Post on 12-Jun-2022
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