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Echocardiographic predictors of response to cardiac ... Echocardiographic predictors of response to cardiac ... Presentation Transcript

  • CARDIAC RESYNCHRONIZATION THERAPY FOR CONGESTIVE CARDIAC FAILURE
    Rachael Hatton – Cardiology meeting August 2009
  • Points for discussion
    Case studies
    Background – rationale, mechanisms of benefit, device implantation and complications
    CARE-HF, COMPANION and MIRACLE trials
    PROSPECT trial
    CRT consensus statement from the ASE 2008
    CRT in ischaemic cardiomyopathy
  • Case One
    Mr K, 57 year old man of Yugoslav background
    Presented in April with epigastric chest pain at rest, shortness of breath on exertion
    Serial troponins negative
    Background
    Marfan’s syndrome
    IHD – AMI 1990’s, Angioplasty and stent to proximal LAD in 2007
  • Case One
    Background
    Type 2 diabetes mellitus on metformin
    Exsmoker, 70 pack year history of smoking
    AF – warfarinised
    Hypertension
    TIA’s
    GORD
    Admitted with VT in 2004, ICD inserted
    Multiple presentations with angina and CCF
  • Case One
    April 2009
    Woke with pain during the night
    Crescendo type pattern for 2 weeks
    Angiogram – Diffuse disease, stent patent, RCA subtotally occluded with distal collaterals
    Aortogram – Mild AR, Non-dilated ascending aorta, severe disease of descending aorta
    Thallium scan – Mild anterior defect, increased lung uptake consistent with LVF
  • Case One
    Clinically, no convincing signs of heart failure
    History – Unclear if the main issue was exertional angina or breathlessness
    PPM reprogrammed to VVI 60
    EP review re ?upgrade to biventricular pacing
    First assessment – suitable for BiV
    After TTE reviewed – no BiV
  • Case One - TTE
  • Case One - TTE
  • Case Two
    Mr R, 75 year old man with CCF
    Background:
    Hypertension
    Type II diabetes mellitus
    IHD – 3 vessel disease, CABG 2003 (suboptimal result)
    Significant dyspnoea on exertion associated with poor heart rate response with exercise
    Dual chamber pacemaker inserted in 2004, increasing AF load noted at checks
  • Case Two
    Pacing along with medical therapy produced some improvement in symptoms, but not to the patient’s satisfaction
    2009 – Breathless, persistent chest pain mainly at night despite nocte GTN patch and daytime nicorandil
    Consideration given to BiV pacing
    TTE
  • Case Two - TTE
  • Case Two - TTE
  • Case Two - TTE
  • Case Two - TTE
  • Case Two - Outcome
    Has not had Bi V pacing upgrade
    Repeat angiogram showed patent grafts with no obvious targets for revascularization
    Sestamibi – mild distal anterior coronary flow impairment
  • Case Three – A success story
    Mr B, 73 year old man
    Transferred from Tamworth with worsening biventricular failure, ARF and deranged LFT’s
    Background:
    Ischaemiccardiomyopathy
    CVA
    CRF
    Ex-smoker
  • Case Three
    Hypotensive despite dobutamine infusion
    Bilateral crackles
    Pitting oedema to the hip
    Putting on weight despite large doses of diuretics
    TTE done on arrival and patient listed for BiV pacemaker
  • Case Three - TTE
  • Case Three - TTE
  • Case Three
    Rapid improvement in haemodynamics
    Rapid weight loss – 12kg in 4 days
    Gradual improvement in renal function and liver function tests
  • Case Three - TTE
  • Case Three - TTE
  • CRT in Heart Failure
    Simultaneous pacing of both ventricles, or of one ventricle in patients with bundle branch block
    Recommended for advanced heart failure
    NYHA III-IV
    Severe LV systolic dysfunction
    QRS duration > 120ms, particularly >150ms
  • Rationale for CRT
    Presence of a BBB or IV conduction delay can worsen heart failure
    Circulation 1989. Isolated LBBB associated with dyssynchronous contraction and lower LVEF than among normals (54 vs 62%)
    Similar findings with RBBB
  • Mechanisms of Benefit
    Improved contractile function
    CARE-HF trial – median LVEF 25% at baseline, CRT group had a 3.7% improvement at 3 months and 6.9% at 18 months. NEJM 2005.
    MIRACLE trial – 323 patients, LVEF at 0, 3 and 6 months – 3.4% improvement at 6 months. Circulation 2003.
    Myocardial efficiency improves – reduced oxygen consumption, reduced energy demands
  • Mechanisms of Benefit
    Reverse ventricular remodelling
    CARE-HF and MIRACLE trials – reductions in LVESD and LVEDD, reduced MR regurgitant jet area, LV mass
    Improved mechanical synchrony
  • Device Implantation and Complications
    Transvenous – Endocardial RV lead, coronary sinus lead
    Most common complication – Inability to successfully implant the LV lead (7%)
    Less common – phrenic nerve stimulation, infection (1%), CS trauma, PTX, tamponade (rare but catastrophic).
  • MIRACLE. Circulation 2003.
    323 patients with echos at 0, 3 and 6 months
    QRS > 130ms
    LVEF < 35%
    LVEDD > 55mm
    3 Primary end points –
    NYHA class
    QoL, Minnesota living with heart failure questionnaire
    6 minute walk test
  • MIRACLE
    Significant reductions in LVEDV (P 0.001) and LVESV (P 0.001) occurred at 3 months in the CRT group compared with the control group, and reductions in LVEDV and LVESV continued between 3 and 6 months in the CRT group
    3.6% improvement in LVEF at 6 months
    2.5sq cm reduction in MR area vs 0.5sq cm
    Improved QoL, 6 minute walk times
    Greater improvement in non-ischaemic disease
  • MIRACLE
  • COMPANION. NEJM 2004
    CRT with or without ICD
    1520 patients
    QRS>120, LVEF<35%, class III/IV
    Most also met current criteria for ICD insertion
  • COMPANION
    Primary end-point: composite of all-cause mortality and all-cause hospitalization
    Secondary end-point – all-cause mortality
  • COMPANION
    Primary end point – 56 and 56 vs 68%
    Secondary end-point – trend towards mortality benefit from ICD, not statistically significant (12 vs 19%)
    No variability in results based on baseline characteristics for the primary end point
    Male, renal dysfunction, class IV, LVEF<20% had increased risk of sudden death
  • COMPANION
  • COMPANION
  • CARE-HF trial. NEJM 2005.
    813 patients
    mean age 67
    NYHA III/IV – 94% class III, 62% non-ischaemic
    LVEF<35%
    QRS > 120, mean 160ms
    QRS 120-149 echo evidence of dyssynchrony
    LPEI >140ms
    IVMD > 40ms
    Delayed posterolateral wall motion
  • CARE-HF
    Primary end point – time to death from any cause or unplanned hospitalization for a major cardiovascular event
    Major secondary end point – death from any cause
  • CARE-HF
    Reduction in the primary end-point (39 vs 55%), benefit increased over time
    No variation with age, sex, NYHA class, SBP, LVEF, QRS duration or HF medications
    Reduction in mortality, mainly due to reduced deaths from worsening heart failure
  • CARE-HF
  • CARE-HF
  • CARE-HF
  • Echocardiography and dyssynchrony
    2008 consensus statement from the ASE
    Overview of mechanical dyssynchrony
    3 types:
    Intraventricular
    Interventricular
    Atrioventricular
    Approach to quantifying dyssynchromy
  • M-mode
  • M-mode
    SPWMD >130ms shown in a small series of 20 patients to be 100% sensitive and 63% specific for predicting at least a 15% decrease in LVESV and improved clinical outcome
    Poorly reproducible – shown in the PROSPECT and CONTAK-CD trials
    Addition of colour to M-mode may aid in identifying the transition points
  • Tissue Doppler
    Longitudinal tissue doppler from apical windows
    Largest body of data
    2 approaches:
    Colour TD
    Pulsed TD
  • Pulsed TD
  • Other parameters
    TD longitudinal strain, strain rate, and displacement
    Strain calculated as a percentage shortening from TD velocity data
    Radial strain
    3D echo
    Interventricular dyssynchrony measured as time from onset of QRS for ejection in LVOT an RVOT with >40-50ms difference being of possible prognostic importance
  • PROSPECT
    Circulation 2008
    Significant proportion of non-responders to CRT
    Single-centre studies suggesting echo parameters of dyssynchrony may help in patient selection
    Prospective, multicentre trial examining 12 previously studied parameters of dyssynchrony
  • PROSPECT
    Patients referred for CRT according to current guidelines
    All were on medical therapy for heart failure
    53 centres in USA, Europe and Hong Kong
    Echo at 0, 3 and 6 months then 6 monthly
    Protocol for echo studies. Sent to a core laboratory in USA or Europe.
  • PROSPECT
    Response to CRT was evaluated at 6 months using a heart failure clinical composite score (CCS), and the change in LVESV
    Response was categorised as either worsened, improved or unchanged
  • PROSPECT
  • PROSPECT
  • PROSPECT
    54% had ischaemic origin of heart failure
    European patients more non-ischaemic heart failure and lower baseline LVEF (25.5 vs 32.9%)
    Significant inter-observer variability in measurements (up to 71% for SPWMD)
    Data from Siemens machines excluded because of suboptimal data quality
  • PROSPECT
    69% of patients improved, 15% unchanged, 16% worsened
    3% died, 11% hospitalised for HF at 6 month follow up
    3 of 5 non-TDI measurements and 1 of 7 TDI methods predicted response to a level of statistical significance
    (CCS end-point)
  • PROSPECT
  • PROSPECT
    Subgroup analysis showed greater CCS response in patients with non-ischaemic heart failure (75 vs 64%)
    LVEF tended to be underestimated at individual centres where mean LVEF was 23.6%
    Core laboratories measured a mean of 29.3%, 20% of patients had a LVEF >35% when measured by the core laboratory
  • PROSPECT – sensitivity and specificity
  • PROSPECT
    Echo parameters not able to predict responders to a degree that should influence clinical decision making
    Poorly reproducible
    Intra and inter-operator variability
    Different practice styles between USA and Europe
    Ideal end point is at present unclear – clinical response tends to outweigh echo response
  • PROSPECT - conclusions
    Predictors identified in small single centre studies were found to be less useful in this larger multicentre study
    Many parameters require software that is not widely available, variation in readings makes interpretation difficult
    Other than assessing LVEF, echo does not at present add to the selection of patients for CRT
  • Prospect - Conclusions
    These findings were in keeping with the recommendation from ASE:
    “…evidence from large-scale clinical trials and current practice guidelines do not include an echocardiographic Doppler dyssynchrony study for patient selection. Accordingly this writing group does not recommend that patients who meet criteria for CRT should have therapy withheld because of results of such a study”
    “We advise that the dyssynchrony reporting should not include a recommendation whether a patient should undergo CRT, as this should be clinical decision on a case-to-case basis for these borderline or challenging cases”
  • Retrospective analysis of data from the CARE-HF trial comparing ischaemicvsnonischaemic HF
    813 patients from CARE-HF and analysed according to aetiology
    Of 339 patients with IHD, 55% were assigned to CRT (186)
    Of the non-IHD patients, 47% were assigned to CRT(223)
  • CARE-HF revisited
  • CARE-HF revisited
  • CARE-HF revisited
  • CARE-HF
    “Despite smaller long-term improvements in LV function in patients with IHD, the relative benefits of CRT on morbidity and mortality are similar in patients with and without IHD. However, as patients with IHD generally have a worse prognosis, the absolute reduction in mortality tends to be greater in this group. This dissociation between improvement in LV function and reduction in mortality suggests that CRT may exert effects beyond LV remodelling, perhaps by reducing the arrhythmic substrate.
  • Conclusions
    BiV pacing is not straight forward
    Predicting who will respond is difficult and at present there is no echocardiographic standard good enough upon which to deny patients a trial of BiV pacing within the established guidelines
    Cases should be considered on an individual basis, particularly in the absence of echo features of dysynchrony
    Ongoing work in MRI, PET with regards to predicting response
    Spare a thought for our northern neighbours
  • Thankyou