Transcript Café Cardiologiqué Heart Failure

Café Cardiologiqué
18th December 2013
Heart Failure
Andrew Vanezis
PhD Student and Research Fellow
Outline
• How big a problem is heart failure?
• What is heart failure?
• Causes
• Signs and Symptoms
• Investigations
• Current Therapies for Chronic HF
• Up-coming therapies / Research areas
How big a problem is it?
• ~ 900,000 people in the UK have heart failure
• Similar number have heart damage but no
symptoms
• Average age of first diagnosis = 76 with incidence
and prevalence increasing with age
• 30–40% of patients diagnosed with heart failure
die within a year but thereafter the mortality is <
than 10% per year
BHF, Leicestershire County Council, Experian, SEPHO
How big a problem is it?
• Costs the NHS ~ £1.2 billion per year, ~75 % of
which is due to repeated hospitalisations
• Some hope…6-month mortality rate ↓ from 26%
in 1995 to 14% in 2005
• In 2010/11 the emergency admission rate for
heart failure in the East Midlands was 63.2 per
100,000, significantly ↑ than England overall
(59.8 per 100,000)
BHF, Leicestershire County Council, Experian, SEPHO
What is heart failure?
• Nebulous term that describes a syndrome, not a specific
diagnosis
• Broadly speaking:
When the heart can not meet the metabolic demands
of the body, usually (but not exclusively) due to a ↓
cardiac output
Some physiology…
Some physiology…
Cardiac Output = Heart Rate x Stroke Volume
Some physiology…
Cardiac Output = Heart Rate x Stroke Volume
End Diastolic Volume – End Systolic Volume
Some physiology…
Cardiac Output = Heart Rate x Stroke Volume
End Diastolic Volume – End Systolic Volume
Preload
Myocardial contractility
Afterload
Spiral into oblivion…
• Spiral phenomenon:
Defining heart failure?
Defining heart failure?
• Systolic and Diastolic
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
• Congested and Cor Pulmonale
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
• Congested and Cor Pulmonale
• High output and Low output
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
• Congested and Cor Pulmonale
• High output and Low output
• Acute and Chronic
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
• Congested and Cor Pulmonale
• High output and Low output
• Acute and Chronic
• Forward and Backward
Defining heart failure?
• Systolic and Diastolic
• HF-PEF and HF-REF
• Left and Right
• Congested and Cor Pulmonale
• High output and Low output
• Acute and Chronic
• Forward and Backward
Symptoms
LEFT
• Decreased
exercise tolerance
• Cough
• Short of breath
lying flat
• Awaking gasping
for air
BOTH
RIGHT
• Shortness of
• Oedema (of the
Breath
extremities,
scrotum,
• Fatigue
• Changes in weight abdomen)
• Abdominal pain
Signs
LEFT
• Crackles or wheezes in
chests
• Frothy/blood stained
sputum
• Confusion
• Blue extremities
BOTH
• Fast heart rate/
irregular rhythm
• Fast breathing rate
• Valve Murmurs
related to increase
volume and pressure
RIGHT
• Oedema (leg/sacral
etc.)
• Elevated neck vein
pressure
• Enlarged liver
• Chronic venous leg
changes
• Fluid at lung bases
• Free fluid in the
abdomen
• ?Primary lung cause
Stratifying severity
• NYHA class:
I. No symptoms with ordinary activity
II. Mild symptoms (e.g. shortness of breath) and slight
limitation during ordinary activity
III. Marked limitation in activity due to symptoms, even
during less-than-ordinary activity. Comfortable only
at rest.
IV. Usually bed-bound as has severe limitations.
Experiences symptoms even at rest.
Stratifying severity
• NYHA class:
I. No symptoms with ordinary activity
II. Mild symptoms (e.g. shortness of breath) and slight
limitation during ordinary activity
III. Marked limitation in activity due to symptoms, even
during less-than-ordinary activity. Comfortable only
at rest.
IV. Usually bed-bound as has severe limitations.
Experiences symptoms even at rest.
• Detailed lifestyle questionnaires
• Objective exercise assessment e.g. 6 min walk test /
bleep test – especially VO2 max
Aetiology
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Ischaemic Heart Disease (50%)
Hypertension
Diabetes
Aortic stenosis
Congenital
Alcohol
Viral e.g. peri/myocarditis
Infiltrative e.g. amyloidosis/sarcoidosis
HIV
Non-cardiac illnesses that could affect the heart indirectly:
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Hyperthyroidism
Anaemia
Paget’s disease
Pregnancy
Diagnosis of Heart Failure
• Good clinical history and examination
• Chest X-ray
• ECG
• BNP/NT-ProBNP
• Echocardiogram
• Cardiac MRI
• Anything that elucidates aetiology!
• Other investigations if alternative
diagnosis suspected
BNP
• Peptide released by ventricles due to excessive
stretching
• NT-proBNP inactive peptide released along with
BNP but remains in body twice as long
• False + in..
• Chronic obstructive pulmonary disease,
hypertrophy of the heart, sepsis, renal failure
and old age
• False – in..
• Obesity and use of heart failure meds
Echo
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Transthoracic in first instance
Doppler flow is very useful
Mainly looking at LV size, mass and function
Ejection fraction can be assessed visually, commonly
with Simpson’s bi-planar technique which good
accuracy
• Other structural/valvular
abnormalities
Management aims
• Reduce signs and symptoms (mainly of
congestion) – Morbidity
• Prolong life – Mortality
• Some therapies target morbidity or
mortality
• Some have benefits to both
Management
• Identify and treat underlying cause
• Lifestyle changes
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Smoking cessation
Reduced salt intake
Reduced alcohol intake
Exercise
Weight loss
Education
• Psychological
• Immunisations
• Links to appropriate services e.g. cardiac rehab, heart
failure nurses, social workers etc.
• Drug therapy
• Devices
• Palliative and supportive care
Management
• Identify and treat underlying cause
• Lifestyle changes
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Smoking cessation
Reduced salt intake
Reduced alcohol intake
Exercise
Weight loss
Education
• Psychological
• Immunisations
• Links to appropriate services e.g. cardiac rehab, heart
failure nurses, social workers etc.
• Drug therapy
• Devices
• Palliative and supportive care
Ace Inhibitors
• Ramipril, Enalapril, Lisinopril,
Captopril, Perindopril
Ace Inhibitors
• Ramipril, Enalapril, Lisinopril,
Captopril, Perindopril
ACEi
Ace Inhibitors
• Mortality and Morbidity benefits
• Used in all stages of HF
• Given irrespective if high BP or not
• ↓ Angiotensin 2 effects =
• ↓ sympathetic activity and ↑ parasympathetic activity
• ↓ salt and water retention (via ↓ aldosterone, ADH and direct
effects)
• ↓ arterial vasoconstriction and hence ↓BP
• Other (proto-oncogenes, fibrosis, apoptosis)
• CONSENSUS and SOLVD trials
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The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results
of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987. 316 (23):
1429–35. 35.Jump up
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection
fractions and congestive heart failure. N Engl J Med. 1991 325 (5): 293–302.
Angiotensin Receptor 2
Blockers
• Losartan, irbesartan, candesartan
• Mortality and Morbidity benefits
• Used in all stages of HF
• No added benefit with
ACEi in combination
• Usually used if ACEi not tolerated
• Can be used first line in:
• HF post heart attack
• Chronic HF and systolic dysfunction
Beta-blockers
• Bisoprolol, metoprolol, carvedilol, atenolol
• Morbidity and mortality benefit
• Improved survival in NYHA class II to III
HF ± probably class IV
Beta-blockers
• Slow heart rate (B1 blocking effect)
therefore better pumping mechanics
• For every 5bpm ↓, relative risk of death ↓ by 18%
(McAlister FA, et al.
Ann Int Med 2009;150:784)
• ↓ Renin secretion = reduced sodium and water retention
• ↓ Angiotensin 2 production
• Other unknown affects on LV remodelling
• CIBISII and MERIT-HF trials
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CIBIS II investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS II): a randomized
trial. Lancet. 1999;353:9–13.
MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised
Intervention Trial in-Congestive Heart Failure (MERIT-HF). The Lancet. 1999. 353, 9169, 2001 - 2007
Loop Diuretics
• Furosemide, Bumetanide
• Morbidity benefits only
• Used in moderate and severe HF
• Powerful diuretics acting at loop of Henle Na+/K+/2Clcotransporters competing with CL- binding site
• Can be supplemented with other classes of diuretics e.g.
thiazide/thiazide like to improve diuresis
• Long term use can lead to renal dysfunction, worsening heart failure
• ADHERE registry
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Peacock WF et al. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute
decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9.
Aldosterone antagonists
• Spironolactone, epleronone
• Morbidity and mortality benefit
• Potassium sparing diuretic (weak)
• Acts at collecting tubules – competitive inhibitor of
aldosterone which works via Na+/K+ pumps
• Used in NYHA class III and IV
• Especially useful in MI induced HF
• Augments effect of ACEi and loop diuretics
• RALES and EPHESUS trials
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Pitt B et al . The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe
Heart Failure. N Engl J Med. 1999. 341 (10): 709–717.
Pitt B et al . The EPHESUS trial: eplerenone in patients with heart failure due to systolic
dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure
Efficacy and Survival Study. Cardiovasc Drugs Ther. 2001. 15 (1): 79–87.
Ivabradine
• Morbidity and Mortality benefits (but only one trial)
• Acts on funny channel (mixed inward Na+/K+) in sinus node
reducing the steepness of diastolic depolarization curve
• Main effects from heart rate lowering therefore used if HR still
>75 despite maximal beta blocker use
• Use in II-IV stable chronic HF with systolic dysfunction
• SHIFT trial
•
Swedberg, K et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled
study. Lancet 2010. 376, 9744, 875 - 885
Hydralazine and nitrates
• Mortality and Morbidity benefits
• NYHA II-IV HF
• Hydralazine = arterial vasodilator = ↓afterload
• Nitrate = venous vasodilators = ↓preload
• African/Caribbean origin
• May have role in Diastolic heart failure
Digoxin
• Morbidity benefits only
• Blocks Na+/K+ ATPase pump in myocytes –
eventual effect = ↑ intracellular calcium =
lengthening of phase 4 and 0 of action
potential and ↓ heart rate
• Slight ↑ pumping and slight ↓ heart rate
• Often used if concurrent atrial fibrillation
• Lots of side effects
Drugs – other issues
• Drugs often prescribed at sub-optimal
doses
• Poor concordance with many cardiac drugs
• Most research in relation to Left
Ventricular Systolic Dysfunction therefore
treatment in other forms is often
extrapolation
Cardiac Resynchronisation
Therapy
Left Ventricular Assist Devices
Cardiac Transplant
Christiaan Barnard 1967
ESC guidelines 2012 algorithm
Palliative care
Research Avenues
• New drugs
• Renin blockers
• Serelaxin
• Ularitide
• Stem cells
• Heart (multi-potent cardiac progenitor cells)
• Bone marrow mobilisation
• Re-programming non mycoytes
Research Avenues
• Gene Therapy
• SERCA2a trials Imperial College/Brompton – ongoing in naive HF
and LVAD patient
• MicroRNA
• Early days
• Much focus on muscle-specific microRNAs within MHC genes
(control myosin expression + response of the heart to stress)
• Remote Ischaemic Conditioning
• DREAM and CRIC trials
Thanks and Merry Christmas!