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Clinical Management of CRT Non-Responders

心臟內科葉冠宏醫師

CRT Is Highly Beneficial

Mortality HF or CVhospitalizations

Cardiac Function/ Structure QoL or NYHA

CARE-HF1,2 + + + NA

COMPANION3 + + NA NA

MIRACLE4 NA NA + +MIRACLE ICD5 NA NA NA +REVERSE6 NA +* + =RAFT7 + + NA NA

MADIT CRT8 +* + +* NA

CRT is an effective treatment for heart failure patients with:systolic dysfunction ventricular electrical conduction delays

1 Cleland J, et al. N Engl J Med. 2005;352:1539-1549.2 Cleland J, et al. Eur Heart J. 2006;27:1928-1932.3 Bristow M, et al. J Card Fail. 2000;6:276-285.4 Abraham W, et al. N Engl J Med. 2002;346:1845-1853.

5 Young J, et al. JAMA. 2003;289:2685-2694.6 Linde C, et al. JACC. 2008;52:1834-1843. 7 Tang A, et al. N Engl J Med. 2010;363:2385-2395. 8 Moss A, et al. N Engl J Med. 2009;361:1329-1338.

NA = Not powered, not collected, or not blinded for specific end point. * Post-hoc analysis.

CRT Response RatesOne-third of patients do not experience the full benefit of CRT

1 Abraham WT, et al. N Engl J Med. 2002;346:1845-1853.  4 Chung ES, et al. Circulation. 2008;117:2608-2616.2 Young JB, et al. JAMA. 2003;289:2685-2694.  5 Abraham WT, et al. Heart Rhythm. 2005;2:S65.3 Abraham WT, et al. Circulation. 2004;110:2864-2868. 6 Abraham WT, et al. Late-Breaking Clinical Trials, HRS 2010. Denver, CO.

Commonly Used Response Criteria in Publications

Echocardiographic↑ LVEF > 5 units↑ LVEF > 15% relative↓ LVESV ≥ 10%, no HF death↓ LVESV ≥ 15%LVESV < 115% of baseline↓ LVEDV > 15%↑ Stroke volume ≥ 15%

Combined↑ LVEF > 5 units or ↑ 6MWD ≥ 50m AND ↓ NYHA ≥ 1 or ↓ QOL ≥ 10

Clinical↓ NYHA ≥ 1↓ NYHA ≥ 1, no HF death↓ NYHA ≥ 1 and ↑ 6MWD ≥ 25%↓ NYHA ≥ 1 and ↑ 6MWD ≥ 25%, no HF death↑ 6MWD ≥ 10%, no HF death, no transplantTwo of the following 3: ↓ NYHA ≥ 1, ↑ 6MWD ≥ 50 m, ↓ QOL ≥ 15Clinical composite score improved

1Fornwalt BK, et al. Circ 2010;121:1985-1991.

Clinical Composite Score for CRT Response Assessment

Patient DeathHospitalization for Worsening HFCrossover due to Worsening HFWorsening NYHA ClassificationModerately or markedly worse on

Patient Global Assessment

Answer Yes to

Any

Patient classified as

worsened

Improved NYHA ClassificationModerately or markedly improved

on Patient Global Assessment

Answer Yes to

Any

Patient classified as

improved

Patient classified as unchanged1Packer, M. Jl of Card Fail 2001;7:176-82

CRT Response is Dependent on Multiple Factors

• Dyssynchrony• Transmural scar• Mitral

regurgitation

• “Fetal genes”• Calcium handling

• LBBB >> RBBB• QRS > 150 msec

• Female gender• Non-ischemic CM

Vanderheyden M, et al. JACC 2008;51

Moss AJ et. al. NEJM 2009;361

Potential Reasons for Suboptimal CRT Response

1Mullens W, et al. JACC. 2009;53:765-773.

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Approach to Improving Response to CRT

Select the appropriate

patient

Achieve a stable and

effective LV lead location

Deliver optimal therapy

Provide device diagnostic data that enhances

device and disease

management

At Every Stage of Care

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Am J Cardiol 2011;108:409–415

114 consecutive patients with CRT

Protocol-driven care vs. usual care

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uptitration of neurohormonal blockers (64%), echo-guided AV optimization (50%), heart failure education (42%), arrhythmia management (19%), and LV lead repositioning (7%).

Exercise Training After CRT Implant Results in Further Improvement

Patwala AY, et al. J Am Coll Cardiol 2009;53:2332–9

Three months after implantation, exercise group had 30 minute supervised sessions 3x per week

Percentage Change at 6 Months

Echo-guided A-V optimization

Adjusts AV intervals to produce the best LV filling

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Echo-guided V-V optimization Adjusts sequence & timing of LV & RV pacing, to make

the LV as efficient as possible, and to produce an optimal stroke volume

Either M-mode or VTI can be used for V-V optimization.

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Device – Based Optimization

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AdaptivCRT™ Algorithm

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Heart Rhythm 2011;8:1469 –1475

Every effort should be made to reduce native atrioventricularconduction with cardiac resynchronization therapy systems in an attempt to achieve biventricular pacing as close to100% as possible.

A Significant Percentage of Patients Do Not Achieve Optimal BiV Pacing %

Reasons for < 100% pacingAtrial fibrillationPVCsCompetitive AV nodal conduction

In a cohort of >80,000 patients, 40.7% exhibited less than 98% BiV pacingCheng A, et al. Circ Arrhythm Electrophysiol. 2012;5:884-888

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Long-term survival after CRT among patients with AF+AVJA is similar to that observed among patients in SR.Mortality is higher for AF patients treated with rate-slowing drugs.

J Am Coll Cardiol HF 2013;1:500–7

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Cardiac resynchronization therapy with 1 RV and 2 LV leads was safe and associated with significantly more LV reverse remodeling than conventional biventricular stimulation.

J Am Coll Cardiol 2008;51:1455–62

Experiments using a canine model of LBBB

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By increasing the number of LV pacing electrodes up to seven, LV activation time was substantially reduced. However, compared with single-site LV pacing, the LVdP/dtmax increased only if the hemodynamic benefit with single-site pacing was small.

MultiPoint™ Pacing Potential Benefits

Pacing from TWO LV sites (“Multipoint LV stimulation”) Capture a larger area Improve pattern of depolarization/repolarization Improve hemodynamics Improve resynchronization

Improve CRT response

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110 HF pts treated for 1 year, conventional CRT (STD, N=54), CRT with hemodynamic and electrical optimization of LV pacing site (OPT, N=36), optimization of LV pacing site + MPP (OPT-MPP, N=20)

2016 HRSAbstract

507 patients, Aug2013 – May 2015, 76 Italian centers

Europace, doi:10.1093/europace/euw094

Europace (2015) 17, 148–15148 European Centers

Heart Failure Management Strategies

ResponseOptimize Medical Treatment

Monitor and Optimize Device

Ongoing Patient Education

Regular Follow-up

Following a regimen for CRT management can increase the likelihood of a positive CRT response

Take Home Messages

CRT response can be affected by the patient’s disease state, device implant, device settings, medical therapy and patient compliance.

Heart failure management strategies which can enhance CRT patient care include optimizing medical treatment, monitoring and optimizing the device, educating the patient, and performing regular follow-up.

A structured evaluation of non-responders can help to document tests and interventions to determine causes for CRT non-response.

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