CARDIAC RESYNCHRONIZATION THERAPY FOR CONGESTIVE CARDIAC FAILURE<br />Rachael Hatton – Cardiology meeting August 2009<br />
Points for discussion<br />Case studies<br />Background – rationale, mechanisms of benefit, device implantation and compli...
Case One<br />Mr K, 57 year old man of Yugoslav background<br />Presented in April with epigastric chest pain at rest, sho...
Case One<br />Background<br />Type 2 diabetes mellitus on metformin<br />Exsmoker, 70 pack year history of smoking<br />AF...
Case One<br />April 2009<br />Woke with pain during the night<br />Crescendo type pattern for 2 weeks<br />Angiogram – Dif...
Case One<br />Clinically, no convincing signs of heart failure<br />History – Unclear if the main issue was exertional ang...
Case One - TTE<br />
Case One - TTE<br />
Case Two<br />Mr R, 75 year old man with CCF<br />Background:<br />Hypertension<br />Type II diabetes mellitus<br />IHD – ...
Case Two<br />Pacing along with medical therapy produced some improvement in symptoms, but not to the patient’s satisfacti...
Case Two - TTE<br />
Case Two - TTE<br />
Case Two - TTE<br />
Case Two - TTE<br />
Case Two - Outcome<br />Has not had Bi V pacing upgrade<br />Repeat angiogram showed patent grafts with no obvious targets...
Case Three – A success story<br />Mr B, 73 year old man<br />Transferred from Tamworth with worsening biventricular failur...
Case Three<br />Hypotensive despite dobutamine infusion<br />Bilateral crackles<br />Pitting oedema to the hip<br />Puttin...
Case Three - TTE<br />
Case Three - TTE<br />
Case Three<br />Rapid improvement in haemodynamics<br />Rapid weight loss – 12kg in 4 days<br />Gradual improvement in ren...
Case Three - TTE<br />
Case Three - TTE<br />
CRT in Heart Failure<br />Simultaneous pacing of both ventricles, or of one ventricle in patients with bundle branch block...
Rationale for CRT<br />Presence of a BBB or IV conduction delay can worsen heart failure<br />Circulation 1989. Isolated L...
Mechanisms of Benefit<br />Improved contractile function<br />CARE-HF trial – median LVEF 25% at baseline, CRT group had a...
Mechanisms of Benefit<br />Reverse ventricular remodelling<br />CARE-HF and MIRACLE trials – reductions in LVESD and LVEDD...
Device Implantation and Complications<br />Transvenous – Endocardial RV lead, coronary sinus lead<br />Most common complic...
MIRACLE. Circulation 2003.<br />323 patients with echos at 0, 3 and 6 months<br />QRS > 130ms<br />LVEF < 35%<br />LVEDD >...
MIRACLE<br />Significant reductions in LVEDV (P 0.001) and LVESV (P 0.001) occurred at 3 months in the CRT group compared ...
MIRACLE<br />
COMPANION. NEJM 2004<br />CRT with or without ICD<br />1520 patients<br />QRS>120, LVEF<35%, class III/IV<br />Most also m...
COMPANION<br />Primary end-point: composite of all-cause mortality and all-cause hospitalization<br />Secondary end-point ...
COMPANION<br />Primary end point – 56 and 56 vs 68%<br />Secondary end-point – trend towards mortality benefit from ICD, n...
COMPANION<br />
COMPANION<br />
CARE-HF trial. NEJM 2005.<br />813 patients<br />mean age 67<br />NYHA III/IV – 94% class III, 62% non-ischaemic<br />LVEF...
CARE-HF<br />Primary end point – time to death from any cause or unplanned hospitalization for a major cardiovascular even...
CARE-HF<br />Reduction in the primary end-point (39 vs 55%), benefit increased over time<br />No variation with age, sex, ...
CARE-HF<br />
CARE-HF<br />
CARE-HF<br />
Echocardiography and dyssynchrony<br />2008 consensus statement from the ASE<br />Overview of mechanical dyssynchrony<br /...
M-mode<br />
M-mode<br />SPWMD >130ms shown in a small series of 20 patients to be 100% sensitive and 63% specific for predicting at le...
Tissue Doppler<br />Longitudinal tissue doppler from apical windows<br />Largest body of data<br />2 approaches:<br />Colo...
Pulsed TD<br />
Other parameters<br />TD longitudinal strain, strain rate, and displacement<br />Strain calculated as a percentage shorten...
PROSPECT<br />Circulation 2008<br />Significant proportion of non-responders to CRT<br />Single-centre studies suggesting ...
PROSPECT<br />Patients referred for CRT according to current guidelines<br />All were on medical therapy for heart failure...
PROSPECT<br />Response to CRT was evaluated at 6 months using a heart failure clinical composite score (CCS), and the chan...
PROSPECT<br />
PROSPECT<br />
PROSPECT<br />54% had ischaemic origin of heart failure<br />European patients more non-ischaemic heart failure and lower ...
PROSPECT<br />69% of patients improved, 15% unchanged, 16% worsened<br />3% died, 11% hospitalised for HF at 6 month follo...
PROSPECT<br />
PROSPECT<br />Subgroup analysis showed greater CCS response in patients with non-ischaemic heart failure (75 vs 64%)<br />...
PROSPECT – sensitivity and specificity<br />
PROSPECT<br />Echo parameters not able to predict responders to a degree that should influence clinical decision making<br...
PROSPECT - conclusions<br />Predictors identified in small single centre studies were found to be less useful in this larg...
Prospect - Conclusions<br />These findings were in keeping with the recommendation from ASE:<br />“…evidence from large-sc...
Retrospective analysis of data from the CARE-HF trial comparing ischaemicvsnonischaemic HF<br />813 patients from CARE-HF ...
CARE-HF revisited<br />
CARE-HF revisited<br />
CARE-HF revisited<br />
CARE-HF<br />“Despite smaller long-term improvements in LV function in patients with IHD, the relative benefits of CRT on ...
Conclusions<br />BiV pacing is not straight forward<br />Predicting who will respond is difficult and at present there is ...
Thankyou<br />
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Echocardiographic predictors of response to cardiac ...

  1. 1. CARDIAC RESYNCHRONIZATION THERAPY FOR CONGESTIVE CARDIAC FAILURE<br />Rachael Hatton – Cardiology meeting August 2009<br />
  2. 2. Points for discussion<br />Case studies<br />Background – rationale, mechanisms of benefit, device implantation and complications<br />CARE-HF, COMPANION and MIRACLE trials<br />PROSPECT trial<br />CRT consensus statement from the ASE 2008<br />CRT in ischaemic cardiomyopathy<br />
  3. 3. Case One<br />Mr K, 57 year old man of Yugoslav background<br />Presented in April with epigastric chest pain at rest, shortness of breath on exertion<br />Serial troponins negative<br />Background<br />Marfan’s syndrome<br />IHD – AMI 1990’s, Angioplasty and stent to proximal LAD in 2007<br />
  4. 4. Case One<br />Background<br />Type 2 diabetes mellitus on metformin<br />Exsmoker, 70 pack year history of smoking<br />AF – warfarinised<br />Hypertension<br />TIA’s<br />GORD<br />Admitted with VT in 2004, ICD inserted<br />Multiple presentations with angina and CCF<br />
  5. 5. Case One<br />April 2009<br />Woke with pain during the night<br />Crescendo type pattern for 2 weeks<br />Angiogram – Diffuse disease, stent patent, RCA subtotally occluded with distal collaterals<br />Aortogram – Mild AR, Non-dilated ascending aorta, severe disease of descending aorta<br />Thallium scan – Mild anterior defect, increased lung uptake consistent with LVF<br />
  6. 6. Case One<br />Clinically, no convincing signs of heart failure<br />History – Unclear if the main issue was exertional angina or breathlessness<br />PPM reprogrammed to VVI 60<br />EP review re ?upgrade to biventricular pacing<br />First assessment – suitable for BiV<br />After TTE reviewed – no BiV<br />
  7. 7. Case One - TTE<br />
  8. 8. Case One - TTE<br />
  9. 9. Case Two<br />Mr R, 75 year old man with CCF<br />Background:<br />Hypertension<br />Type II diabetes mellitus<br />IHD – 3 vessel disease, CABG 2003 (suboptimal result)<br />Significant dyspnoea on exertion associated with poor heart rate response with exercise<br />Dual chamber pacemaker inserted in 2004, increasing AF load noted at checks<br />
  10. 10. Case Two<br />Pacing along with medical therapy produced some improvement in symptoms, but not to the patient’s satisfaction<br />2009 – Breathless, persistent chest pain mainly at night despite nocte GTN patch and daytime nicorandil<br />Consideration given to BiV pacing<br />TTE<br />
  11. 11. Case Two - TTE<br />
  12. 12. Case Two - TTE<br />
  13. 13. Case Two - TTE<br />
  14. 14. Case Two - TTE<br />
  15. 15. Case Two - Outcome<br />Has not had Bi V pacing upgrade<br />Repeat angiogram showed patent grafts with no obvious targets for revascularization<br />Sestamibi – mild distal anterior coronary flow impairment<br />
  16. 16. Case Three – A success story<br />Mr B, 73 year old man<br />Transferred from Tamworth with worsening biventricular failure, ARF and deranged LFT’s<br />Background:<br />Ischaemiccardiomyopathy<br />CVA<br />CRF<br />Ex-smoker<br />
  17. 17. Case Three<br />Hypotensive despite dobutamine infusion<br />Bilateral crackles<br />Pitting oedema to the hip<br />Putting on weight despite large doses of diuretics<br />TTE done on arrival and patient listed for BiV pacemaker<br />
  18. 18. Case Three - TTE<br />
  19. 19. Case Three - TTE<br />
  20. 20. Case Three<br />Rapid improvement in haemodynamics<br />Rapid weight loss – 12kg in 4 days<br />Gradual improvement in renal function and liver function tests<br />
  21. 21. Case Three - TTE<br />
  22. 22. Case Three - TTE<br />
  23. 23.
  24. 24. CRT in Heart Failure<br />Simultaneous pacing of both ventricles, or of one ventricle in patients with bundle branch block<br />Recommended for advanced heart failure<br />NYHA III-IV<br />Severe LV systolic dysfunction<br />QRS duration > 120ms, particularly >150ms<br />
  25. 25. Rationale for CRT<br />Presence of a BBB or IV conduction delay can worsen heart failure<br />Circulation 1989. Isolated LBBB associated with dyssynchronous contraction and lower LVEF than among normals (54 vs 62%)<br />Similar findings with RBBB<br />
  26. 26. Mechanisms of Benefit<br />Improved contractile function<br />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.<br />MIRACLE trial – 323 patients, LVEF at 0, 3 and 6 months – 3.4% improvement at 6 months. Circulation 2003.<br />Myocardial efficiency improves – reduced oxygen consumption, reduced energy demands<br />
  27. 27. Mechanisms of Benefit<br />Reverse ventricular remodelling<br />CARE-HF and MIRACLE trials – reductions in LVESD and LVEDD, reduced MR regurgitant jet area, LV mass<br />Improved mechanical synchrony<br />
  28. 28. Device Implantation and Complications<br />Transvenous – Endocardial RV lead, coronary sinus lead<br />Most common complication – Inability to successfully implant the LV lead (7%)<br />Less common – phrenic nerve stimulation, infection (1%), CS trauma, PTX, tamponade (rare but catastrophic).<br />
  29. 29.
  30. 30. MIRACLE. Circulation 2003.<br />323 patients with echos at 0, 3 and 6 months<br />QRS > 130ms<br />LVEF < 35%<br />LVEDD > 55mm<br />3 Primary end points – <br />NYHA class<br />QoL, Minnesota living with heart failure questionnaire<br />6 minute walk test<br />
  31. 31. MIRACLE<br />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<br />3.6% improvement in LVEF at 6 months<br />2.5sq cm reduction in MR area vs 0.5sq cm<br />Improved QoL, 6 minute walk times<br />Greater improvement in non-ischaemic disease<br />
  32. 32. MIRACLE<br />
  33. 33. COMPANION. NEJM 2004<br />CRT with or without ICD<br />1520 patients<br />QRS>120, LVEF<35%, class III/IV<br />Most also met current criteria for ICD insertion<br />
  34. 34. COMPANION<br />Primary end-point: composite of all-cause mortality and all-cause hospitalization<br />Secondary end-point – all-cause mortality<br />
  35. 35. COMPANION<br />Primary end point – 56 and 56 vs 68%<br />Secondary end-point – trend towards mortality benefit from ICD, not statistically significant (12 vs 19%)<br />No variability in results based on baseline characteristics for the primary end point<br />Male, renal dysfunction, class IV, LVEF<20% had increased risk of sudden death<br />
  36. 36. COMPANION<br />
  37. 37. COMPANION<br />
  38. 38. CARE-HF trial. NEJM 2005.<br />813 patients<br />mean age 67<br />NYHA III/IV – 94% class III, 62% non-ischaemic<br />LVEF<35%<br />QRS > 120, mean 160ms<br />QRS 120-149 echo evidence of dyssynchrony<br />LPEI >140ms<br />IVMD > 40ms<br />Delayed posterolateral wall motion<br />
  39. 39. CARE-HF<br />Primary end point – time to death from any cause or unplanned hospitalization for a major cardiovascular event<br />Major secondary end point – death from any cause<br />
  40. 40. CARE-HF<br />Reduction in the primary end-point (39 vs 55%), benefit increased over time<br />No variation with age, sex, NYHA class, SBP, LVEF, QRS duration or HF medications<br />Reduction in mortality, mainly due to reduced deaths from worsening heart failure<br />
  41. 41. CARE-HF<br />
  42. 42. CARE-HF<br />
  43. 43. CARE-HF<br />
  44. 44. Echocardiography and dyssynchrony<br />2008 consensus statement from the ASE<br />Overview of mechanical dyssynchrony<br />3 types:<br />Intraventricular<br />Interventricular<br />Atrioventricular<br />Approach to quantifying dyssynchromy<br />
  45. 45. M-mode<br />
  46. 46. M-mode<br />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<br />Poorly reproducible – shown in the PROSPECT and CONTAK-CD trials<br />Addition of colour to M-mode may aid in identifying the transition points<br />
  47. 47. Tissue Doppler<br />Longitudinal tissue doppler from apical windows<br />Largest body of data<br />2 approaches:<br />Colour TD<br />Pulsed TD<br />
  48. 48.
  49. 49. Pulsed TD<br />
  50. 50. Other parameters<br />TD longitudinal strain, strain rate, and displacement<br />Strain calculated as a percentage shortening from TD velocity data<br />Radial strain<br />3D echo<br />Interventricular dyssynchrony measured as time from onset of QRS for ejection in LVOT an RVOT with >40-50ms difference being of possible prognostic importance<br />
  51. 51. PROSPECT<br />Circulation 2008<br />Significant proportion of non-responders to CRT<br />Single-centre studies suggesting echo parameters of dyssynchrony may help in patient selection<br />Prospective, multicentre trial examining 12 previously studied parameters of dyssynchrony<br />
  52. 52. PROSPECT<br />Patients referred for CRT according to current guidelines<br />All were on medical therapy for heart failure<br />53 centres in USA, Europe and Hong Kong<br />Echo at 0, 3 and 6 months then 6 monthly<br />Protocol for echo studies. Sent to a core laboratory in USA or Europe.<br />
  53. 53. PROSPECT<br />Response to CRT was evaluated at 6 months using a heart failure clinical composite score (CCS), and the change in LVESV<br />Response was categorised as either worsened, improved or unchanged<br />
  54. 54. PROSPECT<br />
  55. 55. PROSPECT<br />
  56. 56. PROSPECT<br />54% had ischaemic origin of heart failure<br />European patients more non-ischaemic heart failure and lower baseline LVEF (25.5 vs 32.9%)<br />Significant inter-observer variability in measurements (up to 71% for SPWMD)<br />Data from Siemens machines excluded because of suboptimal data quality<br />
  57. 57. PROSPECT<br />69% of patients improved, 15% unchanged, 16% worsened<br />3% died, 11% hospitalised for HF at 6 month follow up<br />3 of 5 non-TDI measurements and 1 of 7 TDI methods predicted response to a level of statistical significance<br />(CCS end-point)<br />
  58. 58. PROSPECT<br />
  59. 59.
  60. 60. PROSPECT<br />Subgroup analysis showed greater CCS response in patients with non-ischaemic heart failure (75 vs 64%)<br />LVEF tended to be underestimated at individual centres where mean LVEF was 23.6%<br />Core laboratories measured a mean of 29.3%, 20% of patients had a LVEF >35% when measured by the core laboratory<br />
  61. 61. PROSPECT – sensitivity and specificity<br />
  62. 62. PROSPECT<br />Echo parameters not able to predict responders to a degree that should influence clinical decision making<br />Poorly reproducible<br />Intra and inter-operator variability<br />Different practice styles between USA and Europe<br />Ideal end point is at present unclear – clinical response tends to outweigh echo response<br />
  63. 63. PROSPECT - conclusions<br />Predictors identified in small single centre studies were found to be less useful in this larger multicentre study<br />Many parameters require software that is not widely available, variation in readings makes interpretation difficult<br />Other than assessing LVEF, echo does not at present add to the selection of patients for CRT<br />
  64. 64. Prospect - Conclusions<br />These findings were in keeping with the recommendation from ASE:<br />“…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”<br />“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”<br />
  65. 65.
  66. 66. Retrospective analysis of data from the CARE-HF trial comparing ischaemicvsnonischaemic HF<br />813 patients from CARE-HF and analysed according to aetiology<br />Of 339 patients with IHD, 55% were assigned to CRT (186)<br />Of the non-IHD patients, 47% were assigned to CRT(223)<br />
  67. 67. CARE-HF revisited<br />
  68. 68. CARE-HF revisited<br />
  69. 69. CARE-HF revisited<br />
  70. 70. CARE-HF<br />“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.<br />
  71. 71. Conclusions<br />BiV pacing is not straight forward<br />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<br />Cases should be considered on an individual basis, particularly in the absence of echo features of dysynchrony<br />Ongoing work in MRI, PET with regards to predicting response<br />Spare a thought for our northern neighbours<br />
  72. 72.
  73. 73. Thankyou<br />

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