FRACP Lectures

Dr Peter Bergin
Advanced Heart Failure Service Alfred Hospital
22nd March 2018
Heart Failure

A Complex
Problem
 Projected HF burden USA

Increases are caused largely by the projected

changes in population demographic

Dunlay, S. M.(2017) Epidemiology of heart failure with preserved ejection fraction Nat. Rev. Cardiol.
Diverse Problems

Mortality

5% Hospital
50% ≤ 5 yrs
1st
•The Problem

2nd
•Diagnosis
 What is Heart Failure?

TypicalSymptoms
± Typical Signs
Structural &/or Functional ↓ CO ±
↑ Filling P
Cardiac Abnormality @ Rest or

Exercise
ESC Guidelines - Acute and Chronic HF 2016
Causes of systolic HF (HFrEF)
 IHD and prior AMI
 >> two-thirds of systolic heart failure.
 IHD present in > 50% of new cases.

 Hypertension
 present in two-thirds of new cases.

 Non-ischaemic idiopathic DCM

 Younger and ≥ 30% familial.
 IDCM in ~ 5–10% of new cases.
 (48,612 pts)

Others 12.7
Diet 5.2 Pneumonia
15.3
WRF 6.8
ACS 14.7

Rx non-
adherence 8.9 Arrhythmia
HT 10.7 13.5

Global Burden of Heart Failure Hospitalization JACC 2014:1123–33

Heart Failure

NYHA I I’m fine 35%

NYHA II I hate stairs 35%

Advanced

NYHA III I love TV 25%

NYHA IV I Can’t Sleep 2-5%

NYHA “V” Alfred – here I come

AHA. Heart and Stroke Statistical Update.

ESC Guidelines - Acute and Chronic HF 2016
ESC Guidelines - Acute and Chronic HF 2016
ESC Guidelines - Acute and Chronic HF 2016
HFrEF LVEF < 40 Sx ± Signs

HFmrEF LVEF 40-49 Sx ± Signs

↑ NP & ≥ 1 of:
• Struct HD ±
HFpEF LVEF ≥ 50 • Diastolic Dysfx
Diverse Physiology
Kidney Liver
Heart

Lungs
Brain
Adrenal

Vessels
Remodelling in Heart failure

o ↑ Size
o ↑ Sphericity
o ↑ MR
Final Common Pathway in HF
Primary goal is discovering
signs and symptoms of high
RA and LA pressures
↑ LA pressure (5-12 to >18-40 mmHg)
→ dyspnoea, pulmonary oedema

↑ RA pressure (2-5 to > 7-20 mmHg)

→ ↑ JVP, liver congestion, SOA
Investigations
Diverse Disease

Systolic Failure Preserved EF Failure

Non LV Failure Non Myocardial Failure

Diverse Phenotype

DCM Sarcoid ARVC

Apical HCM Amyloid Takostubo

 BNP & Diagnosis
1586 ED patients with acute dyspnoea

BNP < 100 pg/ml

=
83.4 % accuracy

A good test to
RULE OUT ADHF 49%
47%

Rapid Measurement of B-Type Natriuretic Peptide in the Emergency Diagnosis of Heart Failure 5%
Alan S. Maisel, NEJM 2002;347:161-167
1st •The Challenge

2nd •Diagnosis

3rd •Treatment
Aims in HF Treatment
 Prevent cardiac dysfunction Heart

 Prevent symptomatic CCF

 Improve quality of life
 Reduce symptoms
 Reverse LV remodelling
Kidney
 Reduce mortality Vascular

It’s not good enough to just reduce symptoms

Eur. Soc. Cardiol. 1997
 ↓ HF
Symptoms

Self Care ↓ LV
Remodelling

HF
AIMS
↑ QOL ↓ HF
Admission
↓ ALL
Mortality
?

ICD

ARNI
The Pharma Evidence in HFREF

Symptomatic HFREF
Pharma for Symptomatic HFREF

ACEi ↓ HF Hospital & Death

βB ↓ HF Hospital & Death
MRA ↓ HF Hospital & Death
ARNI ↓ HF Hospital & Death

2016 ESC Guidelines European Heart Journal (2016) 37, 2129–2200

 Achieve Euvolaemia
Maintain Organ Perfusion
Titrate Slowly
Monitor Kidney & K+
 Euvolaemia
is
EVERYTHING
2L 2 kg 2 gm
 Diuretics – One Job and One Job ONLY
• Symptomatic benefit (other than MRA)
 Oral efficacy reduced with severe HF
 Consider IV and / or combination therapy
Minimise when stable
• Complications - Lots
 ↓ K+ / ↑Arrhythmias / ↓ Na+
 ↑ Diabetes / ↑ cholesterol
 ↑ Renin / Angiotensin
 ↑ Sympathetic drive
• Patient education: Flexible diuretic regimen
 1kg = 1 litre
ESC Guidelines - 2016
McMurray et al. Eur J Heart Fail. 2013;15:1062-73
Device-based treatment
Guidelines for CHF in Australia 2006 / 2011 Grade
Biventricular pacing (CRT) ± AICD:
• NYHA III–IV on OMT A
• Dilated LV > 55mm with LVEF ≤ 35%
• QRS ≥ 120 ms
• Sinus rhythm
Biventricular pacing 2011
• ICD planned, add CRT to reduce the risk of death and HF if A
• NYHA Class II despite OMT
• LVEF ≤ 30%
• QRS ≥ 150 ms (LBBB morphology)

AICD
• Survived cardiac arrest (VF or VT) not due to transient/reversible cause A
• Sustained VT + structural heart disease
• LVEF ≤ 30% ≥ 1 month after AMI or ≥ 3 months after CABG
• LVEF ≤ 35% and Symptomatic CHF (NYHA II–III)
BiVentricular Pacing (CRT)
Electrical Abnormalities → Mechanical Abnormalities
Normal LBBB

Australian Guidelines 2006

 Ischaemic or Dilated CM
 NYHA Class III-IV
 LV EF ≤ 35%
 Dilated LV ≥ 55mm
 QRS ≥ 120 msec
 Sinus Rhythm
MJA 2006; 185: 549–556
AICD in Heart Failure
 2521 pts
SCD-HEFT AICD
 Class II or II
 IHD 52%;
 LVEF ≤ 35%
 23% RRR with AICD

AICD Australian Guidelines 2006

 Survived cardiac arrest (VF or VT) not due to a
transient or reversible cause
 Sustained VT + structural heart disease
 LVEF ≤ 30% ≥ 1 month after AMI or
≥ 3 months after CABG
 LVEF ≤ 35% and Symptomatic CHF (NYHA II–III)

SCD-Heft Bardy, G N Engl J Med 2005; 352:225-237

NICM+Fibrosis = ↓ Prognosis
NICM LGE -
NICM LGE -
n=30

NICM LGE + NICM Mid-wall LGE +

n=31

All events occurring in LGE + (p < 0.01)

103 pts for primary prevention ICD (61 NICM) Iles J Am Coll Cardiol 2011;57:821–8
 Declining Sudden Death
Rates for HF

1% @ 90 days
Shen L et al. N Engl J Med 2017;377:41-51.
Effects of Rx
You Don’t
have to
be Dead
to be Stiff
 HF with Preserved EF- Diastolic HF
 Prevalence 40-50% of HF
Highest > 75 yrs. Women >> Men
 Setting:
Hypertension +++ Diastolic Can’t Fill
Vs Vs
Ischaemia, rarely Infiltration, HCM Systolic Can’t Empty
Comorbidities +++
 Echo
Small cavity, thick walls, big atria
Stiff heart
Increased Natriuretic Peptides

ESC Guidelines 2016

Temporal Trends in HF
Borlaug, B. A. Nat. Rev. Cardiol. 11, 507–515 (2014)
Right Heart Catheter
BP PA PA mean PCW CO

Baseline 156/92 32/14 21 10 4.9

Ex 60W @ 5min 196/93 66/34 47 34 8.8

Diastolic Stress Test

HFpEF: Better Rx Needed
 • Referrals
• Education
Discharge • Flexible Diuretic
• Early Review
• Self Care

Hospital admission risk program (HARP): Chronic heart failure working party report 2003
Rx to Target

Rate of Target Dose

Maggioni EJHF 2013 / IT / 5295

ESC Meeting 2017: 7,117 pts, 547 centres, 36 countries. Sept 2013-Dec 2014.
 • YEP…Pills Work ONLY if You
Prescribe & Up-titrate
• ≥50% of recommended dose =
better long term outcomes

ESC Meeting 2017: 7,117 pts, 547 centres, 36 countries. Sept 2013-Dec 2014.
Heart Foundation 2010
 Patient support by a doctor and a
dedicated multidisciplinary team
involving a comprehensive
predischarge review and
follow-up through a home visit or
specialist CHF clinic is recommended to
prevent clinical deterioration.
Grade A Guideline - CSANZ 2006
Heart Foundation 2010
 Survival estimates for 115,803 DM adults age ≥65 years

DM. No HF
Mortality
3.7 /100 Pat-Y

DM + HF
Mortality
32.7 /100 Pat-Y

Alain G. Bertoni et al. Dia Care 2004;27:699-703

 Sodium–GLucose co‐Transporter 2 inhibitors

SGLT2 inhibitor
empagliflozin

European Journal of Heart Failure 24 AUG 2017

 CV death, nonfatal MI, nonfatal CVA

Empagliflozin (SGLT2i)
NEJM 2015;373:2117-2128
• Lower rate of CV death but not CVA or MI
• Safe & beneficial for prevention of HF
hospitalizations in type 2 diabetes mellitus

Zinman B NEJM 2015;373:2117-2128

Sodium-Hydrogen Exchanger (NHE) -dependent pathways

MRA

SGLT2i

Milton Packer Circulation. 2017;136:1548-1559

EMPEROR HF clinical trial programme will
evaluate the efficacy and safety of
empagliflozin in HF ± type 2 diabetes

Est Study Completion: June, 2020

 Confirm – HF
304 ambulatory HF patients with LVEF ≤45%
2016 ESC HF Guidelines
1o EP: 6MWT improved at Wk 24
FCM v placebo: 33 ± 11m, P=0.002
NB: Patients with iron deficiency need to be
screened for any potentially treatable/reversible
causes (e.g. GI sources of bleeding).
Ferritin <100 ng/mL or 100–300 ng/mL if transferrin saturation <20%
FCM: ferric carboxymaltose

Eur Heart J. 2015 Mar 14; 36(11): 657–668

ESC Guidelines: Acute and chronic HF 2012. European Heart Journal (2012) 33, 1787–1847
Outpatient HF – Not Always Stable

Annualized rate 9.2%

964 outpatients with Stage C HFREF. JACC HF 2017;5:528–37

 Red Flags for Advanced HF Therapy
CLINICAL FEATURES
• Hypotension: Persistent SBP<90mmHg
• Persistent NYHA 3+ symptoms, oedema
• Hospitalizations 2+ inMEDICATION
12 months
• Down-titration of ACE/ARB, Beta blocker
• Recurrent 2+ ICD shocks
• Increasing diuretic need
INVESTIGATIONS
• Prior or ongoing inotrope requirement
• End organ dysfn (renal, hepatic)
• LVEF<20%
• High/rising BNP/NT-proBNP
• Low Serum Na+
Think VADs
A VAD Evolution
Past Current Future

HeartWare Heartmate III

PVAD
Novacor
Heartmate
XVE Rematch

Heartmate X
Heartmate II
Cardiomyopathy: Morphology

Dilated

LV RV
Hypertrophic

Restrictive
CARDIAC MRI: LGE IN CARDIOMYOPATHY
Ischaemic IDCM
cardiomyopathy

Sarcoid Amyloid
cardiomyopathy cardiomyopathy
HCM - Pathophysiology
 Abnormal Hypertrophy
 Preserved LV EF ± LV obstruction
 Fibrosis & Diastolic Dysfunction
 Microcirculatory dysfunction

Myocyte Disarray Hypertrophy Fibrosis

 Cardiac arrest (VF)
AICD Sustained VT

2011 FH of SD
Unexplained syncope
LVH ≥ 30 mm

NSVT (Holter)
Abn exercise BP

ACCF/AHA HCM Guideline 2011 ICD not recommended

AICD 2014
Case 1
 26 yo female previously fit
 2 weeks “vaguely unwell”
 2 days later PND
 APO
 BP 85/50, HR 120/m
 Anuric
 TnI 26
 Lymphocytic Myocarditis
Beware ADHF in Young
Myocarditis– Cardiac MRI
Oedema T2 Hyperaemia T1

Irreversible Injury
Late Enhancement Gd
Christiaan Barnard
Groote-Schuur Hospital
December 3rd 1967
 Basic Indications / CI

 Outcomes

 Major Short / Long Term Problems

 Basic Types of ImmunoRx

 Complications of ImmunoRx

 The Immunocomproised Pt
 Tx Surgery
Orthotopic Heart Tx

88
Number of adult and pediatric heart transplants by year
(transplants: 1982–2015) and geographic region.

The Journal of Heart and Lung Transplantation 2017 36, 1037-1046DOI: (10.1016/j.healun.2017.07.019)
Copyright © 2017 Terms and Conditions
Indications for Cardiac Tx
 Severe symptomatic heart failure
 Despite maximally tolerated evidence-based medical Rx
 Mechanical cardiac support
 Cardiogenic shock
 Frequent repeated discharges from an AICD
 Intractable angina
 Despite optimal medical, interventional and surgical
treatment
 Low EF alone is NOT an Indication
National Protocol for Organ Transplantation TSANZ 2010
Contraindications
 Age is not by itself a contraindication
 Comorbidities that result in high mortality/morbidity risk
 Active malignancy
 Uncontrolled Infection
 HIV, Hep B, Hep C may not be absolute C/I
 Complicated diabetes
 Morbid obesity (BMI>30)
 Lifestyle factors that result in poorer outcomes
 Substance abuse (alcohol, smoking, illicit drugs)
 6 months abstinence recommended before consider listing
 Irreversible damage of other organ systems that preclude
rehabilitation
 Rejection

 Leading early mortality - 30%

 Early diagnosis essential
 Biopsy current "gold standard"
 90% within 6 months.
 / young at high risk
 Early Rx essential
 Three Signal Model of T cell Activation

Antigen Presenting Cell

Steroids

Signal 1 Signal 2 Signal 3

ATG Anti-IL-2R
OKT3
MHC II B7 Interleukin-2

Antigen
Interleukin-2 receptor
Sirolimus
TCR
CD45 CD4 CD3 CD28 Everolimus
Calcineurin Cyclosporine TOR
Pathway & Tacrolimus Pathway MMF
Steroids Cytokine gene Purine
nucleus Cell Cycle Synthesis
 Late Mortality

Figure 17 Cumulative incidence of the leading causes of death for adult heart
transplants performed between January 1992 and June 2008. ISHLTx Registry 2010
 Transplant Coronary Disease

Non - Transplant Transplant Disease

 Proximal  Distal
 Localised  Diffuse
 Eccentric  Concentric
 Calcified  Non-calcified

TCD = intimal hyperplasia & interstitial fibrosis

Adult heart transplants: Kaplan-Meier survival by era
(transplants: January 1982–June 2015. n = 113,758)

The Journal of Heart and Lung Transplantation 2017 36, 1037-1046DOI: (10.1016/j.healun.2017.07.019)
 Overview
Benefit of Heart Transplantation
 Transplantation is highly effective treatment
 Average survival in eligible patients who are unable
to have transplant is < 2 years
 ANZ median survival is 14 years
 >1/3 survive more than 20 years
 About 80 heart transplants are performed each year
in Australia
IF YOU WISH TO BECOME A DONOR
SIGN UP BEFORE IT’S TOO LATE