Contemporary heart failure management

Dr Joris Mekel

GP meeting

26 March 2015

Case 1

• Mr T. McI. – 49 years

• Viral illness June 2014

• Progressive dyspnoea to NYHA FC III

• 6-8 mid-strength beers/day

• Unremarkable blood tests

Case 1

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

II

PID: 45948 08/22/2014 08:25:00 MCINNERNEY, TROY05/20/1965 DOB 49 years Male Dept

RoomTech NIK

Rx:Dx:

Req MD:Ref MD: DR CHEEMA

Rate 104PR 182QRSD 108QT 342QTc 449

--AXIS--P 77QRS -4T 79

Sinus tachycardia, rate 104 bpm.Normal PR intervalPossible Left atrial enlargementSeptal infarct , age undetermined

tj

CC: Dr. A. Cheema

- ABNORMAL ECG - Confirmed By: Tony Jackson 08/26/2014 15:58:44

GE MAC35 25 mm/sec 10 mm/mV F 60~ 0.5 - 150 Hz

Case 1

Case 1

• Angiogram normal

• Management:

– Admitted to hospital

– Diuretics, ACE inhibitor, β-blocker, Spironolactone, thiamine

Definition

• An inability for the heart to maintain sufficient blood flow to meet the metabolic requirements of the body, or to do so only at a raised filling pressure.

An inability for the heart to maintain sufficient blood flow to meet the metabolic requirements of the body

…or to do so only at a raised filling pressure.

Definition

• Clinical syndrome characterised by diminished effort capacity and dyspnoea due to cardiac dysfunction.

Compensatory Mechanisms

Frank-Starling Mechanism

a. At rest, no HF

b. HF due to LV systolic dysfunction

c. Advanced HF

Compensatory Neurohormonal Stimulation

Decreased Cardiac Output

Sympathetic nervous system

Renin-angiotensin system

Antidiuretic hormone (vasopressin)

Heart rate

Contractility Vasoconstriction Circulating volume

Anteriolar

Maintain blood

pressure

Cardiac output

Stroke volume

+

- +

Venous

Venous return to heart

( preload)

Peripheral edema and pulmonary

congestion

Compensatory Mechanisms

Frank-Starling Mechanism

a. At rest, no HF

b. HF due to LV systolic dysfunction

c. Advanced HF

Diagnosis

• History & clinical examination

• Blood tests (esp TFT, ferritin)

• ECG

• CXR

• Echocardiogram

• Angiography, cardiac catheterisation

• MRI

Diagnosis

• History & clinical examination

• Blood tests (esp TFT, ferritin)

• ECG

• CXR

• Echocardiogram

• Angiography, cardiac catheterisation

• MRI

Management

• Address underlying cause

– Correct ischaemia, repair/replace valves etc

• Non-pharmacological

– Avoid toxins

– Sodium & fluid restrict

– Exercise

Aetiology

• Ischaemia • Post-viral myocarditis • Hypertension • Valvular • Idiopathic - incl genetic • Nutritional eg Beri-beri • Toxins esp alcohol • Metabolic – haemochromatosis, Gaucher’s • Peripartum • Tachycardiomyopathy • Thyrotoxicosis • HOCM • Restrictive • Constrictive pericarditis • Rare eg non-compaction

Management

Lifestyle Modifications:

• Weight reduction

• Discontinue smoking

• Avoid alcohol and other cardiotoxic substances

• Exercise

Medical Considerations:

• Treat HTN, hyperlipidemia, diabetes, arrhythmias

• Coronary revascularization

• Anticoagulation

• Immunization

• Sodium restriction

• Daily weights

• Close outpatient monitoring

Management

• Pharmacological

– Diuretics

– ACE inhibitors

• ARB’s

– β-blockers

– Spironolactone

– Digoxin

– Ivabradine

Preload reduction

• Diuretics

• Nitrates

Compensatory Mechanisms

Frank-Starling Mechanism

a. At rest, no HF

b. HF due to LV systolic dysfunction

c. Advanced HF

Case 1

– β-blocker uptitration limited by hypotension

– Ivabradine started

Case 2

• Mr B.J. – 76 years

• Presents with progressive dyspnoea for a few months

• No angina, no history of hypertension, no recent infective illness, little alcohol

• Admitted to hospital with heart failure.

• Oedema, JVP elevated, heart rate 100 bpm, regular, BP normal.

• No murmurs

Case 2 - investigations

• Blood tests unremarkable

• TSH, ferritin

Case 2 - investigations

Case 2 - investigations

• ECG

Case 3 - investigations

Case 4 - investigations

Case 2 - management

• Diuretics

• ACE inhibitor

• Spironolactone

• β - blocker

• Aspirin

• Statin

• ACE-I & β – blocker uptitration limited by hypotension

• Symptomatic improvement but LVEF remained at 24%, NYHA FC II

Afterload reduction

• Concept evolved in 1970’s

• Sodium nitroprusside

• Phentolamine

• Nitrates

• Hydralazine

642 men with heart failure Randomised to Isosorbide mononitrate & Hydralazine vs Prazosin vs placebo 36% relative mortality risk reduction at 3 years (36% vs 47%)

• 253 patients, NYHA FC IV • Placebo vs Enalapril • Mortality risk reduction at 6 months showed a

40% relative risk reduction (26% vs 44%)

• 7601 patients with heart failure • Candesartan vs placebo (patients who tolerated ACE-I

were taking them • 10% relative risk reduction at 38 months

3023 patients, NYHA II – IV, EF >40% No effect on mortality, reduced hospital admissions

• 2548 patients, NYHA II – IV, EF <40% • 15% relative risk reduction in composite outcome of death or

hospital admission for heart failure.

• 2028 patients, ACE intolerant

• 23% relative risk reduction in death/hospital admission for heart failure

β-blockers

• MERIT-HF

• CIBIS

• Carvedilol

• SENIORS

Carvedilol

1094 patients, LVEF <35% Assigned 2:1 to Carvedilol or placebo 65% relative risk reduction (3.2% vs 7.8%) in death at 6 to 12 months

Bisoprolol

2647 patients, LVEF <35%, NYHA III or IV Bisoprolol or placebo 34% relative risk reduction (11.8% vs 17.3%) in mortality at 1.3 years

Metoprolol

3991 patients, LVEF <40%, NYHA II to IV 34% relative risk reduction (7.2 vs 11%) in mortality at 1 year

Nebivolol

2128 patients, >70 years, admission in 12 months prior or LVEF<35% Nebivolol vs placebo 14% relative risk reduction (31.1 vs 35.3%) in death/HF hospitalisation at 21 months

Aldosterone antagonists

• Spironolactone

• Eplerenone

Spironolactone

1663 patients, severe heart failure, LVEF <35% Spironolactone 25 mg vs placebo 30% relative risk reduction (35 vs 46%) in death at 24 months

Eplerenone

2737 patients, NYHA II, LVEF <35% Eplerenone (up to 50 mg) vs placebo 37% RR reduction (18 vs 26%) in death/HF hosp at 21 months

Digoxin

6800 patients, LVEF < 45% Digoxin 250 μg daily vs placebo No effect on mortailty (OR 0.99), 6% fewer hospitalisations at 37 months

Inotropes

• Increase mortality but sometimes needed for decongestion and symptom relief.

Case 2 - management

• CRT

Cardiac resynchronisation therapy

Cardiac resynchronisation therapy

Case 2 - management

ECG’s pre & post

Case 2 - management

Case 2 - management

BP improved

Beta-blocker uptitrated to target

ACE-I increased to ½ target

Asymptomatic

Case 3

• Mrs J.H. – 86 years

• IHD – PCI’s to RCA & left main

• Develops heart failure with persistent atrial fibrillation

• Cardioversion & Sotalol, later Amiodarone

Case 3

• Syncope with pauses

• Pacemaker

Case 3

Case 4

• Mrs M.J. – 85 years

• Admitted with heart failure – NYHA FC III

• No angina

• Hypertension, hyperlipidaemia

• Long-term steroid therapy for PMR

Case 4

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

II

PID: 38311 06/14/2013 08:14:10 JONES, MIRIAM08/15/1927 DOB 85 years Female Dept

RoomTech SE

Rx:Dx:

Req MD:Ref MD: MEKEL, HARRIS

Rate 70PR 152QRSD 130QT 432QTc 466

--AXIS--P 62QRS -28T 93

Normal sinus rhythm with sinus arrhythmia, rate 70 bpmRight bundle branch blockMinimal voltage criteria for LVH, may be normal variantSeptal infarct , age undetermined

TJ

- ABNORMAL ECG - Unconfirmed Study 00// 00:0:

GE MAC35 25 mm/sec 10 mm/mV F 60~ 0.5 - 150 Hz

Case 4

• Medications:

– Candesartan, Rosuvastatin, Aspirin, Frusemide, ISMN, Carvedilol.

Coronary angiogram

Coronary angiogram

Case 4

• PCI to LAD, complicated by VF arrest, successfully resuscitated.

1 World Health Statistics, World Health Organization, 1995.

2 American Heart Association, 2002 Heart and Stroke Statistical Update.

HF Incidence and Prevalence

• Prevalence

– Worldwide, 22 million1

– United States, 5 million2

• Incidence

– Worldwide, 2 million new cases annually1

– United States, 500,000 new cases annually2

• HF afflicts 10 out of every 1,000 over age 65 in the U.S.2

• Extrapolating to regional Victoria

– 22,000

Prevalence of HF by Age and Gender

United States: 1988-94

0

2

4

6

8

10

Percent of

Population

20-24 25-34 35-44 45-54 55-64 65-74 75+

Males

Females

Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association

Projections of prevalence of cardiovascular disease in 2010-2030 (USA)

Year

CAD

crude prevalence, %

HF crude prevalence, %

All CVD* crude prevalence, %

2010 8.0 2.8 36.9

2015 8.3 3.0 37.8

2020 8.6 3.1 38.7

2025 8.9 3.3 39.7

2030 9.3 3.5 40.5

% Change 16.6 25.0 9.9

*Includes hypertension, CAD, HF, stroke Heidenreich PA. Circulation 2011;123:933-944

30%

70%

Diastolic Dysfunction

Systolic Dysfunction

(EF < 40%) (EF > 40 %)

Left Ventricular Dysfunction • Systolic: Impaired contractility/ejection

– Approximately two-thirds of heart failure patients have systolic dysfunction1

• Diastolic: Impaired filling/relaxation

1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200

Economic burden of

Chronic Heart Failure

Hospitalisation accounts for most CHF-associated costs

Stewart S, et al. Eur J Heart Fail 2002;4:361–71.

Primary Care

Outpatient referral

Drug treatment

Post-discharge outpatient visits

Hospital admissions

NHS data, United Kingdom

5% 6% 2%

Ivabradine

Logeart D, et al. Eur Heart J 2012;33 - Abstract Supplement 485

Elevated HR at discharge is a predictor of one-year mortality in HF patients (OFICA)

N=1658 (170 hospitals); median HR at discharge 71 bpm; 1 year mortality: 33%

41%

Audit of 100 CHF consecutive patients*, >50% had heart rate >70bpm

53.4% HR > 70 bpm 20.3% HR > 80 bpm

(N=20)

(N=54)

Cowie MR and Davidson L. Int J Clin Pract 2012; 66: 728 – 730

Pati

ents

Heart rate Reproduced with permission from M. Cowie,

Royal Brompton Hospital, UK

*sinus rhythm, EF < 40%, completed β-blocker uptitration [n=54] or intolerant of a β-blocker [n=20]

Analysis restricted to patients for whom the specialty of the first BB supply was known Source: Data from PBS 10% sample, Department of Human Services (CO8526)

Systolic Heart Failure treatment with

the If Inhibitor Ivabradine Trial

Swedberg K, et al. Lancet. 2010;376:875-85

Background

Elevated heart rate is associated with poor outcome in a number of

cardiovascular conditions including heart failure

Heart rate remains elevated in many heart failure patients despite

treatment by beta-blockers

Ivabradine is a novel heart rate-lowering agent acting by inhibiting the

If current in the sino-atrial node

Primary objective

To evaluate whether the If inhibitor ivabradine improves

cardiovascular outcomes in patients with

1.Moderate to severe chronic heart failure

2.Left ventricular ejection fraction ≤35%

3.Heart rate ≥70 bpm and

4.Optimised background therapy

Swedberg K, et al. Lancet. 2010;376:875-85

Patients and follow-up

Median study duration: 22.9 months; maximum: 41.7 months

6558 randomized

3268 to ivabradine 3290 to placebo

3264 analysed

1 lost to follow-up

3241 analysed

2 lost to follow-up

7411 screened

Excluded: 27 Excluded: 26

Swedberg K, et al. Lancet. 2010;376:875-85

Study endpoints

Primary composite endpoint

Cardiovascular death

Hospitalisation for worsening heart failure

Other endpoints

All-cause, CV and HF death

All-cause, CV and HF hospitalisation

Composite of CV death, hospitalisation for HF or non fatal MI

NYHA class / Patient & Physician Global Assessment

Swedberg K, et al. Lancet. 2010;376:875-85

Chronic HF background treatment

89 91

84

61

22

3

90 91

83

59

22

4

0

10

20

30

40

50

60

70

80

90

100

Beta-blockers ACEIs and/or ARBs

Diuretics Aldosterone antagonists

Digitalis ICD/CRT

Patients

(%)

Swedberg K, et al. Lancet. 2010;376:875-85

Ivabradine

Placebo

n= 3241

n=3264

Antialdost

antag, %

Diuretics,

%

BB,

%

ACEI/ARB, or

total, %

Baseline HR,

bpm

Study

61 84 89 91 80 SHIFT, 2010 (n=6505)

29 86 ST 82 79 SENIORS, 2005 (n=2128)

17 90 55 ACE+ ST 73 CHARM Added, 2003 (n=2548)

38 77 72 ST 71 HEAAL, 2009 (n=3846)

NA 85 7 ST 80 SOLVD 1991 (n=2569)

55 98 2 ST 80 CONSENSUS 1987 (n=253)

20 99 ST 96 83 COPERNICUS, 2001 (n=2289)

NA 99 ST 96 80 CIBIS II, 1999 (n=2647)

NA 91 ST 95 83 MERIT HF, 1999 (n=3991)

ST 100 10 94 81 RALES 1987 (n=253)

References supplied upon request.

Swedberg K, et al. Lancet. 2010;376:875-85

Mean heart rate reduction of 8 bpm

with ivabradine

0 2 weeks 1 4 8 12 16 20 24 28 32

90

80

70

60

50

67

75 75

80

64

Heart rate (bpm)

Ivabradine

Placebo

Months

Ivabradine reduced composite of CV death

and hospitalisation for worsening HF

Swedberg K, et al. Lancet. 2010;376:875-85

0 6 12 18 24 30

40

30

20

10

0

18% RRR

p<0.0001

Event Rate (%)

Lines

separate by 3

months

Ivabradine

Placebo

NNT = 26

Months

n=6505

Effect of ivabradine in pre-specified subgroups

Age <65 years ≥65 years

Sex Male Female

Beta-blockers No Yes

Aetiology of heart failure Non-ischaemic Ischaemic

NYHA class NYHA class II NYHA class III or IV

Diabetes No Yes

Hypertension No Yes

Baseline heart rate <77 bpm ≥77 bpm

Test for interaction

P = 0.029

1.5 1.0 0.5 Hazard ratio

Favours ivabradine Favours placebo

Swedberg K, et al. Lancet. 2010;376:875-85

NS

NS

NS

NS

NS

NS

NS

n=6505

Ivabradine reduced the composite of CV death

and hospitalisation for worsening HF in patients with a

heart rate >77bpm

Coralan Approved Product Information

n=3357

Treatment effect on the primary composite endpoint, its components

and secondary endpoints in patients with a heart rate >77bpm

Coralan Approved Product Information

Ekman et al EHJ 2011: 32; 2395

<72

72 to <75

75 to <80

80 to <87

≥87

No BB BB<25% BB ≥100%

Beta-blocker category

Baseline

HR category (bpm)

HR reduction according to B-blocker dose and HR category

HR reduction from

baseline to 28 days

with ivabradine*

(bpm)

BB 25-50% BB 50-100%

*Placebo corrected

No impact of BB dose

on HR reduction with ivabradine

Impact of baseline

HR on HR reduction

with ivabradine

Swedberg K, et al. J Am Coll Cardiol. 2012. n=6398

Recommended in Australian Heart Failure guidelines

TGA indication stipulates HR >77bpm

Adapted from reference 1 & 2. 1. Thollon C, et al. Br J Pharmacol. 2007;150:37-46. 2. DiFrancesco A, et al. Drugs. 2004;64:1757-1765.

3. Coralan Approved Product Information *Please refer to Coralan Approved Product Information before prescribing.

In the sinus node, the If current determines the slope of diastolic

depolarisation, the frequency of action potentials & thus heart rate1,2

Ivabradine - The first selective heart rate lowering agent 1,2,3

Surgery

• STITCH

• CABG

• Valve surgery

Management

• Device therapy

– ICD for poor LV function

– Cardiac resynchronisation therapy + ICD

• LV assist devices

• Cardiac transplantation

Cardiac resynchronisation therapy

Treatment Approach for the Patient with Heart Failure

Stage A

At high risk, no structural disease

Stage B

Structural heart disease,

asymptomatic

Stage D

Refractory HF requiring

specialized interventions

Therapy

• Treat Hypertension

• Treat lipid

disorders

• Encourage regular

exercise

• Discourage alcohol

intake

• ACE inhibition

Therapy

• All measures under

stage A

• ACE inhibitors in

appropriate

patients

• Beta-blockers in

appropriate

patients

Therapy

• All measures under

stage A

Drugs:

• Diuretics

• ACE inhibitors

• Beta-blockers

• Digitalis

• Dietary salt

restriction

Therapy

• All measures under

stages A,B, and C

• Mechanical assist

devices

• Heart

transplantation

• Continuous (not

intermittent) IV

inotropic infusions

for palliation

• Hospice care

Stage C

Structural heart disease with prior/current

symptoms of HF

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001

AF rate control

Effect of stopping

alcohol excess

The Vicious Cycle of Heart Failure Management

Chronic HF

MD’s Office

Emergency Room

Hospitalization

SOB

Weight

PO Lasix IV Lasix or

Admit

Diurese & Home

HFpEF

• Common – + 50%

• Increases with age,

• Commoner in women

• Commoner with history of hypertension

• Prognosis as poor as HFrEF

• Mainstay of treatment is diuretics and BP control

HFpEF

Remote monitoring

OSA & heart failure

• Commonly co-exist.

• Up to 30% of patients with heart failure have OSA

Refractory heart failure

• Sequential nephron blockade

Specific challenges

• Managing complications – AF, renal dysfunction

• Anticoagulation – Warfarin vs NOAC’s

• End-of-life care

Summary

• Heart failure is common and a large burden on healthcare

• Don’t forget the echocardiogram

• Look for reversible causes

• Fine-tune the medications

• Consider device therapy

• Involve the patient