crt non responders - a practical guide

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 treatmentalternative for patients with drug-refractory mild, moderate or severe heartfailure; New York Heart Association (NYHA) class I, II, III, and IV; prolonged QRSduration; and severely depressed left ventricular ejection fraction.

• Clinical trials showed that CRT reduces HF hospitalizations, decreasesmortality, and improves the quality of life and cardiac function, described asleft ventricular reverse remodeling.

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


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

Cardiac resynchronization: proposed mechanisms. From Circulation, Yu CM, Chau E, Sanderson JE, et al, Tissue DopplerEchocardiographic Evidence of Reverse Remodeling and Improved Synchronicity by Simultaneously Delaying RegionalContraction After Biventricular Pacing Therapy in Heart Failure, 105(4), 444, Copyright ’ (2002), American HeartAssociation.


CRT Response

Mechanisms that lead to LV Reverse Remodeling - CRT can improveintraventricular synchrony, atrioventricular synchrony, andinterventricular synchrony.

• Intraventricular synchrony - As a result of improved synchrony within theLV ventricle, systole becomes more effective, and therefore LV EF, cardiacoutput (CO), and other parameters of cardiac function are improved.

• Both LV end-systolic volume (LVESV) and MR (attributable to distortion ofthe mitral apparatus) are reduced, lowering of the LA pressure and LVEDV.


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

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

Interventricular synchrony - A less important mechanism is the improvement ofinterventricular synchrony between RV & LV.

• This benefit may mediate through ventricular interdependence. This results in thegain in RV CO, thereby augmenting LV filling, and resulting in overall improvedcardiac function.

• The end effect of reverse remodeling will additionally improve cardiac synchronyand decrease secondary MR, forming a positive feedback loop.


Electrical Vs Mechanical Dyssynchrony

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

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

• Mechanical dyssynchrony is caused by abnormal wall motion due to increasedcardiac workload and stress. This involves the presence of scar and many otherfactors, including disruption of myocardial collagen matrix.

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


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

• CARE-HF used echocardiographic determination to assess mechanicaldyssynchrony for patients with QRS widths between 120 ms and 150 ms.

Clinical studies: QRS width inclusion criteria


• A reduction in intraventricular dyssynchrony has been shown to predict CRTresponse.

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

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

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


Categories of CRT response definitions


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 failureor cardiac mortality due to worsening heart failure during the first 6months after implantation


Response to CRT


CRT-Response in different trials


• Clinical trials evaluating the effects of CRT have used different outcomemeasures 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 thedecrease in HF hospitalizations.

• The clinical parameters are usually assessed subjectively by physicians andmay not be related to long-term mortality benefit.

• The NYHA functional class assessment seems to be a reliable measure offunctional status in patients with cardiac disease; however, itsreproducibility is not yet established.


• Evaluating the improvement of echocardiography parameters, and assessingLVEF and the decrease in end-diastolic and end-systolic LV volumes aremeasures that are more objective and are highly correlated with long-termmortality 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 showsignificant reverse remodeling.


CRT- Non Responders


Current Issues with CRT Response

• Firstly, the CRT response definition is highly dependent on the criteria used to definethe response.

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

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

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



• Secondly, response criteria may vary greatly among investigators.

• Symptomatic improvement does not always correlate with improvement in echoor functional assessment parameters, and vice versa.

• Complicating factors also include the fact that acute hemodynamic orechocardiographic parameters have not been associated consistently with long-term clinical response.

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



• Finally, multiple different factors between individual patients can affect theresponse.

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

• Device management, including optimizing AV/VV intervals and programming toensure the greatest percentage of BiV pacing is another important consideration.


Agreement among the 15 response criteria was classified aspoor for 75% of the 105 possible comparisons. -Values arecolor-coded according to the following ranges: green strongagreement(0.75), yellow moderate agreement (0.40.75), andred poor agreement (0.4).

Agreement among the 15 response criteria was poor. The -axisshows the following ranges delineated by dotted lines: strongagreement (0.75), moderate agreement (0.40.75), and pooragreement (0.4). The worst agreement was betweenechocardiographic (Echo) and clinical (Clin) parameters. *P0.001 vs “Echo vs Echo” and “Clin vs Clin.” Management of CRT non responders - a

practical guide

Response to CRT


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 dilatationand 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 thatCRT had less effect on outcomes in patients with AF.Patients with AF had poorer outcomeswith higher all-cause mortality.

• In a meta-analysis involving 1,164 patients with CRT and atrial fibrillation, despite overallclinical improvement, the benefits appeared to be smaller compared to those who were insinus rhythm.



• Recently, the MADIT-CRT trial showed that LV lead location matters. Apicalplacement of the LV lead may enhance lead stability but is associated with worstoutcomes.

• In the trial, distal LV lead placement increased the risk of death and/or HFhospitalization 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 improveoutcomes.

• QRS width can be an important predictor of outcome. Patients with a wide QRS(4150 ms) have the highest likelihood of responding to CRT.



• In COMPANION, the primary endpoint was met only when the QRS was > 148 ms. InREVERSE, 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 anecho dyssynchrony evaluation can be potentially valuable. However, no reproduciblesingle echo dyssynchrony parameter is predictive of CRT response to date.

• Patients with LBBB tend to respond better symptomatically than those with RV pacedcomplexes or RBBB. Also, patients with LBBB have less chance of requiring a hearttransplant or implantation of an LV system device compared to RBBB or RV pacedpatient populations


CRT Response Vs Non Response


Approach to a CRT non responder


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


Step 1. Check the Electrocardiogram With and Without Pacing

• The first recommended step is to perform and analyze the 12-leadelectrocardiogram (ECG), possibly with baseline ECG for direct comparison.

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

• Baseline QRS duration and morphology - If the baseline QRS durationwithout pacing is less than 150 ms the patient is less likely to suffer frommechanical dyssynchrony and therefore also less likely to respond.


• Current guidelines recommend a relatively short QRS width of 120 ms orabove as an inclusion criterion for CRT.

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

• a typical left bundle branch block (LBBB) pattern is associated with betterclinical 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).


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

• LV reverse remodeling and the improvement in LVEF were significantly greateramong patients with LBBB compared to non-LBBB.

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

• Reduction of QRS width by CRT is a specific but not very sensitive marker for CRTresponse. Many patients with no significant changes in QRS width might stillfavorably respond to CRT.


Electrocardiography of a 45-year-old female cardiac resynchronization therapy recipient with left bundle branch block A, beforeresynchronization; 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.


Presence of AF or VPCs

• Newly onset episodes of paroxysmal or persistent AF are associated with worseoutcome in CRT patients.AF often leads to tachycardia with loss of LV capture orfusion/ pseudofusion beats with ineffective resynchronization.

• If rhythm control is failing with cardioversion and/or antiarrhythmic therapy, it iscrucial 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 improveexercise tolerance, LV reverse remodeling, and LVEF with a significant survivalbenefit in this patient population.


VPC - ablation


• The role of pulmonary vein isolation (PVI) is still under debate. Some smaller studiesshowed benefit of this procedure in HF patients; however, none of them wasconducted in CRT patients. Two large randomized trials, AMICA (NCT00652522) andCASTLE-AF (NCT00643188), are currently enrolling patients to evaluate the effects ofpulmonary vein isolation in CRT recipients.

• Frequent ventricular ectopic beats, more frequently observed in patients with anischemic origin of the cardiomyopathy, inhibit LV pacing and reduce the efficacy ofCRT.

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


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 rightsuperior quadrant and a dominant R wave in lead V1.

• If V1 has a negative QRS complex, LV loss of capture or a suboptimal LV leadposition is suspected.

• Fusion and pseudofusion beats are important to be recognized and corrected byshortening of the AV-delay to ensure 100% ventricular pacing.


Step 2. Check the Device (Device Interrogation)

• Device interrogation provides broad spectrum of information on the HF status ofthe 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 LVlead dislocation.

• The percentage of LV pacing must be as high as 90% to ensure optimal CRTdelivery. It might be lower in case of LV lead dislocation, paroxysmal or permanentAF , and frequent VPCs.

• Fusion and pseudofusion is often not detected by the device counter and thepercentage of LV pacing is falsely reported as being normal (ie, >90%) by thedevice


• AV-delay and ventriculo-ventricular(VV)-delay assessment and optimization isessential in CRT non responders. It is recommended to perform AV-delayoptimization in all patients, guided either by the device or by echocardiography

• Data on VV-delay optimization and its role in CRT patients are limited andcontroversial. Most studies suggest LV pre-activation or simultaneous LV-rightventricular pacing to be optimal in CRT patients.CRT non responders should alwaysbe 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 ratevariability provides evidence of favorable CRT response.


Step 3. Check the Lead Position

• LV lead location is probably one of the most important contributing factors for CRTresponse; therefore it is crucial to assess the LV lead position in all CRT nonresponders.

• Chest X-ray images (posterior-anterior and lateral projection) or fluoroscopy arepreferred to evaluate the LV lead location.

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

• The RAO view, which represents the long axis, is used to define basal, mid-ventricular, and apical lead positions.


CRT patient with suboptimal, mid-anterior left ventricular lead position. A, coronary sinus venogram in RAO view. B, coronarysinus venogram in LAO view. C, final lead locations in RAO view. D, final lead locations in LAO view. Position of the right atriallead is at the right atrial appendage, right ventricular lead at the right ventricular apex, left ventricular lead in the mid-anteriorvein; external electrocardiogram electrodes are seen on the chest wall.Management of CRT non responders - a

practical guide

Optimal lead position

• It is generally recommended to implant the LV lead in a basal to mid-lateral orposterolateral side-branch of the coronary sinus, if there is an eligible vein.

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

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

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


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.


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

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

• If transvenous LV lead implantation is not possible, an epicardial approach viamini-thoracotomy might be considered.

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


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


- RCT enrolled 220 ptsrandomized in 1:1 fashion intoEcho guided Vs non Echo guidedlead placement

- Pts in Echo guided group hasless HF hospitalizations or death(log rank 0.03)

-Pts with lead placed at the siteof LV latest activation has 4 foldincrease in the reponse vsroutine placement


ECHO guided lead placement


ECHO guided lead placement

Electroanatomical-guided placement

• QLV interval - time of onset of the QRScomplex (“Q”) on the ECG and the localdepolarization at the LV lead electrode(“LV”) on IEGM.

• QLV is related to acute response, reverseremodeling, and long-term outcome.

• Long QLV intervals (>95 ms) were associatedwith

– increase in reverse remodeling andquality of life.

– also result in higher maximal rate of leftventricular pressure rise (dP/dtmax),with a 10-ms increase in QLV leading toa 1.7% to 2.0% increase in dP/dtmax .

J Cardiovasc Electrophysiol 2012;23:1237–45 J Cardiac EP 2014;25: 624–30. Management of CRT non responders - a

practical guide

If the nonresponderpatient has asuboptimal LV leadlocation, a second LVlead implantation is tobe considered


Step 4. Check the Mechanical Resynchronization Effect by Echocardiography

• Echocardiographic assessment immediately after the device implantation or during the follow-upprocedures 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, itcan be optimized by changing the AV-delay of the device programming.

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

• Of note, optimal AV-delay changes throughout time; therefore, additional assessment oftransmitral filling pattern and AV-delay is recommended every 6 months


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


• Presystolic septal flash is asensitive marker of dyssynchronyand predicts a favorable responsein CRT.

• If septal flash is seen in a CRT nonresponder that gives the diagnosisof severe dyssynchrony, whichmight be due to suboptimal leadpositioning or suboptimal devicesettings;

• 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 aorticand pulmonary pre-ejection interval.

• Its immediate decrease shows effective resynchronization. Intraventriculardyssynchrony 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 deviceprogramming. As optimal VV-delay settings are highly variable in CRT patients,echocardiography guided VV-optimization is recommended


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 indicatedHF therapy drugs.

• Drug discontinuation often occurs with worsening HF, progressive renaldysfunction or when experiencing a side-effect.

• It is of high importance to re-initiate medical therapy and sufficiently increase thedosage as suggested by the current guidelines.

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


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 mortalityand potentially attenuate the beneficial effects of CRT.

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

• Identifying and treating the precipitating factors of exacerbation of heart failure isimportant before going for device diagnostics and programming.


Emerging techniques

Quadripolar leads


• 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 quadripolarleads. (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 aregion of scar tissue can even deteriorate LV function. (Eur Heart J 2007; 28:33–41)


Multipoint pacing (MPP)

• CRT non-responders might benefit from placement of an additional LV lead to achievemulti-site LV pacing. So-called tri-ventricular pacing, may be useful, especially in thosewith 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 triventricularpacing (p=0.08 compared with LV endocardial pacing).

• TRIP-HF : 42 patients with permanent AF and a CRT indication, dual-vein LV pacingdid not improve NYHA class, 6 MWT, and QOL but did yield a significant improvementin 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 class. Management 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), therebyimprove CRT response by simultaneously recruiting a larger volume of myocardium.

• accomplished by appropriate atrioventricular (AV) timing achieving activation of the LVfrom multiple widely separate sites [via intrinsic conduction, trans-septal conductionfrom 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 oninter-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.


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.IRON-MPP RegistryManagement of CRT non responders - a

practical guide

IRON-MPP registry


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 INRbetween 3.5 and 4.5 .

• Severely symptomatic class III or IV NYHA HF or other high surgical risk patients, as thesurgical 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. 2010;12:1032–4Management of CRT non responders - a practical guide

• Facilitates pacing outside areas of scar/slow conduction because greater area ofthe myocardium is accessible.

• early endocardial activation is a key factor

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

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

• Potential physiological benefits are -

– by engaging the sub-endocardial Purkinje network, reproduces the gradient of LVcontraction in systole in an endocardial to epicardial direction.

– This may result in more rapid myocardial recruitment, maximizing the contractileresponse of the viable recruited myocytes.


LV active fixation lead

• LV pacing lead position is often hampered by leadinstability and dislodgement (anatomical variability,large coronary vessels).

• Effective and safe alternative to surgical epicardialLV lead implantation, when standard passivefixation LV lead implantation is impossible due tolead instability, and also avoiding apical leadposition.

• 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 challengingManagement of CRT non responders - a

practical guide

Leadless LVEP

• WiCs-LV system

• Subcutaneous pulse generator detects theco-implant’s right ventricular (RV) pacingpulse

• triggering generation of an ultrasoundpulse that the LV endocardial plugconverts to a near-synchronous LV pacingwaveform.

• delay between RV and LV stimulation isnominally 3 ms, essentially simultaneous.


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.


Thank you


crt non responders - a practical guide

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