Surgical Approaches to CHF: Implications of STICH and the VAD Banff 2012 3041435-1
Prognosis of Patients with LV Dysfunction and CAD Major determinants Pt with CAD Pt with LV dysfunction Severity of LV Severity of dysfunction CAD/ischemia Results of revascularization – a paradox Peri- procedural Late risk mortality 3109552-2
Randomized Trials of CABG vs Medical Therapy Obsolete – but overall conclusions are still valid Major survival benefit of CABG vs medical therapy Sicker pt Severity of LV Multivessel LMCA/ symptoms/ dysfunction disease proximal ischemia (CASS trial) LAD (ECST) (VA trial) 3109552-1 3029215-3
Survival in Patients with LV Dysfunction (CASS Randomized Trial) 1 Vessel Disease 2 Vessel Disease 3 Vessel Disease 1.0 Proportion surviving 0.8 0.6 0.4 Surgically assigned Medically assigned 0.2 P=0.45 P=0.40 P=0.0094 0.0 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 Year Passamani: NEJM, 1985 3134927-9
STICH Trial – Outcomes • 1,212 pt All Cause Mortality Probability of death • 2002-2007 1.0 from any cause Hazard ratio 0.86 0.8 • EF <0.35 95% CI 0.72-1.04 P=0.12 0.6 • CCS angina ≤2 (95%) Medical therapy 0.4 • NYHA ≤3 (97%) 0.2 CABG 0.0 0 1 2 3 4 5 6 Years since randomization CV Mortality and CHF Hospitalization Probability of death Probability of death or hospitalization 1.0 from any cause 1.0 from CV causes for CV causes Hazard ratio 0.81 Hazard ratio 0.74 0.8 0.8 Medical therapy 95% CI 0.66-1.00 95% CI 0.64-0.85 P=0.05 P<0.001 0.6 0.6 Medical therapy CABG 0.4 0.4 0.2 0.2 CABG 0.0 0.0 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years since randomization Years since randomization Velasquez: NEJM, 2011 3029215-5 3158045-9
STICH Revascularization Hypothesis Treatment Received 1,212 602 610 Randomized Randomized MED only CABG 537 555 65 55 Received Received Received MED CABG MED As treated: MED (592) vs CABG (620) 3108948-07
All-Cause Mortality – As Treated 1.0 HR 0.70 (0.58 - 0.84) P<0.001 0.8 Mortality rate 0.6 Med 0.4 CABG 0.2 0.0 0 1 2 3 4 5 6 Years from randomization NEJM 2011 3158045-13 3029215-7
Time-Varying Hazard Ratios – As Randomized Hazard ratio Time periods (95% CI) P 30 days 3.12 (1.33, 7.31) 0.009 31 - 365 days 0.90 (0.63, 1.29) 0.568 366 days - 2 years 1.00 (0.66, 1.52) 0.982 2 years 0.68 (0.52, 0.89) 0.004 0.25 0.5 1 2 4 CABG group MED group better better Rouleau (Pers comm) 3108948-05
STICH – Impact on Clinical Practice All pt with CHF should be evaluated for CAD • Lower threshold for revascularization Symptoms Extent of Good target Lack of disease vessels comorbidities • Subset analyses of high and low risk pt are ongoing • Optimal medical therapy plays an important role • Role of viability testing is unresolved 3162016-07
Viability Testing and Mortality After Treatment • 14 nonrandomized Viability Viability Present Absent studies 15 • 1998-2006 11.7 10.6 10 8.5 ‘Weighted’ average annual mortality (%) 5 3.7 Medical therapy Revascularization 0 Camici: Circ, 2008 CP1299264-1
STICH – Myocardial Viability and Survival 1.0 SPECT Hazard ratio 0.64 Probability of death 95% CI 0.48-0.86 601 pt – viability testing 0.8 P=0.003 Without viability (114 pt) 0.6 DSE 0.4 0.2 With viability (487 pt) 0.0 0 1 2 3 4 5 6 Years since randomization Bonow: NEJM, 2011 3161027-3
STICH – Myocardial Viability and Survival Subgroup No. Deaths Hazard ratio (95% CI) P Without 114 58 0.70 (0.41-1.18) 0.53 viability With 487 178 0.86 (0.64-1.16) viability 0.25 0.50 1.0 2.0 CABG Medical better therapy better Bonow: NEJM, 2011 3161027-4
“If you are not confused by this – you are not thinking clearly.” Pogo CP1216048-2
STICH Viability Study Limitations • Non-randomized – viability performed at physician discretion • Baseline differences between pt with/without viability testing • Viability testing may have influenced clinical management • Viability determined in a binary fashion “PET and CMRI” – greater accuracy • Does not distinguish between dysfunctioning viable Viability determined in a binary fashion myocardium and reversibility 3147182-1 147182-1
Role of Viability Testing in Clinical Decision Making in Pts with LV Dysfunction Not Essential Helpful • Significant angina • Severe LV dysfunction • Good distal vessels • Extensive LV remodeling • Multiple comorbidities No Q waves • ECG • Incomplete revas- Preserved voltage cularization is likely • Reasonable surgical risk 3029215-15 3157506-7
Left Ventricular Surgical Reconstruction (Dor Procedure) Rebuild Ellipse Normal Post MI Post SVR Buckberg: Heart Failure Reviews 9:255, 2004 3127162-4
LVESV and Survival After MI • 605 pts • Age <60 yr • 4-8 weeks post MI Survival Stratified by EF and ESV EF 50% EF 40-49% EF <40% 100 100 100 ESV 90 ESV 55 mL 90 Survival (%) <130 mL (n=193) 23 80 (n=53) 90 ESV 80 70 <95 mL (n=60) 16 60 70 ESV ESV 80 21 95 mL ESV <55 mL 50 130 mL (n=186) (n=60) 60 (n=53) 12 16 40 13 70 50 30 0 2 4 6 8 10 0 2 4 6 8 10 0 2 4 6 8 10 Years Years Years White HD: Circ, 1987 3029215-17 3170448-4
CABG with or without Surgical Ventricular Reconstruction – STICH Trial Death from Any Cause or Hospitalization for Cardiac Causes 1,000 pt 0.8 Probability EF 0.35 P=0.90 0.6 CABG CAD 0.4 CABG plus SVR Dominant anterior 0.2 LV dysfunction 0.0 0 1 2 3 4 5 Year since randomization CABG CABG + alone surg ventricular Death from Any Cause 0.8 reconstruction Probability P=0.98 0.6 0.4 CABG plus SVR 0.2 CABG 0.0 0 1 2 3 4 5 Jones: NEJM, 2009 Year since randomization 3026971-18
JTCVS 2009 “Statisticians can defy nature from a flawed database” “We conclude that the editorial by Buckberg et al is misleading” “We are not suggesting that some patients may not benefit from SVR; however we are stating that in the STICH study, we were unable to identify a patient population that did” 3127162-5
Extent of LVESV Reduction Following SVR 11 Published Series -60 -52 -50 -47 -45 -43 -43 -41 -39 -39 -40 -33 -30 % -30 -19 -20 -10 0 RESTORE Mickleborough Menicanti Williams Ribeiro Dzemali Cirillo Yamaguchi Dor DiDonato Jones (2004) (2004) (2007) (2007) (2006) (2009) (2004) (2005) (2008) (2010) (2010) STICH Menicanti LA & Wechsler A 3029215-20 3170448-2
San Donato, Milan Hospital Experience STICH Trial Death from any cause Death from any cause following SVR 0.7 0.7 P=0.98 P=0.024 0.6 0.6 Post-op ESVI Post-op ESVI SVR (-16) = 66 mL/m 2 Cum hazard 0.5 0.5 60 mL/m 2 Probability CABG (-5) = 78 mL/m 2 32% 0.4 0.4 30% 0.3 0.3 CABG + SVR 0.2 0.2 Post-op ESVI 0.1 0.1 CABG <60 mL/m 2 0.0 0.0 0 2 4 6 8 0 1 2 3 4 5 5 yrs Years since surgery Years since surgery Menicanti: EJHF, 2010 Adapted from NEJM 360:1705-17, 2009 3029215-21 3170448-3
Joint ESC-EACTS Guidelines on Revascularization Myocardial Revascularization in CHF Recommendations for patients with CHF and systolic LV dysfunction (EF <35%), presenting predominantly with HF symptoms (no or mild angina: CCS 1-2) Class Level LV aneurysmectomy during CABG is indicated in I B patients with a large LV aneurysm CABG should be considered in the presence of viable IIa B myocardium, irrespective of LVESV CABG with SVR may be considered in patients with IIb B scarred LAD territory 3029215-22 3170448-9
Surgical Therapies for Heart Failure Mitral valve repair with/without CorCap device • No mortality benefit • Improved remodeling • NHLBI Trial terminated (lack of enrollment) 3106652-3
Role of LV-Assist Devices Destination Bridge-to- Bridge-to- therapy transplantation recovery? Mechanisms ? Unloading Cellular, structural and alone functional recovery • Predictors • Augmentation • Molecular mechanisms Identification of new therapeutic targets Soppa and Yacoub: Perhaps the “end - stage” failing heart Curr Opin Cardiol, 2008 may not be so end-stage after all 3029215-24 3097708-5
Clinical Molecular and Genomic Changes in Response to LVAD • Improvement in myocyte contractility and resting relaxation Density of Beta-Adrenergic Receptors B max (fmol/mg) 60 • beta-adrenergic density • Changes in gene expression 40 in beta-adrenergic signaling 20 pathways 0 NF HF HF + LVAD n=5 n=65 n=30 Klotz: JACC, 2005 • Time-dependent changes in calcium handling • Changes in cytoskeletal proteins incl sarcomeric proteins • Changes in metabolism and growth-factor genes Hall: JACC, 2011 3097704-10
A. G. Rose et al: Histopathology 9:367, 1985 3029215-26 3100800-2
Extent of Fibrosis in Dilated Cardiomyopathy • CMR study Extent of LGE in LGE true Patients • 101 patients 25 Total myocardial mass (%) • Midwall-fibrosis 21.0 20 35% 15 (predictor of VT/SCD) 10 5 4.6 0.8 0 Assemull: JACC, 2006 3100028-13 3029215-27
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