What’s the evidence base for heart failure diagnosis & management in the guideline

updates?

Frans Rutten, general practitioner Julius Center for Health Sciences and Primary care

University Medical Center Utrecht, Netherlands

EPCCS summit Prague 2015

‘The very essence of cardiovascular practice

is recognition of early heart failure’

Sir Thomas Lewis – 1933

An iceberg!

25%

asymptomatic ventricular dysfunction

heart failure treated in primary care

heart failure treated by hospital specialists

unknown heart failure (although symptoms!)

Hoes et al. Eur Heart J 1998;19:L2-

Early detection is crucial

1. case-finding in high-risk groups (e.g. COPD, type 2 DM)

2. diagnosing / recognition in those presenting complaints

- older patients often do not visit doctors with HF complaints

“part of ageing”

- doctors often do not recognise HF at consultations

atypical presentation, co-morbidity

- patients usually presented to primary care/non-cardiologists

Example of early diagnosis: UHFO-DD study

Optimal diagnostic strategy in primary care?

• 728 suspected patients in primary care (non-acute onset)

• mean age 71 yrs

• diagnostic out-patient clinics in 8 hospitals

• diagnostic cocktail plus 6 months follow-up

• reference standard expert panel: 28% heart failure

Kelder et al. Circulation 2011; 124:2865-

example of case-finding; in type 2 diabetes

• 605 patients > 60 years

• 31% heart failure (of which 87% unknown)

• unknown heart failure: 83% HFpEF !!!

Boonman-de Winter et al, Diabetologia 2012;55:2154

A diagnostic algorithm: MICE rulereferral for echocardiography in suspected HF

Roalfe et al. Eur J Heart Fail 2012;14:1000

MICE: Male, Infarction, Crepitations, Edema

Definition of heart failure (HFrEF and HFpEF)

abnormality of cardiac structure or function

leading to

failure of the heart to deliver oxygen at a rate commensurate with the requirements of the

metabolizing tissues

Fluid overload compensation reduced oxygen delivery (‘backward failure’) adaptation (‘forward failure’)

Does wheezing fit with asthma or COPD?

35% of elderly with acute HF wheeze at initial presentation

Risk of overdiagnosing COPD

Jorge S et al. BMC Cardiovasc Disord 2007;7:16

COPD (GOLD-criteria) = Obstruction on spirometry

= FEV1/FVC <70% (or LLN)

• non-acute HF: both FEV1 and FVC decreased with 20%

• If fluid overloaded: FEV1 more reduced than FVC

• HF with increased interstitial pulmonary fluid pressure:

pulmonary obstruction with spirometry !!

reason of overdiagnosing COPD

• better: bodyplethysmography (RV/TLC)

Gueder G, et al. J Card Fail 2012;18:637-644

pitfall with spirometry if shortness of breath

Most important clinical variables for diagnosis

• History: ischaemic heart disease, type 2 DM, hypertension

• Symptoms: breathlessness, fatigue, ankle oedema

• More typical symptoms: orthopnoea/parox noct dyspnoea

• Signs:

fluid: pulmonary crepitations, ankle oedema, JVP

adaptation: displaced apex beat, tachycardia, murmur

Palpation apical impulse

(NTpro)BNP tests: why difference in exclusionary cut points in acute vs. non acute setting?

Differences in prior change (prevalence)

Difference in severity of disease

different patient profile

Other

Positive predictive values

Negative predictive values

Sensitivity

Specificity

BNP in 1872 patients suspected of non-acute HF

NT-proBNP in 1297 patients suspected of non-acute HF

Causes for elevated NTproBNP

acute dyspnoea slow onset dyspnoea

• ACS age >75 jaar

• pulmonary embolism atrial fibrillation

• acute renal failure renal impairment

• pulmonary arterial hypertension LVH

• sepsis severe COPD

Conclusions diagnosis and case-finding

• signs & symptoms & history: more accurate than often believed

• So…use eyes, ears, hands, and stethoscope

• Wheezing doesn’t mean COPD or asthma! Do not refer wrong!

• additional tests: natriuretic peptides most valuable

• Tools: diagnostic score / algorithm available for daily practice

• Still barriers to echocardiography in primary care

• Spirometry only when stable, euvolemic

• High risk patients (e.g. type 2 DM, COPD) profit from case-finding

Pre-hospital treatment options in suspectected AHF

• furosemide 40 mg iv

• when oxygen saturation <92%: 2 l/min oxygen in COPD

• when severe dyspnoea/agitation: 5 mg morphine slowly iv

• when systolic > 110 mmHg: nitroglycerine sublingual

McMurray JJ, et al. Eur J Heart Fail. 2012;14:803-869

Biological Concept: Rationale for Dual

Acting Therapy with ARNI: LCZ696

NEP iVasodilation

$Blood pressure$ Sympathetic tone$Aldosterone levels

NatriuresisDiuresis

$Blood pressure

ValsartanVasodilation

$Sympathetic tone$Aldosterone levels$Sodium retention$Cellular growth

Biological Concept

Inactive fragments

NEP

Diuresis/NatriuresisANP/BNP

Blood Vessels VasoconstrictionVasodilation

Ang IIAng I FragmentsNEP

Comparison and results PARADIGM 2014

• Angiotensin-Neprilysin inhibition (ARNI) vs. enalapril (10 mg b.d.)

• In 8442 symptomatic patients HFrEF, LVEF<40%, BNP >150 pg/ml, on ACE-I or ARB, mean age 63.8 yrs, 21% females

• Stopped early, FU 27 months

• Background medication:

Diuretics 80%

BB 93%

MRA 55%

• Composite mortality from CV cause + hospitalization for HF

• Composite : 21.8% vs. 26.5% (ARR 4.7%; RRR 20%)

• All cause mortality: 17.0% vs. 19.8% (HR 0.84; NNT 32)

Can we supplant ACE-I or ARB by ARNI?

• In those who showed to be tolerant to ACE-I or ARB

• Run in; 20% dropped out

• As to be expected: not many adverse effects

• Enalapril 10 mg b.d not equipotent to valsartan 160 mg in LCZ696

• One swallow doesn’t make a summer..

Drug treatment of HFpEF

Diuretics if fluid overloaded: symptom relieve

Blood pressure management

PEP-CHF ACE-inhibitor

I-PRESERVE ARB

ALDO-DHF/TOPCAT MRA

PARAMOUNT ARNI

Ongoing:

PARAGON ARNI vs valsartan

TOPCAT

HR = 0.89 (0.77 – 1.04)

p=0.138

TOPCAT: Primary Outcome

Spironolactone

Placebo

351/1723 (20.4%)

320/1722 (18.6%)

Pitt B, et al. New Engl J Med. 2014;370:1383-92

TOPCAT

HR=0.82 (0.69-0.98)

HR=1.10 (0.79-1.51)

Interaction p=0.122

US, Canada, Argentina, Brazil

Russia, Rep Georgia

Placebo:280/881 (31.8%)

Placebo:71/842 (8.4%)

Interaction by region !!

Denmark 2012

Similar results with COACH-2 in the Netherlands

Similar results with COACH-2 in the Netherlands

The Netherlands 2012

Mean age 82.3 years

In last year: 0.4 times visits to cardiology OPC

12.1 home visits by GP

55.9% died at home or home for the elderly

32.6% died in hospital (in total 5.8% on cardiology ward)

Cause of death:

28% sudden death

23% progressive HF

20% cancer

29% others

Death

High

LowMany years

Function

Death

High

LowMonths or years

Function

Organ failure

6

Acute2 7

Death

High

LowWeeks, months, years

Function

5GP has 20

deaths per

list of 2000

patients

per

year

Primary care can deliver end of life care for all in need

Individual disease trajectory heart failure

Conclusions treatment/palliative care

• Treatment should start upstream

• HFrEF; (diuretics), ACE-i/ARB, beta-blockers, MRA

• ARNI’s: upcoming for HFrEF

• HFpEF patients will ‘love you” if you titrate diuretics adequately

• Consider spironolacton, certainly if blood pressure is high

• Cooperative care is a good option

• Last year of life/palliative care: the GP is ‘in the lead’