Device Therapy and Heart

Failure

Dr Kiran Patel

Consultant Cardiologist & Hon Reader, Heart of England NHS Trust & Univ of Warwick

Medical Director, NHS England (West Midlands)

Summary

• Epidemiology

• Menu of therapy and its evolution

• Dysynchrony and Devices

Projected Heart Failure Admissions

0

20,000

40,000

60,000

80,000

100,000

120,000

2001

/02

2006

/07

2011

/12

2016

/17

2021

/22

2026

/27

Nu

mb

er

of

ad

mis

sio

ns

Men over 45

Women over 45

Total

Annual absolute mortality in the E.U. for

different pathologies

0 100000 200000 300000 400000 500000 600000 700000 800000

heart failure

sudden cardiac death

All cancers combined

lung cancer

colon/rectum cancer

breast cancer

prostate cancer

bowel cancer

ovary cancer

myocardial infarction

Mortality statistics for HF

• 40% die within 1 year of diagnosis

• 10% pa mortality thereafter

• 5% of all deaths

NYHA II NYHA III NYHA IV

CHF 12 26 56

Other 24 15 11

SCD 64 59 33

1 yr mortality 3-25% 10-45% 50-80%

MERIT Ix 1999

HF Therapy: Aetiology

• Cardiac – Ischaemic (65%)

– HT

– Valvular

– Arrhythmic

– Pericardial

• HOCF – Pregnancy

– Pagets etc.

• Systemic – Vasculitis

– Infection • Chagas, viral

– Genetic • HCM, DCM, DMD

– Metabolic • DM, amyloid, sarcoid,

storage disorders

– Toxic • EtOH, drugs, Fe

overload

Exclude a Differential diagnosis

• Lung disease

• Obesity

• Mechanical • chest wall or diaphragm

abnormalities

• Fluid retention • Drug induced

• Venous insufficiency

• Renal failure

• Liver failure

• Hypoalbuminaemia

• PE

• Anaemia

• Thyroid disease

• Deconditioning

• Depression/anxiety

Decompensated HF: Seek Precipitant

• ACS: Angina/MI

• Arrhythmia

• Valvopathy deterioration

• Myocarditis

• Tamponade

• Dissection

• Shunts

• HT crisis

• Anaemia

• Alcohol

• Infection

• Iatrogenic – XS fluids, drugs

• Pregnancy

• PE

• Thyroid disease

• Brain injury

• Renal failure

• Asthma

• Drug abuse

Dining on HF therapies in 2000

• Starters • Diuretics

• Rehabilitation

• Advice

• Main course • ACEI

• blockers

• Spironolactone

• Digoxin

• Dessert • Transplantation

• Coffee • High risk surgery

Cumulative percent reduction in odds of death at 24 months associated with sequential

treatments compared with no treatment.

Fonarow G C et al. J Am Heart Assoc 2012;1:16-26

Incremental benefit of heart failure therapies

COMPANION: CRT-D mortality reduction

Compared to ACE-Inhibitor and ß-blocker studies

no ß-blockers

or ACE-Inh ACE-Inh

ß-blockers

and ACE-Inh ß-blockers

and ACE-Inh

and CRT-D

COMPANION

- 36%

SOLVD

CONCENSUS

-16 to -31% CIBIS II

COPERNICUS

- 35%

NYHA class

I II III IV

Loop diuretic if oedema (Furosemide or bumetanide)

ACEI (Ramipril)

BB (Bisoprolol, Carvedilol)

ARNI (Sacubitril / Valsartan)

Sinus node inhibitor (Ivabradine)

MRA (Eplerenone)

MRA (Spironolactone)

CRT and ICD (once on maximum tolerated medical therapy)

Therapy for HF in 2017

60%

70%

80%

90%

100%

0 60 120 180 240 300 360

Days in Trial

Cu

mu

lati

ve

Su

rviv

al

QRS Duration (msec)

<90

90-120

120-170

170-220

>220

Wide QRS – Proportional Mortality Increase

• NYHA Class II-IV patients

• 3,654 ECGs digitally scanned

• Age, creatinine, LVEF, heart rate, and QRS duration found to be independent predictors of mortality

• Relative risk of widest QRS group 5x greater than narrowest

1 Gottipaty V, Krelis S, Lu F, et al. JACC 1999;33(2) :145 [Abstr847-4].

Vesnarinone Study1 (VEST study analysis)

Sinus

node

AV

node

Bundle

branch block

Delayed conduction

• Delayed AV sequence

• Mitral regurgitation

• Decreased filling time

Ventricular Activation Is Delayed

Sinus

node

AV

node

Bundle

branch or

diffuse block

Delayed conduction

• Abnormal RV-LV sequence

• Abnormal left intraventricular

activation sequence

• Non-uniform wall strain

Ventricular Contraction Is Uncoordinated

Dysynchrony

• Reduced efficiency • Contracting segments deform relaxed segments – wastes

energy

• Paradoxical septal motion wastes energy

• 27% with normal QRS<120 have mechanical

dysyncrony

• 60% with normal QRS 120-150 have mechanical

dysyncrony

• 70% with normal QRS >150 have mechanical

dysyncrony

Preventing SCD in HF

• ACEI/ARB • No consistent effect on arrhythmias

• Aldosterone antagonism • Eplerenone reduces SCD by 33% if LVEF<30%

• blockers • 40-55% SCD reduction in CAPRICORN

• Antiarrhythmic drugs • GESICA: 28% mortality reduction with amiodarone in NYHA

III and IV but NS SCD reduction

• CHF-STAT: negative trial in patients with LVEF<40% and >10 VE’s per hour

• SCD-HeFT: No benefit of amiodarone

• Devices

Cardiac Resynchronisation Therapy

(CRT)

Atrial synchronous biventricular pacing

•Right Atrium

•Right Ventricle

•Left ventricular lead via coronary sinus

Shown to reduce morbidity and mortality.

Why CRT?

• Addresses pump failure by improving

• symptoms and hence QoL

• NYHA functional class

• exercise capacity

• Reduces mortality (CARE-HF and non-significant trend in COMPANION study)

• Multiple studies confirming morbidity reduction: PATH-CHF, MUSTIC, MIRACLE,MIRACLE-ICD,CONTAK-CD, COMPANION

CRT trials

TRIAL NO OF PATIENTS INCLUSION

PATH-CHF 42 NYHA III/IV

QRS>120, PR>150

InSync 103 NYHA III/IV

QRS>150, LVEDD>60

LVEF<35

MUSTIC-SR 131 NYHA III/IV

QRS<150, LVEDD>60

LVEF<35

MIRACLE 452 NYHA III/IV

QRS>130, LVEDD>55

LVEF<35

CRT Trials

• Most trials excluded patients in AF

• 30% of patients in Class III/IV have or will

develop AF

• RBBB patients may also benefit (though

not seen in CONTAK-CD)

• Is mechanical dysynchrony more reliable

as a selection tool?

Why AICD?

Addresses arrhythmic death and hence mortality:

• MADIT II: 31% mortality reduction in patients with low LVEF

• SCD-HeFT: 23% mortality reduction in patients with symptomatic HF and low LVEF

• BUT NOTE: ICD therapy alone increases hospitalisation – reinforces need for CRT combination in HF

Antiarhythmic drugs post MI

Trial Drug Higher

mortality

Neutral

mortality

Lower

mortality

IMPACT Mexilitine vs P Y

CAST 1 Flecainide Y

Encainide vs P Y

CAST II Moricizine vs P Y

BLOCKERS Propranolol Y

Timolol Y

Metoprolol Y

Acebutolol Y

Julian D,L Sotalol Y

SWORD D sotalol Y

EMIAT Amiodarone vs P Y

CAMIAT Amiodarone vs P Y

Diamond MI Dofetilide vs P Y

Alive Azimilide vs P Y

Risk stratification for ICD in HF

• Aetiology

• NYHA Class

• Syncope

• LVSD

• QRS

• QT dispersion

• Holter monitoring

• SAECG

• HRV and BRS

• TWA

• EPS

• BNP

• Innervation-perfusion mismatch

Increase in the Use of Implantable Cardioverter-Defibrillators (ICDs) in the United States

Jauhar, S. et al. N Engl J Med 2004;351:2542-2544

ICD therapy options

Sensing

FVT detection

VT detection

Brady detection

Defibrillation

Burst

Ramp

Ramp +

Cardioversion

Stimulation

VF detection

DiMarco, J. P. N Engl J Med 2003;349:1836-1847

Normal Function of an Implantable Cardioverter-Defibrillator

ICD complications

• Acute mechanical

• Infection 0.5-1.6%

• Inappropriate shock 6% at 1yr, 16% at

5yrs

• Anxiety, depression etc 14-50% - reduced

by 25% with cardiac rehab

Single or dual chamber ICD?

• VR • No pacing required

» SAN + AV function intact

» Permanent AF

» Primary prevention ICD

• DR • Those requiring brady pacing for SND

• Atrial arrhythmias requiring discrimination e.g. AF

in HF??

SCD incidence and total events

INCIDENCE TOTAL EVENTS

General population

Previous CV event

EF<35% or HF

High risk Post MI

Cardiac arrest, VT/VF survivors

NICE Guidance 2006

• Secondary prevention • VT/VF survivors with no reversible/treatable cause

• Symptomatic VT

• Sustained VT with LVEF<35% and <NYHA 3

• Primary prevention • Familial high risk of SCD

• >4/52 post MI and either – LVEF<35% (<NYHA 3) AND NSVT AND inducible VT on

EPS

OR

– LVEF<30% (<NYHA 3) AND QRS >120ms

CABG Patch trial

Bigger, J. T. et al. N Engl J Med 1997;337:1569-1575

CABG Patch trial

• Revascularisation is highly effective at

reducing M&M risk

• SAECG poor at risk stratification

MADIT II

• CHD >1/12 post MI

• LVEF <30%

• Randomised to optimal therapy (n=490) vs

optimal therapy + ICD (n=742)

• 18 month follow up

MADIT II

Moss, A. J. et al. N Engl J Med 2002;346:877-883

Problems in the real world

• There is a limit to ICD efficacy: halving SCD only

reduces overall mortality by 20%

Cause of death Without ICD (%) With ICD (%)

SCD 40 20

Pump failure 40 40

AMI 10 10

Other deaths 10 10

Total deaths 100 80

Enrollment and Randomization of Patients.

Køber L, et al. N Engl J Med 2016

DANISH

Rate of Death from Any Cause (Primary Outcome) in Prespecified Subgroups.

50% reduction

Enrollment and Randomization of Patients. DANISH

Køber L, et al. N Engl J Med 2016

2005

19 year old girl

NYHA class I

6 months: Palpitations, abrupt onset, lasting 5 s, ~200 bpm

+ flushing, no syncope or pre-syncope

3 months: Vision went “hazy” and she felt as if she was going

to faint (pre-syncope)

DH: Ramipril 2.5mg od; Bisoprolol 2.5mg od

Intolerant to high dose BB, refused increase in

ramipril

FH: Mother had MVR at 55 yrs

History

ECG

2005: 24-hr tape: NSVT

FBC, U&E’s, LFTs TFTs, iron studies, CRP, autoimmune screen, serum

protein electrophoresis: normal

Echo: LVEF 28%

Progress

2007: NYHA class I

LVEF 20-25%

Holter: NSVT

2009: NYHA class I

Some palpitations; no associated symptoms

Question

Should we offer ICD therapy ?

1. Yes

2. No

CMR

2014

EDV: 199 ml, ESV: 130 ml, EF: 35 %

Question

Should we offer ICD therapy ?

1. Yes

2. No

May 2014: Change in NICE guidance: offered ICD, but declined

Progress

May 2014: Change in NICE guidance: offered ICD, but declined

May 2015: Found lifeless at home

Certified dead in A&E

Age 29

Progress

NICM: a very general term

Death, heart failure hospitalization or appropriate ICD shocks

LGE on CMR, irrespective of extent or segmental pattern

HR: 8.2 (95% CI 2.2 to 30.9), p = 0.002

SCD in NICM: role of CMR

Wu KC, et al. JACC 2009;51:2414-51

SCD OR ABORTED SCD

Shaded areas represent 95% CIs.

472 patients with DCM (Royal Brompton)

SCD in DCM: role of CMR

Gulati et al. JAMA. 2013;309(9):896-908

Fibrosis: 29.6%

No fibrosis: 7.0%

HR: 5.24 [95% CI, 3.15-8.72]

Absolute risk difference: 22.6%

(P < 0.001)

MDT discussions

Previous MI *

DCM with presumed

arrhythmic syncope

NYHA CLASS I-III, LVEF < 35%, QRS < 120 ms

HIGH RISK FEATURES LOW RISK FEATURES

DCM with no scar

- PVC’s, - NSVT

DCM

+scar *

or: >10PVC’s/hr

and/or NSVT

INTERMEDIATE

RISK FEATURES

RISKS OF ICD GREATER THAN BENEFIT

HAEMODIALYSIS FRAILTY Recurrent

pump failure

PATIENT

PREFERENCE

MULTIPLE COMORBIDITIES

SURVIVAL <1 YR

New technology

• Remote monitoring

• Contractility sensing

• Minimal RV pacing

• Rate response

• Leadless ICD

• Bridge to ICD

Implant

Follow-up

Clinic

Home

• Only truly wireless follow-up with Leadless ECG

• Monitor in patient’s home will capture the device-triggered alerts

Telemetry and Remote

Monitoring Benefits

• Removes programming head from sterile field and maintains telemetry throughout procedure for better implant management

REM-HF: device remote monitoring in HF

RCT: Remote monitoring vs usual care

Primary endpoint: Death from any cause or unplanned HF hospitalisation

Secondary endpoint: Cardiovascular death, cardiovascular death / cardiovascular hospitalisations

No difference in secondary endpoints

The Concept: Fluid <->

Impedance

Heart Failure Worsening

Fluid Retention

Decrease in Impedance (W)

No reduction in all-cause death or CV

hospitalization compared with standard

clinical management

OptiLink HF study: intrathoracic impedance in HF

Prospective, multi-centre, randomized, and unblinded study

N=1002 randomised to alert transmission or no transmission.

Follow-up: 23 months

Böhm M, et al. Eur Heart J 2016;37:3154-3163

TOTAL MORTALITY

van Everdingen WM, et al. JACCEP 2015;1:225–37

LV LEAD DEACTIVATION

LV LEAD REPLACEMENT

Quadripolar LV leads in CRT: outcomes

St Jude systems

N=18,406 quadripolar

N=5,164 bipolar

Subcutaneous ICD

• Low DFT

• Doesn't have pacing capability,

• Uses • nonobstructive hypertrophic cardiomyopathy

• Brugada syndrome

• Idiopathic HF

• HF without an indication for CRT

Bridge to ICD: Wearable

defibrillator • Vest of electrodes and battery

• Patient can go home

• Can be rented

• Remote monitoring possible

• Patient can withold shock so delivery only occurs after LOC

• Bridges period of uncertain risk and decision making on ICD Rx

• When should ICD be implanted post-MI? Not early (DINAMIT). LVSD may recover post MI

• LVSD may recover with surgery e.g.CABG

• Bridge during transplant assessment

• Myocarditis – short term high risk of VF

End of Life

• Does switching off a device constitute

physician assisted suicide? • Decision to switch off with 2 clinicians

• Discuss at implant for EoL wishes

• State programming can change with time/illness

• Re-discuss and document at EoL

When to discuss deactivation?

• When debating/discussing DNR

appropriateness

• When death likely

• When SCD would be a relief

• At consent and annual reinforcement

Conclusions

ICD in NICM: DANISH adds to evidence, but no definite guidance for

now – helps justify decisions at MDT however

Contractility sensor in CRT:Now the gold-standard for AV/VV optimisation in CRT

VNS in HF: No benefit from VNS

Impedance monitoring: No benefit ?

Quadripolar leads in CRT: Should be standard of care

Device RTM in HF: No benefit in survival / HF hospitalisations

Wrong study endpoints ?

HF therapy for dinner

• Starters • Diuretics

• Rehabilitation

• Main course • ACEI

• blockers

• Spironolactone

• Eplerenone

• ARB

• ARNI

• Digoxin

• Levosimendan

• Dessert • CRT (D)

• ICD

• Coffee (not hungry) • High risk surgery

• After dinner mints (still hungry?)

• Transplantation

• VAD – bridge or destination

• Carriages • Palliative care

• EECP

• Sleep disordered breathing

• Plasmapheresis

• Reincarnation/after-life • Gene therapy

• Stem cells

• rEPO or iv Fe