Download Document

Management in patients with Acute
Decompensated Heart Failure
Dr Elaine Chau
HK Sanatorium & Hospital, Hong Kong
3 August 2014
1
Acute decompensated heart failure
• Acute heart failure defined as onset of symptoms or signs
of heart failure in a patient with/without prior history of
heart failure
•Heterogeneous group of disorders leading to worsening of
left ventricular function
•About 50% of patients with HF have preserved systolic
function (LVEF > 50%)  diastolic dysfunction (HF-PEF)
2
Causes of acute HF due to LV dysfunction
• Primary cardiac – cardiomyopathy, myocarditis, ischaemia,
arrhythmia, valvular dysfunction, pericardial syndrome
• Pressure overload – hypertensive urgency or emergency
• Volume overload – sodium or volume load, renal or
hepatic dysfunction
• High output – shunt, anaemia, septicaemia, thyroid
disease
• Other – inflammation or infection, major surgery, lack of
compliance with heart failure medications, substance
abuse
3
Signs and symptoms
• Prior history of HF or myocardial injury
• Dyspnoea on exertion, orthopnoea, paroxysmal nocturnal
dyspnoea
• Fatigue
• Increasing oedema, weight or abdominal girth
• Signs:
•Elevated JVP
•Peripheral oedema or ascites
•Rales, hypoxia or tachypnoea
•Tachycardia, arrhythmia
4
Evaluation of heart failure
• ECG, CXR
• echocardiogram
• blood tests
- BNP, NT-proBNP or MR-proANP (to differentiate
dyspnoea due to HF from dyspnoea of other causes)
• Evaluate possibility of coronary artery disease – coronary
angiography
• Evaluate possibility of myocardial disease –
endomyocardial biopsy (e.g. myocarditis, infiltrative heart
disease, anthracycline toxicity in cancer patients)
• Functional capacity (6-min walk, exercise testing with
measurement of peak oxygen uptake)
5
Assessment of patient with suspected acute HF
6
Precipitating factors
• Atrial fibrillation
• Other arrhythmias (eg, atrial flutter, other
supraventricular tachycardia or ventricular tachycardia)
• Exacerbation of hypertension
• Myocardial ischemia/infarction
• Exacerbation of pulmonary congestion
• Anaemia
• Thyroid disease
• Significant drug interactions
7
Causes of acute heart failure
8
Causes of acute heart failure
9
Hospitalization recommended
Evidence of severely decompensated HF, including:
• Hypotension
• Worsening renal function
• Altered mentation
Dyspnea at rest
• Typically reflected by resting tachypnea
• Less commonly reflected by oxygen saturation <90%
Hemodynamically significant arrhythmia
• Including new onset of rapid atrial fibrillation
Acute coronary syndromes
10
Hospitalization should be considered
Worsened congestion
• Even without dyspnea
• Typically reflected by a weight gain ≥5 kilograms
Signs and symptoms of pulmonary or systemic congestion even in the absence
of weight gain
Major electrolyte disturbance
Associated comorbid conditions
• Pneumonia
• Pulmonary embolus
• Diabetic ketoacidosis
• Symptoms suggestive of transient ischemic accident or stroke
Repeated ICD firings
Previously undiagnosed HF with signs and symptoms of systemic or pulmonary
congestion
11
Treatment goals for patients
admitted for ADHF
•
•
•
•
•
•
•
•
•
Improve symptoms, especially congestion and low output symptoms
Optimize volume status
Identify etiology
Identify precipitating factors
Optimize chronic oral therapy
Minimize side effects
Identify patients who might benefit from revascularization
Educate patients concerning medications and self-assessment of HF
Consider and, where possible, initiate a disease management
program
12
Current IV Treatments for
Acute Heart Failure
• Diuretics
Preload
• Other agents (inotropes)
• ß-receptor agonists
(dobutamine, dopamine)
• PDE inhibitors (milrinone)
Contractility
• Nitrates and/or any other IV
vasodilators
Afterload
13
Management of acute pulmonary
oedema
14
Fluid overload
•
•
•
•
•
i.v. loop diuretics
Daily body weight, intake / output balance
Daily RFT/electrolytes (K, Mg)
Low sodium diet(2g daily)
Fluid restriction (<2L/day)for patients with moderate hyponatraemia
(congestion fails to improve)
• Increased doses of loop diuretics or continuous infusion of loop diuretic
• Add second type of oral diuretic (metolazone or spironolactone) or i.v.
(chlorothiazide)
15
Diuretics
For relief of congestion in patients with elevated filling
pressures (PCWP > 25mmHg) due to volume overload
•Loop diuretics (e.g. frusemide) – when high doses are
required, continuous infusion may have benefits over bolus
dosing
• add metolazone to potentiate natriuresis
• spironolactone to stem potassium losses
• acetazolamide to correct hypochloremic metabolic
acidosis
16
Ultrafiltration
UNLOAD (Ultrafiltration versus Intravenous Diuretics for
patients Hospitalized for Acute Decompensated Heart
Failure)
• 200 patients with acute decompensated HF
•Peripheral venovenous ultrafiltration compared with
diuretics alone
•Improved weight loss at 48 hours
•Decreased need for vasoactive drugs
•Reduced rate of readmission to hospital at 90 days
Costanzo MR et al. J Am Coll Cardiol 2007; 49: 675-683
17
Respiratory therapies
•Supplementary oxygen
•Short-term positive pressure ventilation, e.g. CPAP
(continuous positive airway pressure) or BiPAP (bilevel
positive airway pressure)
•(in acute MI with respiratory distress) invasive mechanical
ventilation
18
Management of acute pulmonary
oedema
19
IV Vasodilators / Inotropes
• (absence of hypotension) i.v. nitroglycerin, nitroprusside or nesiritide
• iv vasodilators and diuretics recommended for rapid relief of acute
pulmonary oedema and hypertension
• i.v. inotropes (milrinone or dobutamine) to improve symptoms and
improve end-organ function in patients with advanced heart failure
(LV dilatation ,reduced LVEF, diminished peripheral perfusion or endorgan dysfunction, low-output syndrome, symptomatic hypotension
despite adequate filling pressure or unresponsive to iv vasodilators)
• Continuous monitoring of cardiac rhythm
• Frequent blood pressure monitoring
20
Vasodilators
For afterload reduction (by decreasing myocardial oxygen
demand and improving forward flow)
•i.v. nitroglycerin (10-20mcg/min initially; increasing by 520 mcg/min every 3-5 min as BP allows)
•i.v. morphine (bolus 2-4mg)
•i.v. nitroprusside (continuous infusion of 0.3mcg/kg/min;
titrate rapidly to desired BP; max dose 10mcg/kg/)
21
i.v. vasodilators to treat acute heart
failure
22
Positive inotropes or vasopressors for acute HF
23
Inotropes
Vasodilating inotropes: for short-term use in patients with
significantly impaired cardiac output
•Dobutamine 2-20mcg/kg/min
•Milrinone 0.125-0.75mcg/kg/min (renal adjustment
necessary)
Vasopressor inotropes: for patients with hypotension
(avoid in pure HF with high systemic vascular resistance)
•Dopamine 1-50mcg/kg/min
•Norepinephrine 0.01-0.4mcg/kg/min
24
Inotropic drugs
Dobutamine
Digoxin
[K+]
β-receptor
Gs Gi
ATP
Na+/K+exchanger
[Ca2+]
[Na+]
Na+/Ca2+
exchanger
cAMP (active)
rise in intracellular
calcium
PDE
Milrinone
AMP (inactive)
25
Haemodynamic monitoring
• Routine invasive haemodynmaic monitoring not recommended
• Invasive haemodynamic monitoring to be considered in
• Patient refractory to initial therapy
• Patient whose volume status and cardiac filling pressures are
unclear
• Patient with clinically significant hypotension (SBP <80mmHg) or
worsening renal failure during therapy
• Patient in whom documentation of an adequate haemodynamic
response to the inotropic agent is necessary when chronic
outpatient infusion is being considered
26
Management of acute pulmonary
oedema
27
Treatment of patients with acute heart
failure
28
Treatment of patients with acute heart
failure
29
Treatment of patients with acute heart
failure
30
Treatment of patients with acute heart
failure
31
Levosimendan
Clinical Effect
Ideal Agent
Dobutamine
PDE Inhibitors
Levosimendan
Cardiac Output
Heart Rate
or
Blood Pressure
Oxygen Demand
Arrhythmogenic Potential
Cardiac Filling Pressure
Tachyphylaxis
32
Levosimendan for treatment of
acute decompensated heart failure
Dual mechanism of action:
1) Calcium sensitization (improves cardiac contractility without
concomitantly increasing myocyte oxygen consumption)
2) potassium-ATP channel opening (results in vasodilation,
improving blood flow to vital organs)

33
Levosimendan
• Calcium sensitizer with inodilatory properties (PDEIII inhibitory activity)
• Pharmacokinetics:
– Onset of action 10-20 min
– Duration of action – haemodynamic effects
maintained for at least 24 hours after
discontinuation of a 24-hour infusion
– Excretion : liver
• Adverse reaction: Dose-related hypotension
• No significant conduction disturbance or
proarrhythmia
34
Levosimendan
• LIDO (Lancet 2002; 360:196-202)
- Benefit & safety better than standard inotrope in
ADHF
• RUSSLAN study (Eur Heart J 2002;23:1422-32)
– Safe & effective for patients with LV failure
complicating acute MI
• CASINO (Eur J Heart Fail 2004;6:673-6)
– Clear mortality benefit in favour of levosimendan
compared with dobutamine in class IV CHF patients
• REVIVE I trial (Crit Care 2004;8(suppl 1):P88)
– Levosimendan reduces length of intensive and
hospital day in patient with acute decompensated HF
35
Levosimendan for treatment of
acute decompensated heart failure
REVIVE II (Randomized Multicenter Evaluation of Intravenous
Levosimendan Efficacy Study)
(AHA Scientific Sessions 2005 Late Breaking Clinical Trials II)
 600 patients, 103 sites
 ADHF, dyspnoea at rest despite iv diuretics, LVEF <35%
 Levo bolus (6-12 mcg/kg) + 24-hour infusion (0.10.2mcg/kg/min) vs placebo
 After 5 days, more Levo patients improved (19.4% vs 14.6%),
fewer Levo patients worsened (19.4% vs 27.2%)
 Significant BNP reduction in Levo arm at 24 hours & 5 days
 No difference in mortality at 90 days
36
Levosimendan for treatment of
acute decompensated heart failure
SURVIVE (Survival of Patients with Acute Heart Failure in Need
of Intravenous Inotropic Support Study)
(JAMA 2007; 297:1883-1991)
 1327 patients, 75 sites
 ADHF, LVEF <35%, clinical requirement for iv inotropic
therapy
 Levosimendan bolus + infusion vs dobutamine
 Reduction of mortality by 28% at 5 days and of 14% at 31
days in in Levo arm
 Effect greatest (42% reduction at 5 days) in patients with
previous heart failure
 Statistically non-significant but consistently lower mortality
at 6 months with Levo
37
Conclusions from
REVIVE II and SURVIVE
Levosimendan represents an effective alternative to current
therapies for ADHF
 Short-term improvement in symptoms and clinical course,
associated with marked reduction in BNP
Mortality was numerically greater vs placebo but lower vs
dobutamine
AF was increased during 3- to 6-month FU period
VT was increased vs placebo but not increased vs
dobutamine

38
Nesiritide
• B-type natriuretic peptide  counter-regulation of reninangiotensin-aldosterone system  stimulating cGMP  smooth
muscle cell relaxation
• Vasodilatory properties, natriuretic effects, neurohormonal
antagonism
VMAC (JAMA 2002; 287(12):1531-1540)
• PAP, PCWP; no tachyphylaxis/tolerance (unlike nitroglycerin)
PRECEDENT (Am Heart J 2002; 144(6):1102-1108)
• Nesiritide had no significant effect on HR or ventricular arrhythmias
• Dobutamine but not nesiritide was proarrhythmic
39
Nesiritide
• 2001 FDA approved for treatment of acute
decompensated heart failure
• Pooled analysis of randomized controlled trials 
risk of death at 1 month (Sackner-Bernstein et al,
JAMA 2005;293:1900-1905) & worsening renal
function (Sackner-Bernstein et al, Circulation
2005;111:1487-1491)
40
Nesiritide
Expert panel (Braunwald et al 2005)
• Use of nesiritide should be limited to patients
presenting to hospital with acutely decompensated
CHF
• Should not be used to replace diuretics
• Not for
• Intermittent outpatient use
• Scheduled repetitive use
• Improvement of renal function
• Enhancement of diuresis
41
Serelaxin
• Recombinant human relaxin-2 (vasoactive peptide hormone)
• RELAX-AHF (randomised placebo-controlled trial – Serelaxin for
treatment of acute heart failure)
• Patients with dypsnoea, congestion on CXR, increased BNP or NTproBNP, mild-mod renal insuffuciency, SBP >125mmHg
• Standard care plus 48-hour infusion of placebo or serelaxin
(30mcg/kg per day) within 16 hours from presentation
• Tx of acute HF with serelaxin was associated with
– Dyspnoea relief (as measured by visual analogue scale area
under the curve / VAS AUC to day 5)
– Reduced 180-day mortality
• No effect on re-admission to hospital
Teerlink JR et al - Lancet 2013; 381(9860):29-39
42
Goals of treatment in acute heart failure
43
Discharge criteria for HF patients
• Exacerbating factors addressed
• At least near optimal volume status achieved
• Transition from intravenous to oral diuretic successfully
completed
• Patient and family education completed
• At least near optimal pharmacologic therapy achieved
• Follow-up clinic visit scheduled, usually for 7-10 days
44