[PPT] - Surgical Approaches to CHF: Implications of STICH and the VAD Banff PowerPoint Presentation

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Surgical Approaches to CHF: Implications of STICH and the VAD

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Banff 2012

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Prognosis of Patients with LV Dysfunction and CAD

Peri- procedural risk Late mortality Results of revascularization – a paradox Severity of CAD/ischemia Pt with LV dysfunction Severity of LV dysfunction Major determinants Pt with CAD

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Randomized Trials of CABG vs Medical Therapy

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Obsolete – but overall conclusions are still valid Major survival benefit of CABG vs medical therapy Sicker pt

Severity of symptoms/ ischemia (ECST) Multivessel disease LMCA/ proximal LAD (VA trial) LV dysfunction (CASS trial)

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1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7

Year

1 Vessel Disease

Survival in Patients with LV Dysfunction (CASS Randomized Trial)

Proportion surviving

Passamani: NEJM, 1985

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1.0 0.8 0.6 0.4 0.2 0.0

2 Vessel Disease 3 Vessel Disease

Surgically assigned Medically assigned P=0.45 P=0.40 P=0.0094

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0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6 0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6 0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6

Years since randomization Probability of death from any cause

CV Mortality and CHF Hospitalization

STICH Trial – Outcomes

1,212 pt
2002-2007
EF <0.35
CCS angina ≤2 (95%)
NYHA ≤3 (97%)

All Cause Mortality

Years since randomization Probability of death from CV causes Velasquez: NEJM, 2011 Years since randomization Probability of death from any cause

r hospitalization

for CV causes

Hazard ratio 0.86 95% CI 0.72-1.04 P=0.12 Medical therapy CABG Hazard ratio 0.81 95% CI 0.66-1.00 P=0.05 Medical therapy CABG Medical therapy CABG Hazard ratio 0.74 95% CI 0.64-0.85 P<0.001

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STICH Revascularization Hypothesis

Treatment Received

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As treated: MED (592) vs CABG (620)

555 55 1,212 610

Randomized MED only Randomized CABG

537 65 602

Received MED Received CABG Received MED

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0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6

Mortality rate

NEJM 2011

All-Cause Mortality – As Treated

Med CABG HR 0.70 (0.58 - 0.84) P<0.001

Years from randomization

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Time-Varying Hazard Ratios – As Randomized

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Rouleau (Pers comm)

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 better MED group better

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All pt with CHF should be evaluated for CAD

STICH – Impact on Clinical Practice

Lower threshold for revascularization

Symptoms Extent of disease Good target vessels Lack of comorbidities

Subset analyses of high and low risk pt are
ngoing
Optimal medical therapy plays an important role
Role of viability testing is unresolved

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10.6 11.7 3.7 8.5

5 10 15

14 nonrandomized

studies

1998-2006

Camici: Circ, 2008

Viability Present Medical therapy Revascularization

Viability Testing and Mortality After Treatment

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Viability Absent ‘Weighted’ average annual mortality (%)

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STICH – Myocardial Viability and Survival

Bonow: NEJM, 2011 0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6

601 pt – viability testing SPECT DSE Years since randomization Probability of death

Hazard ratio 0.64 95% CI 0.48-0.86 P=0.003

Without viability (114 pt) With viability (487 pt)

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STICH – Myocardial Viability and Survival

Bonow: NEJM, 2011

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 better Medical therapy better

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“If you are not confused by this – you are not thinking clearly.”

Pogo

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STICH Viability Study

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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 Viability determined in a binary fashion

Does not distinguish between dysfunctioning viable

myocardium and reversibility

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Role of Viability Testing in Clinical Decision Making in Pts with LV Dysfunction

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Not Essential Helpful

Significant angina
Good distal vessels
ECG
Reasonable surgical risk

No Q waves Preserved voltage

Severe LV dysfunction
Extensive LV remodeling
Multiple comorbidities
Incomplete revas-

cularization is likely

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Left Ventricular Surgical Reconstruction (Dor Procedure)

Buckberg: Heart Failure Reviews 9:255, 2004

Rebuild Ellipse

Normal Post MI Post SVR

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50 60 70 80 90 100 2 4 6 8 10 70 80 90 100 2 4 6 8 10

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Survival Stratified by EF and ESV

White HD: Circ, 1987

Years Survival (%)

LVESV and Survival After MI

605 pts
Age <60 yr
4-8 weeks post MI

Years Years

30 40 50 60 70 80 90 100 2 4 6 8 10

EF 50% EF 40-49% EF <40%

ESV 55 mL (n=193) ESV <55 mL (n=186) ESV <95 mL (n=60) ESV 95 mL (n=60) ESV <130 mL (n=53) ESV 130 mL (n=53)

13 23

12 21

16 16

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CABG + surg ventricular reconstruction

0.0 0.2 0.4 0.6 0.8 1 2 3 4 5

Year since randomization

Death from Any Cause or Hospitalization for Cardiac Causes

Jones: NEJM, 2009

CABG with or without Surgical Ventricular Reconstruction – STICH Trial

Death from Any Cause

P=0.98

1,000 pt EF 0.35 CAD Dominant anterior LV dysfunction CABG alone Probability

0.0 0.2 0.4 0.6 0.8 1 2 3 4 5

Probability

P=0.90

Year since randomization

CABG CABG plus SVR CABG CABG plus SVR

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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”

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Menicanti LA & Wechsler A

30
33
39
43
43
39
47
52
45
41
19
60
50
40
30
20
10

%

RESTORE (2004) 3170448-2

Extent of LVESV Reduction Following SVR

11 Published Series

Mickleborough (2004) Menicanti (2007) Williams (2007) Ribeiro (2006) Dzemali (2009) Cirillo (2004) Yamaguchi (2005) Dor (2008) DiDonato (2010) Jones (2010) STICH

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0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 2 4 6 8 Menicanti: EJHF, 2010

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Death from any cause following SVR

San Donato, Milan Hospital Experience STICH Trial

Adapted from NEJM 360:1705-17, 2009

Death from any cause

Years since surgery Probability Cum hazard

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 1 2 3 4 5

Years since surgery

Post-op ESVI 60 mL/m2

Post-op ESVI <60 mL/m2

30% P=0.024

5 yrs

32%

CABG CABG + SVR

P=0.98

Post-op ESVI SVR (-16) = 66 mL/m2 CABG (-5) = 78 mL/m2

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Joint ESC-EACTS Guidelines

n Revascularization

Myocardial Revascularization in CHF

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Recommendations for patients with CHF and systolic LV dysfunction (EF <35%), presenting predominantly with HF symptoms (no or mild angina: CCS 1-2)

CABG should be considered in the presence of viable myocardium, irrespective of LVESV IIa B CABG with SVR may be considered in patients with scarred LAD territory IIb B Class Level LV aneurysmectomy during CABG is indicated in patients with a large LV aneurysm I B

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Surgical Therapies for Heart Failure

Mitral valve repair with/without CorCap device

No mortality benefit
Improved remodeling
NHLBI Trial terminated (lack of enrollment)

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Role of LV-Assist Devices

Soppa and Yacoub: Curr Opin Cardiol, 2008

Destination therapy Bridge-to- transplantation Bridge-to- recovery? Mechanisms ? Unloading alone Cellular, structural and functional recovery

Predictors
Augmentation
Molecular mechanisms

Identification of new therapeutic targets Perhaps the “end-stage” failing heart may not be so end-stage after all

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Clinical Molecular and Genomic Changes in Response to LVAD

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Improvement in myocyte contractility and resting relaxation
 beta-adrenergic density
Changes in gene expression

in beta-adrenergic signaling pathways

Time-dependent changes in calcium handling
Changes in cytoskeletal proteins incl sarcomeric proteins
Changes in metabolism and growth-factor genes

Hall: JACC, 2011

20 40 60

Bmax (fmol/mg)

Klotz: JACC, 2005 NF n=5

Density of Beta-Adrenergic Receptors

HF n=65 HF + LVAD n=30

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A. G. Rose et al: Histopathology 9:367, 1985

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Extent of Fibrosis in Dilated Cardiomyopathy

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Assemull: JACC, 2006

CMR study
101 patients
Midwall-fibrosis

0.8 4.6 21.0

5 10 15 20 25

Extent of LGE in LGE true Patients

35% (predictor of VT/SCD)

Total myocardial mass (%)

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Unravelling the molecular web

Sarcomere
Signaling
Calcium transport
Energetics

Contraction Relaxation

The Evolution of Therapy for CHF ?

Improving hemodynamics Neurohormonal inhibition

CPAP?
ICD
CRT
Ventricular assist devices
Cardiac transplantation

Non-pharmacologic therapies

Cell repair and

gene therapy

Surgical approaches
Biomarker and

hemodynamic monitoring

Present Future

Pharmacogenomic

profiling

*ACE/ARB Beta blockers Aldosterone ant.

*Titrate to maximum tolerated dose

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“Tai Chi exercise may improve quality of life, mood and exercise self-efficacy in patients with HF” Conclusion

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2004 World Bank – The World’s Top 20 Most Polluted Cities China – 12 Egypt – 1 India – 5 Thailand – 1 Indonesia – 1

“This body of evidence has grown and been strengthened substantially since the first American Heart Association Statement was published.”

Brook: Circ, 2010

Circulation, 2004

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Viability Imaging

ACC/AHA Heart Failure Guideline 2009

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Noninvasive imaging to detect myocardial ischemia and viability is reasonable in patients presenting with HF who have known coronary artery disease and no angina unless the patient is not eligible for revascularization of any kind

I IIa IIb III

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Coronary Anatomy by Treatment for 1,000 Patients (CABG vs CABG + SVR)

Major coronary arteries with stenosis Stenosis (%) CABG (%) (n=499) CABG + SVR (%) (n=501)

*0 = coronary angiogram shows no coronary disease, 100 = 95% LM stenosis

1 50 7 10 LM stenosis 50-74 14 12 1 75 17 20 2 75 41 42 3 75 41 36 Proximal LAD 75 78 74 LM stenosis 75 6 7 Duke coronary Median 65 65 disease index* (25th, 75th) (43, 91) (39, 91)

Jones: NEJM, 2009

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In conclusion, repeated sauna therapy in patients with chronic heart failure improves exercise tolerance in association with improvement in endothelial function

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