Management of Heart Failure – from diagnosis to the grave

Richard Lawrance Consultant Cardiologist - WMH

55y man Breathless Ex tolerance 100yds on flat,

limited by SOB No chest pain ‘Borderline hypertension’ Obst sleep apnoea Diabetic O/E

– Overweight + – BP154/88, P 90 reg – 4th HS – JVP – obscured by fat – Oedema to mid thighs

Case Presentation

H

H

Hypertension

HF Diabetes

….just a personal perspective!

H

http://ironman.com/�

…..from diagnosis to the grave

• Can we predict those who might develop HF? • If we can would any intervention help?

STOP-HF Investigators

St. Vincent’s / St. Michael’s Hospitals and Collaborative GP Group Dublin, Ireland

The Saint Vincents Screening To Prevent Heart Failure (STOP-HF) Study

A Multicentre, Prospective, Randomised, Controlled Trial of

Natriuretic Peptide Based Screening And Collaborative Care To Reduce The Prevalence of Left Ventricular Dysfunction

and Heart Failure

STOP-HF Inclusion / Exclusion

• Entry Criteria (> 40yrs) with Hypertension Hyperlipidemia Diabetes Vascular disease Arrhythmia Obesity

• Primary End Point – Prevalence of heart failure (hospitalized) and asymptomatic left ventricular dysfunction

• Systolic Dysfunction: LVEF < 50% • Diastolic Dysfunction: E / e prime > 15

• Secondary End Point – Hospitalization for Cardiovascular Events (Time to event and Event rate)

• Heart Failure, Arrhythmia, Myocardial Infarction, Unstable angina, CVA, TIA, Peripheral Thrombosis, PE

•Excluded

– Known LVSD or HF – Life-threatening illness – Refusal / inability to give

informed consent

Routine PCP care •Annual BNP not available to clinicians •At least annual review by PCP •Cardiology review only if requested by PCP

NP-directed care In addition to routine PCP care •Annual BNP in all

If BNP >50pg/ml at any time •Shared-care

Cardiology review Echo-Doppler Other CV investigations CV nurse coaching Regular Cardiology follow-up

STOP-HF Intervention

15.5 9.9

6.2

2.7

3.8

2.7

3.8

1.4

11

5.5

0

5

10

15

20

25

30

35

40

45

Control Intervention

Num

ber o

f eve

nts

per

1,00

0 pa

tien

t yea

rs Stroke/TIA

PE/DVT MI Heart Failure Arrhythmia

N=71 (10.5%) N=51 (7.3%)

Event Rate OR 0.54 p=0.001 vs. Control

Endpoint – MACE Event Rate

CONCLUSION: Reduced the rates of left ventricular dysfunction, heart failure, and emergency hospitalizations for major cardiovascular events with NP-based screening

55y man Breathless Ex tolerance 100yds on flat,

limited by SOB No chest pain ‘Borderline hypertension’ Obst sleep apnoea Diabetic O/E

– Overweight + – BP154/88, P 90 reg – 4th HS – JVP – obscured by fat – Oedema to mid thighs

Case Presentation Going back to our case

Clinical Case Presentation

• Initial investigations • CXR and ECG • Basic spirometry normal • Echo showed ‘mild concentric

LVH, EF 55%, dilated LA 48mm, mild to moderate MR

Mineralocorticoid Receptor Antagonists

Mineralocorticoid Receptor Antagonists in LV systolic dysfunction

• RALES Study NYHA class III / IV Significantly reduced all-cause mortality in spironolactone group compared with

placebo (35 vs. 46%, relative risk reduction 30%, p<0.001) Significantly more gynaecomastia with spiro (p<0.001)

• EPHESUS Study HF post-MI Significantly reduced all-cause mortality with Epleronone, RRR 15% Significantly reduced CV death / hospitalisation, RRR 13%

• EMPHASIS Study NYHA II patients Significant reduction in CV death / HF hospitalisations with epleronone, (25.9%

vs 18.3%, RRR 37%) 32% RRR in death for worsening HF 42% RRR in HF hospitalisations

RATIONALE - HF mortality remains high -RAS inhibition works in HF - Aliskiren inhibits RAS so it has to be good in HF pts, doesn’t it?

• Assess efficacy and safety of Darbepoetin alfa treatment on mortality and morbidity in heart failure subjects with symptomatic left ventricular systolic dysfunction and anaemia

Darbepoetin alfa – glycoprotein that stimulates erythropoietin, a hormone released from the kidney that develops red blood cells and produces hemoglobin

Reduction of Events with Darbepoetin alfa in Heart Failure Trial

RED-HF Trial

Results / Conclusion

• Negative result • 2,278 pts • Hb improved • No improvement in HF admissions • Excess of thromboembolic events in treated

group • Hb is marker of poor prognosis in HF rather

than a therapeutic target

18%

45%37%

LV Function in Patients with First Admission for Heart Failure in ALLHAT

HF BY EF LEVEL N=1399

EF<40%

EF 40-49% EF>50%

>60% had EF>40%

No. at risk 510 377 313 263 216 117 771 537 447 375 314 262 885 629 513 365 230 138

Owan et al, NEJM, 2006

Survival in HF-PEF hasn’t changed

Years

Surv

ivin

g

p=0.36

1987-1991 1992-1996 1997-2001

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5

Results in Left Ventricular Hypertrophy

Causes of diastolic dysfunction? • pressure overload

Diabetes Mellitus

Diabetic foot and eye disease

Causes of diastolic dysfunction?

Causes of diastolic dysfunction?

Normal >50ml/m2 Increasing LA volume

2-ye

ar m

orta

lity

10%

50%

LA size and mortality post-MI

LA size also predicts: Heart Failure Stroke AF onset

A Practical approach to diagnosis of HFPEF

• Patient has clinical or radiographic evidence suggestive of heart failure. EF preserved (≥50% on echo)

• Major Criteria E/e’>15 Invasive haemodynamics suggestive of raised PCWP or LVEDP

• Minor Criteria Raised BNP>200 AF Raised LV mass index Raised LA volume index 8 < E/e’ > 15

To clinch diagnosis need 1 major or 2 or more minor criteria

EVIDENCE BASE FOR DIASTOLIC HEART FAILURE

HF-PEF Current treatment targets and options

• LV volume & oedema: Diuretics, salt restriction, nitrates

• Rx HTN: Diuretics, CCB, BB, ACEI, ARB

• Reverse LVH: Most antihypertensives

• Prevent ischemia: BB, CA, nitrates

• Reduce HR, prevent AF: BB, rate lowering CA, ARB

• Bradycardia: Atrial Pacing

• Enhance relaxation: No current treatment

• Prevent vascular events: ACEI, ARB, BB

What is the evidence?

Effects of verapamil in “ diastolic heart failure” 20 patients - CHF > 3 months, LVEF >0.45, abnormal PFR (> 2.5 EDV/sec)

Setaro et al Am J Cardiol 1990; 12: 981-6

0

2

4

6

8

1 0

1 2

1 4

1 6

1 8 B a s e l i n e P l a c e b o V e r a p a m i l

CHF score

Exercise time (minutes)

* p < 0.01 v. placebo

6.7 6.1 3.8 10.7 12.3 13.9

B P V B P V

* p < 0.01 v. placebo

Effects of propranolol in “diastolic heart failure”

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

Inci

denc

e %

n o p r o p r a n o l o l p r o p r a n o l o l

•Aronow et al, Am J Cardiol 1997; 2: 207-9

Death Death or MI

76 56 82 59

p = 0.007 p = 0.002

158 elderly patients (mean 81 yrs) with NYHA II/III CHF, prior Q-wave MI (>6 mos), and LVEF ≥ 0.40 (mean 58%)

ALDO-DHF

• Aldosterone Receptor Blockade in Diastolic Heart Failure trial, Patients, all NHYA 2, fit enough to cycle and with ‘good renal

function’ received spironolactone for a year benefited with significantly improved diastolic function and

ventricular remodeling as well as reduced levels of natriuretic peptides

no apparent effect on NYHA class, exercise capacity, or patient quality of life in the trial. HOWEVER: Aldo-DHF is a study of early-phase diastolic dysfunction, very

early diastolic heart failure many of the trial's patients had relatively low BNP levels Virtually no mortality in the trial Hopefully, the TOPCAT study will reveal more

Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and Clinical Status in Heart

Failure with Preserved Ejection Fraction (RELAX)

• Phosphodiesterase type-5 (PDE-5) metabolizes nitric oxide (NO) and natriuretic peptide (NP) generated cGMP

• If PDE-5 is activated in HF; may limit beneficial NO and NP actions in the heart, vasculature and kidney

• Viagra in stiff hearts – no clinical benefit seen

If there’s not much effective treatment, how can I help you die well? Palliative care

for HF

Case Presentation

• “It is easier to die of Cancer than Heart or Renal

failure” John Hinton (Medical Attending Physician) 1963

Clinical Features

• Similarities to Cancer Dyspnoea Cachexia/weight loss Lethargy/poor mobility Pain Anxiety & depression Insomnia & confusion

Postural

Hypotension Jaundice More infections Polypharmacy Fear of the future

O’Brien et al. BMJ 1998

Clinical Features

Differences From Cancer More oedema Predicting death more difficult Mistaken belief condition more benign than

cancer No local pressure effects Less anaemia

Experience of Patients

• Lung Cancer Clearer trajectory – able

to plan for death Initially feel well but told

you are ill Good understanding of

diagnosis and prognosis Relatives anxious Swinging between hope

and despair

• Cardiac Failure Gradual decline, acute

deterioration, sudden death Feel ill but told you are well Little understanding of

diagnosis and prognosis Relatives isolated and

exhausted Daily grind of hopelessness

(Murray 2002)

Experience of Patients

• Lung Cancer Cancer takes over life Treatment dominates life Feel worse on treatment Financial benefits

accessible Services available in the

community Care prioritised as

“cancer” or “terminal”

• Cardiac Failure Much morbidity Shrinking social world Feel better on treatment Less access to financial

benefits Services less available in

the community Less priority as “chronic

illness”

Prognostication

• Very difficult to prognosticate…would I be surprised if……??

• Markers of poor prognosis (< 6 months) Sodium:

mean of 164 days if < 137, 373 days if > 137 Liver failure, renal failure, delirium Unable to tolerate ACE-I due to bp NYHA Class 4 EF < 20% Frequent hospitalisations Cachexia

(Hauptman 2005, Taylor 2003, Ward 2002

Heart Failure: New Ideas and Old Misconceptions

• New Ideas

• Relaxation or diastolic function important

• This can be assessed on Echo

• Left atrial volume index, LV mass and E/e’ will all start to appear on echo reports – these all predict future events

• Diuretics / spironolactone and Ca-

blockers may be of some use

• Uncertain role of ACE-I / ARB

• Watch this space for other potential Rxs

• Old Misconceptions

• It’s not all about Ejection Fraction

• Heart failure can be present even if EF is normal

• There are more chambers in the heart

than just the LV!