SHA24/048001

Heart Failure in the st 21 Century is advanced surgery the way forward?

Saleem Haj-Yahia

BSc MD FRCS

Consultant Cardiothoracic & Transplant Surgeon Lead Clinician for Transplantation & Mechanical Circulatory Support

Golden Jubilee National Hospital, Glasgow, UK

Disclosure ●ATH funded accommodation

●Thoratec funded travel

Definition of Heart Failure ● “A syndrome in which patients have typical symptoms & signs resulting from an abnormality of cardiac structure or function”

McMurray et al. ESC Heart Failure Guidelines 2012

Heart Failure Epidemiology ● CHF Prevalence in European populations: 0.4-2% ● Mean age: 74 years ● The prevalence increases with age

• 1% at 25-54 years • 4-5% at 65-74 years ● 50% mortality within 4 years ● 10 million CHF patients in EU countries ESC Task Force on Heart Failure 2001

CHF Treatment Timeline Pre-1980s

Non-pharmacological

Bed rest: inactivity; fluid restriction

1980s

Pharmacological and Surgical

1990s

Pharmacological

2000s

Devices

The future

Digitalis; diuretics; vasodilators; cardiac transplantation Neurohumoral drugs

CRT; ICD; LVAD Cellular / Genetic

Better LVADs, destination therapy Gene therapies; cell implantation/ regeneration

Prognosis in Severe HF

Modern management of chronic heart failure

Cardiac Transplantation ● ● ● ● ● ● ● ●

Gold standard therapy for HF 10 Years survival 50-60% 20 Years survival 25% 25 Years survival 15-20% A last resort!

Mortality of 19% at 1yr Mean survival of ~10 years Increased risk of: • Opportunistic infection • Malignancy • Renal failure • Hypertension • Coronary artery disease

MCS in Advanced Heart Failure ● Intra-aortic balloon pumps ● Short term VAD ● Long term VAD

Intra-aortic balloon pumps • Improve coronary perfusion pressure, reduce afterload • Improve cardiac output • Avoid in obese, elderly, PVD • Indications in AHF

• Bridge to decision • Before surgical correction (acute • •

MR, septal rupture) PCI/CABG for AMI Bridge to VAD/Transplantation

Intra-aortic balloon pumps vs inotropes?

Intra-aortic balloon pumps

Inotropes

Pros:

Pros:

•Improve cardiac output •Improve coronary perfusion •Improve renal perfusion •Avoid need for inotropes

•Improve cardiac output

Cons: •Sepsis •Lower limb ischaemia

Cons: •Tachycardia •Ventricular dysrhythmias •Further elevation of catecholamines •Increase SVR •(Increased mortality in chronic HF)

Indications for STVADs ● “Crash and Burn” patients moribund, critically ill, multi-organ failure, +/- sepsis, often with unknown neurological state and most likely to die within minutes to hours, could be ‘Bridged To Decision’ (BTD) with potential for :

• Recovery • Long-term VAD as a “bridge to transplantation” • Transplantation ● Post Cardiotomy cardiogenic shock (PCCS) ● Post Transplant Primary Graft Dysfunction (PGD) ● Short-term RVAD support for LVAD associated RV failure

CentriMag ST-VAD ● Levitated impeller ● Flows up to 9.9l/min ● No seals or bearings ● One moving part ● Licensed for 30 days

1st Harefield report ● 2003-2005 ● 18 pts with cardiogenic shock & MOF ● Mean support 14.2 +/-15.2 days ● Overall survival rate 33%

2nd Harefield report ● 16 BTD patients ● 11/16 (68.7%) alive

• • •

2 (12.5%) recovered with successful explantation 6 (37.5%) upgraded to long-term device 3 (18.8%) bridged to transplantation

1m 85.7%

6m 64.9%

12m 64.9%

Cambridge Experience ● 27 pts, 2004 – 2006 ● Indications • End-stage heart failure (9) • LVAD induced Right Heart Failure (5 RVAD) • Postcardiotomy (7) • Donor Graft Failure (6) ● 30% (8/27) overall survival to recovery, long-term device, transplantation ● Main causes of death - MOF, Stroke J Heart Lung Transplant 2008;27:158–64.

USA clinical experience ● Multicentre non-randomised trial ● 38 patients

• 12 postcardiotomy cardiogenic shock (PCCS) • 14 post MI cardiogenic shock (PMICS) • 12 LVAD induced RV failure ● Mean support 13 (1-60) days

John et al. JTCVS 2010

VAD vs ECMO

● 183 patients • VAD group—implantation of VAD system (n = 20); • ECMO group—implantation of ECMO system (n = 150) • ECMO-VAD group—implantation of ECMO but conversion to VAD later (n = 13)

Mortality and survival data

Artif Organs, Vol. 31, No. 5, 2007

Scottish ‘Crash and Burn’ Experience ● Jan 2010-present, 18 moribund INTERMACS I patients ● Short-term VADs used as ‘bridge to decision’ ● 10 BiVADs, 4 LVADs, 4 VAD-ECMO ● Outcomes

• 13 (72.2%) bridged to explantation, •

transplantation or LT support 5 (33.3) deaths

Myocardial recovery

22

Bridge to long-term support

â—?

23

Short-term VADs - Take home points STVADs are effective in bridging (bridge to decision) ‘crash and burn’ patients to: ●Recovery ●Longterm device ●Transplantation

Long-term VAD - Indications Symptomatic class III & IV advanced heart failure patients despite optimal medical therapy ● Destination therapy (DT) ● Bridge to transplant (BTT) ● Bridge to recovery (BTR)

First Generation LVADs PVAD

First Generation LVADs HeartMate I

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Long Term Ventricular Assist Devices Second and third generation LT-VADs

HM II

S Haj-Yahia et al. JTCVS 2007 S Haj-Yahia et al.

JTCVS 2009

S Haj-Yahia et al. JTCVS 2007

Destination therapy (DT) â—? REMATCH (HM I) trial

N Engl J Med. 2001;345(20):1435-43.

DT - HM I vs HM II Trial

Slaughter et al NEJM 2009; 361:2241-2251

Destination therapy - Summary

NEJM 2009;361(23):2241-51. NEJM 2001;345(20):1435-43.

DT - Functional Capacity (NYHA Class) •Rogers JG et al 2010 •372 DT patients, 2yr followup •Majority improving to NYHA I or II

Changes in Functional Class Following HeartMate II*

Rogers JG, Aaronson KD, Boyle AJ et al, JACC, 2010;55:1826-34.

DT - Quality of Life

Changes in Quality of Life Following HeartMate II: Kansas City Cardiomyopathy Questionnaire (KCCQ) * Rogers JG, Aaronson KD, Boyle AJ et al, JACC, 2010;55:1826-34

DT- Quality of Life

Destination therapy – Take home messages

● Continuous flow devices (HeartMate II) provide better

• • • •

Survival QOL Durability Safety profile

Bridge to transplantation (BTT) ● Cardiogenic shock and unlikely to survive to transplantation ● Miller et al 2007

• Multi-centre, non-randomised, 133 HeartMate II implantation as BTT

Miller et al NEJM 2007;357:885-96.

Miller et al, 2007

Miller et al NEJM 2007;357:885-96

HM II v HM I & IVAD (Post-Approval Study) â—? 169 consecutive HM II vs 169 other LVADs (79% HM I , 21% IVAD)

Starling et al JACC. 2011 May 10;57(19):1890-8.

BTT - Functional Capacity (NYHA) •Rogers et al •281 BTT patients •Majority improving to NYHA I or II

Changes in Functional Class Following HeartMate II* Rogers JG, Aaronson KD, Boyle AJ et al, JACC, 2010;55:1826-34.

BTT - Quality of Life

Changes in Quality of Life Following HeartMate II: Kansas City Cardiomyopathy Questionnaire (KCCQ) * Rogers JG, Aaronson KD, Boyle AJ et al, JACC, 2010;55:1826-34

BTT – Take home points ● Significant improvement in survival reaching 85% at one year ● Dramatic improvements in QoL ● HMII superior to other LVADs

‘Bridge to recovery’ (BTR) ● Unloading allows reverse remodelling, functional myocardial improvement and regression of left ventricular hypertrophy ● EJ Birks 2006 NEJM • 15 patients with severe HF due to nonischemic

• •

cardiomyopathy 14 HM I and 1 HM II implanted Pharmacotherapy regimen  

Lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling.

Clenbuterol to prevent myocardial atrophy EJ Birks NEJM 2006;355:1873-84.

‘Bridge to recovery’ (BTR) ● 11/15 sufficient recovery allowing explantation at mean (±SD) 320±186 days ● Mean LVEF 64±8% before explantation vs 12±6% before implantation (P = 0.001) ● Survival rate 1 and 4 years after explantation was 90.9% and 81.8% ● 100% free from HF at 1 years and 88.9% at 4 years ● 4/15 underwent transplantation due to lack of myocardial recovery

EJ Birks NEJM 2006;355:1873-84.

Bridge to Recovery (BTR)

Discharged to the hotel after 6 weeks of support.

Pharmacological treatment •HF medications and Clenbuterol for 7 months Full myocardial recovery

One week post HM II implant

Device selection?

â—? Which VAD for which patient?

HeartMate II - Worldwide Clinical Experience* More than 13,000 patients worldwide have now been implanted with the HeartMate II LVAS. ● ● ● ● ● ● ●

Patients supported ≥ 1 year: 3263 Patients supported ≥ 2 years: 1220 Patients supported ≥ 3 years: 436 Patients supported ≥ 4 years: 151 Patients supported ≥ 5 years: 40 Patients supported ≥ 6 years: 13 Patients supported ≥ 7 years: 1

*Based on clinical trial and device tracking data

HeartWare (HVAD)

Bridge to transplantation ADVANCE Trial

Circulation. 2012;125:3191-3200

Bridge to transplantation ADVANCE Trial

Circulation. 2012;125:3191-3200

Bridge to transplantation ADVANCE Trial - Caveats ● Not randomised ● Control group was drawn from INTERMACS registry for all BTT LVADS during study period ● Control group results were averaged and not stratified by device type ● Higher rate of INTERMACs I & II in the control group (60% vs 29%) ● Study only showed non-inferiority ● Higher stroke rate

● Followup of 180 days

Bridge to transplantation ADVANCE Trial ADVANCE trial

Vs HMII results from post-approval BTT study 2011

Bridge to transplantation ADVANCE Trial

HVAD

HVAD vs HM II

●Advantages • Small intra-pericardial pump • User friendly and easier implantation for less

•

experienced VAD surgeons More readily acceptable for minimally invasive implant/explant techniques

●Disadvantages • FDA approved only for BTT • Little worldwide experience and few publications • Higher incidence of pump thrombosis • Requires more potent anti-coagulation and strict monitoring

HVAD vs HM II HMII ●Advantages • FDA approval BTT and DT • Large worldwide clinical experience with a wealth of scientific evidence (BTT, DT, BTR) Lower stroke rate Lower anticoagulation requirements Evidence of superiority over PF devices

• • • ●Disadvantages • Larger device, needs a pump pocket • More challenging implant/explant procedure

HeartWare BTT FDA ‘approval’ ● “Although rates of most key adverse events were comparable, the risk of stroke associated with the HeartWare LVAD necessitates patients and clinicians to discuss all treatment options before deciding to use the device.”

Miniaturization of technology allows for multiple configurations

Fully Implantable HeartMate II

HeartMate III ● Magnetically Levitated VAD ● Pump gaps , textured blood contacting surfaces ● Potential for reduction of adverse events (AI, bleeding, thrombus, stroke) ● Potential to reduce anti-coagulation ● Full support (10L / min) ● Ultra-compact size ● Artificial Pulse ● Improved, modular driveline ● Intrathoracic placement

HeartMate X ● HeartMate II bearing technology ● Miniaturized ● Provides partial and full support ● Highly versatile placement and cannulation ● Scope for less invasive surgery

HeartMate Percutaneous Heart Pump (PHP)

C-Pulse System ● Design:

• • •

Placed extravascular Patient can disconnect May be placed minimally Invasively

● Benefits:

• Increases cardiac output • Increase coronary blood flow • Decreases afterload 62

Summary ● ● ● ●

Heart failure is common and prognosis can be poor VAD therapy has revolutionised treatment Strong supportive evidence Potential Improvements: • Haemodynamic and thrombotic profile • Fully implantable system & transcutaneous charging • Less pump and device infection • better/effective miniaturisation VADs could allow more

•

minimally invasive implants Cost????