation, when standard passive
fixation LV lead implantation is impossible due to
lead instability, and also avoiding apical lead
position.

• Active fixation LV leads has limitations :

– Remain unstable in suitable in meso-basal target
positon,
– Fixation process requires retraction of lead which
may alter the previously evaluated threshold,
– Extraction is very challenging
Management of CRT non responders - a
practical guide
 Leadless LVEP
• WiCs-LV system

• Subcutaneous pulse generator detects the

co-implant’s right ventricular (RV) pacing
pulse

• triggering generation of an ultrasound

pulse that the LV endocardial plug
converts to a near-synchronous LV pacing
waveform.

• delay between RV and LV stimulation is

nominally 3 ms, essentially simultaneous.
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Adaptive CRT
• Device-based algorithm that :
– continuously alters device stimulation,
– LV only or synchronized with native RV activation, or BiV pacing,
– relative to measured intracardiac events,
– more likely to provide a dynamic physiologic response to maximize CRT,
– both for responders as well as for nonresponders.
• algorithm was developed to minimize RV pacing and the associated pacing-
induced dyssynchrony.
• constantly measuring intracardiac timing events and altering pacing in response to
three elements:
– intrinsic conduction,
– determination of the best pacing (LV-only or BiV), and
– optimization of AV and VV timing, in that sequence.

Management of CRT non responders - a

practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Management of CRT non responders - a
practical guide
Thank you

Management of CRT non responders - a

practical guide