CRT Long Term Follow-up how do we assess responders and End of life. Jonathan Sibley Senior Chief Cardiac Physiologist Essex Cardio Thoracic Centre

Transcription

1 CRT Long Term Follow-up how do we assess responders and End of life Jonathan Sibley Senior Chief Cardiac Physiologist Essex Cardio Thoracic Centre

2 Disclosures Member of the Medtronic Physiologist Advisory group BHRS Council member Paid Adhoc Education and training fro St Jude Medical

3 Issues with Assessing Responders 1. A lack of consensus on how to measure patient response to CRT. Symptomatic response may not necessarily reflect a better prognosis (Foley, et al., 2009) 2. No consensus on best device optimization method yet identified also make it difficult to identify a clear population of non-responders. 3.Device implant placebo effect reported to be as high as 40% (Mehra, et al., 2003)

4 Trials for CRT response RESPONSE-HF: Six-month, prospective, randomized (simultaneous biventricular (BiV) pacing vs. sequential BiV pacing) study to determine whether optimizing the interventricular (VV) delay decreases the rate of non-responders to CRT-D. Evaluated by < 10% improvement in 6-minute hall walk, and no class improvement or worsening in New York Heart Association (NYHA) scale. RETHINQ: The objective of this clinical study was to verify the safety and efficacy of cardiac resynchronization therapy in patients with an approved ICD indication, heart failure (NYHA Classification III), QRS duration < 130ms and evidence of mechanical dyssynchrony as measured by Echocardiography/tissue doppler imaging. BENEFIT: Prospective, non-randomized, 1-year study to determine if an algorithm based on results of dobutamine echocardiogram, cardiac troponin T (ctnt), B-type natriuretic peptide (BNP) and proteomic analysis pre-implant testing can predict whether patient will respond to CRT. RHYTHM-ICD: This study was designed to assess the safety and efficacy of a cardiac resynchronization device in patients who were indicated for ICD and had New York Heart Association Classification III or IV heart failure. RISK: This trial studies whether the combined use of ctnt and BNP measured at baseline and at follow-up visits predict and risk stratify HF improvement and all cause mortality in CRT-D patients.

5 Reasons for non-response Who doesn t respond what do the studies tell us? Mullens W, Grimm RA, Verga T, et al. Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program. JACC. 2009; 53(9):

6 Strategies to improve response in follow-up 1. AV Timing 2. Manage Arrhythmias 3. Treat Anaemia 4. Increase true Bi-V pacing % 5. Facilitate Optimal Heart Failure medication

7 Local study at CTC to validate methodology 1. Medical therapy optimised and titrated 2. Patient referred for CRT. If meet the criteria set by NICE plus no further option available device is implanted. Good separation of RV and LV leads anatomically but no pre-defined location. 3. Device check performed same day electronically optimise the device with device based algorithms. AV and VV delays based upon timing cycles and QRS width. 4. See patient as standard in 4-6 weeks time 5. See at device clinic 3 months review, If the patient feels better then classed as a responder. If they feel no better or worse then considered a non responder. 6. Non-responders optimised using Ritter method

8 Patients selected and descriptive statistics 6.5 month recruitment period Characteristic All patients (n = 22) Age, (years) 64 ± month data collection period 35 pts approached Gender male female NYHA II/III III 16 (73%) (86%) 30 volunteered to take part Ejection Fraction (%) 23±8 QRS duration (ms) 158±17 8 met exclusion criteria 22 sets of data Rhythm SR AF Paced Ischemic Non ischemic CRT-D CRT-P (77%)

9 Results 22 patients Mean follow up 144 ± 22 days 16 patient Responders* 6 Non responders* 27% NR *Purely defined by patients opinion on their symptoms

10 Ritter Method AV optimisation using Mitral in flow Doppler MR assessed VV Delays altered +/- measuring VTI at each setting MR assessed

11 Study Design and Methodology Observational study design All patient accepted for CRT-P or CRT-D at the CTC approached and asked if would like to volunteer Satisfy Inclusion Criteria (current guidelines + able to give IC + attend CTC) Exclusion Criteria Hospital admission requiring treatment within the studies time frame, mortality, unsuccessful implantation, device or lead complication fractured leads or displacement, recruited to another research project, unable to attend follow up clinic

12 Study Design and Methodology Two additional tests to standard care pathway (pre + post implant) Functional Assessment MLWHFQ (QuOL) Symptoms (Yes/No) Assessment of CRT Physiological Assessment LVEF MR Severity DFT LVOT VTI Baseline data collected either at pre admission or morning of implant 2 nd data collection approx. 3 months post implant at patients 2 nd device follow up.

13 Focused Echo Protocol 2 Dimensional (2D) images of the apical 4 and 2 chamber views were obtained LVEF measured using Simpson s Biplane

14 PW Doppler at the tip of the mitral leaflets used to assess the trans-mitral inflow patterns and diastolic filling times.

15 PW Doppler in the apical 5 chamber view assess LVOT VTI.

16 MR pre and post CRT Pre CRT Post CRT

17 Quality of life score Quality of Life Scores All patients in this study improved by > 15% 12 patients > 50% improvement Largest improvement 97% Individual Value Plot of QuOL pre, QuOL post 95% CI for the Mean QuOL improved by a median reduction of 22.5 points Significant at P < QuOL pre QuOL post

18 Ejection Fraction (%) LV Ejection Fraction improved Overall LVEF improved Considered clinically improved if EF improved by 5% (8) EF improved by a mean 4.1% Significant at P < patients improved by > 10% (suggested some pts super responders ) (Antonio, et al. 2009) EF improvement did not correlate well with symptomatic relief Individual Value Plot of EF pre, EF post 95% CI for the Mean EF pre EF post

19 Mitral regurgitation severity MR jet area as a percentage of LA area (%) Improvement in MR severity Clinically significant if reduced by a grade e.g. mod to mild. Visually several appeared to drop half a grade (subjective and not used) Mean reduction of 10.5%. MR jet area as a % of LA area. Overall in agreement with literature authors have expressed reduction in MR often improving with time and remodelling Acute changes may account for immediate patient symptomatic improvement (?placebo) Individual Value Plot of MR pre, MR post 95% CI for the Mean 0 MR pre MR post

20 LVOT VTI (cm) LVOT VTI Considering a marker or surrogate of CO would expect to increase and we use this value to optimise currently 2% reduction in VTI Difficult to explain why Individual Value Plot of VTI pre, VTI post 95% CI for the Mean Could be measurement error Limited by angle of incident Posture Blood pressure VTI pre VTI post

21 Summary Using symptoms alone 27% NR in agreement with research. However all improved QuOL scores? Symptoms may not be best way to assess response EF improved and MR reduced both consistent with published MCRCT

22 SonR-Sorin Auto optimises AV and VV delays using a proprietary lead with a microphone to optimise using heart sounds. For the optimal VV configuration, the optimal AV delay is determined on a weekly basis Every week, SonR tests 64 combinations for rest optimization Every week, SonR tests 5 combinations for exercise optimization Pizoceramic transducer

23 SonR- Sorin In the CLEAR study, 78% of patients in the SonR arm compared with 62% in the standard medical practice arm improved, using the primary composite endpoints of death, heart failure (HF) related hospitalizations, NYHA class and quality of life (QoL)

24 Multi Point Pacing St Jude MPP configurations statistically significantly improved hemodynamic parameters assessed with pressure-volume loop measurements as compared with conventional biventricular CRT pacing3: 18% relative improvement in LVdP/dtmax (15.9% vs. 13.5%, p <.001) 40% relative improvement in stroke work (27.2% vs. 19.4%, p =.018) 6% absolute improvement in stroke volume (10.4% vs. 4.1%, p =.003) - 153% relative change 5% absolute improvement in EF (10.5% vs. 5.3%, p =.003) 98% relative change

25 Fused LV Pacing - Medtronic AdaptivCRT Trial CRT trial Non-inferiority to Echo opt Non-Inferiority World-wide trial to compare AdaptivCRT with BiV pacing optimised by echo. comprehensive echo optimization of AV and VV delays. Echo optimization in the control arm was mandatory and was performed using a standardised protocol 522 patients were enrolled in this multi-center, prospective, randomized, double blind ID study. randomized 2:1 AdaptivCRT verses full echo optimization. Six month and twelve month follow-up. The primary end point was Packer s Clinical Composite Score at 6 months (combination of mortality, HF hospitalizations and patient symptoms). Classifies patients as improved, worsened or unchanged compared to their status pre-crt. This trial was powered to demonstrate that AdaptivCRT is safe and effective compared to echo optimization. Met primary endpoints, CRT patients with AdaptivCRT performed just as well or better as patients in the echo optimization arm. improvement in Packer Clinical Composite Score of 74% Improved for the AdaptivCRT arm is significantly higher than historical CRT trials such as MIRACLE, MIRACLE ICD, InSync III Marquis and PROSPECT.

26 The Hemodynamic Effect of Intrinsic Conduction During Left Ventricular Pacing as Compared to Biventricular Pacing Berry M. van Gelder, PhD; Frank A. Bracke, MD, PhD; Albert Meijer, MD, PhD; Nico H.J. Pijls, MD, PhD Methods In 34 patients with New York Heart Association functional class III or IV, sinus rhythm with normal atrioventricular (AV) conduction, left bundle branch block, QRS >130 ms, and optimal medical therapy, LVdP/dt max was measured invasively during LV and simultaneous BiV pacing. The AV interval was varied in four steps starting (AV1) with an AV interval 40 ms shorter than the intrinsic PQ time and decreased with 25% for each step. Results At AV1, LVdP/dt max was 996 ± 194 mm Hg/s for LV pacing and 960 ± 200 mm Hg/s for BiV pacing (p = ), with all patients showing ventricular fusion during LV pacing. At AV2, 21 patients had ventricular fusion with a LVdP/dt max of 983 ± 213 mm Hg/s and 957 ± 202 mm Hg/s for LV and BiV pacing, respectively. In the remaining 13 patients without fusion these values were 919 ± 164 mm Hg/s and 957 ± 174 mm Hg/s, respectively. The difference between LV and BiV at AV2 is significantly higher when fusion is present (p = 0.01). Conclusions The LVdP/dt max is higher in LV than in BiV pacing provided that LV pacing is associated with ventricular fusion caused by intrinsic activation. J Am Coll Cardiol. 2005;46(12): doi: /j.jacc

27 Adaptive CRT Trial 1 : Results Clinical Composite Score at 6 months Non-inferiority P < % 73% AdaptivCRT Echo control 16% 12% 14% 11% Improved Unchanged Worsened

28 Adaptive LV Pacing Analysis 2 Patients with Higher Percentage Synchronized LV Pacing in the acrt Arm had a lower rate of death and HF hospitalizations AdaptivCRT Arm Only Logrank P = 0.003

29 % Patients with 48 Hours of AT/AF AdaptivCRT AF Analysis 5 AdaptivCRT Reduced AF Risk by 46% As compared to patients receiving echo optimized CRT 50% 40% p = 0.03 HR = 0.54 ( ) 30% 20% 10% 0% Echo 16.2% 8.8% acrt Months Since Randomization Number remaining

30 Follow-up indicators red flags Rhythm control, identify and treat Afib quickly Patient Activity Heart rate variability Trans thoracic impedance measurements Remember periodic Echo may be required eg: progression of MR

31 Follow-up

32 Follow-up cont...

33 IN-TIME Study The Influence of Implant-Based Home Monitoring on the Clinical Management of Heart Failure Patients with an Impaired Left Ventricular Function The primary endpoint of IN-TIME was the modified Packer score, a clinical composite score consisting of mortality, overnight hospitalization for worsened heart failure, and NYHA class global self assessment. A secondary endpoint of the trial was all-cause total mortality.

34 Summary Ensure local care pathways maintain optimal medication for HF Manage patient, relatives and other heath care professionals expectations of CRT therapy Maximise true Bi-V capture There remains no one clear best way of optimising CRT

35 Clear policy essential

36 End of Life Management Approach the subject early in the patient pathway Discuss and manage as early as possible while the patient can be fully involved in the process MDT approach essential to best outcome, Patient G.P, Pallitive care, Cardiologist, other specialist (eg: oncology consultant, McMillan nurses) Our local policy states: ICD deactivation involves turning off the lifesaving electrical impulse or shock therapies ONLY. The basic pacemaker functions within the device remain active. Deactivation of these therapies in an ICD does not result in an instantaneous death. Temporary deactivation can be achieved by placing a magnet over a device and this may be considered in urgent circumstances or in the community setting but proper planning will help to avoid this situation.

37 Deactivation in the community? Avoids patient travelling Familiar surrounding for the patient Fits well with Primary care services Makes it easier for friends and families Hospital staff have to travel, cost, insurance. Unfamiliar surroundings where are the power supplies, access, parking, safety Takes highly skilled staff and possibly equipment away from delivering other care No MDT available