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Management in patients with Acute Decompensated Heart Failure

Dr Elaine ChauHK Sanatorium & Hospital, Hong Kong

3 August 2014

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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)

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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

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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

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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)

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Assessment of patient with suspected acute HF

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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

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Causes of acute heart failure

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Causes of acute heart failure

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Evidence of severely decompensated HF, including:• Hypotension• Worsening renal function• Altered mentationDyspnea at rest• Typically reflected by resting tachypnea• Less commonly reflected by oxygen saturation <90%Hemodynamically significant arrhythmia• Including new onset of rapid atrial fibrillationAcute coronary syndromes

Hospitalization recommended

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Hospitalization should be consideredWorsened congestion• Even without dyspnea• Typically reflected by a weight gain ≥5 kilogramsSigns and symptoms of pulmonary or systemic congestion even in the absence of weight gainMajor electrolyte disturbanceAssociated comorbid conditions• Pneumonia• Pulmonary embolus• Diabetic ketoacidosis• Symptoms suggestive of transient ischemic accident or strokeRepeated ICD firingsPreviously undiagnosed HF with signs and symptoms of systemic or pulmonary congestion

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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

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Current IV Treatments for Acute Heart Failure

• Diuretics

• Other agents (inotropes)• ß-receptor agonists

(dobutamine, dopamine)• PDE inhibitors (milrinone)

• Nitrates and/or any other IV vasodilators

Preload

Contractility

Afterload

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Management of acute pulmonary oedema

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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)

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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

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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

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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

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Management of acute pulmonary oedema

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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 end-organ dysfunction, low-output syndrome, symptomatic hypotension despite adequate filling pressure or unresponsive to iv vasodilators)

• Continuous monitoring of cardiac rhythm• Frequent blood pressure monitoring

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Vasodilators

For afterload reduction (by decreasing myocardial oxygen demand and improving forward flow)

•i.v. nitroglycerin (10-20mcg/min initially; increasing by 5-20 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/)

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i.v. vasodilators to treat acute heart failure

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Positive inotropes or vasopressors for acute HF

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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

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Inotropic drugs

Gs Gi

β-receptor

ATP cAMP (active)

rise in intracellular calcium

Dobutamine

AMP (inactive)

PDE

Na+/Ca2+

exchangerNa+/K+exchanger

[Ca2+]

[Na+]

[K+]Digoxin

Milrinone

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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

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Management of acute pulmonary oedema

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Treatment of patients with acute heart failure

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Treatment of patients with acute heart failure

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Treatment of patients with acute heart failure

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Treatment of patients with acute heart failure

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Levosimendan

Clinical Effect Ideal Agent LevosimendanPDE Inhibitors Dobutamine

Cardiac Output

Heart Rate

Blood Pressure

Oxygen Demand

Arrhythmogenic Potential

Cardiac Filling Pressure

or

Tachyphylaxis

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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)

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Levosimendan• Calcium sensitizer with inodilatory properties (PDE-

III 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

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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

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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 (0.1-0.2mcg/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

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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

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Conclusions fromREVIVE 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 BNPMortality was numerically greater vs placebo but lower vs dobutamineAF was increased during 3- to 6-month FU periodVT was increased vs placebo but not increased vs dobutamine

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Nesiritide• B-type natriuretic peptide counter-regulation of renin-angiotensin-

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

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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)

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NesiritideExpert 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

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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 NT-

proBNP, 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

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Goals of treatment in acute heart failure

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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