1. ACUTE DECOMPENSATED HEART FAILURE
University of Ottawa Medical School Curriculum
Sharon Chih MBBS, FRACP, PhD
Assistant Professor, University of Ottawa
January 13h, 2016

2. Learning Objectives
Define acute heart failure and describe its pathophysiology with reference to: impaired -contractility or ventricular filling and increased afterload.
List examples of conditions that cause left and right-sided heart failure.
Review the clinical manifestation of heart failure.
Review the treatment of heart failure with reference to: diuretics, vasodilators, inotropic drugs
Distinguish between pulmonary edema of cardiogenic vs noncardiogenic origin.

3. Management of Acute HF - Outline
Review of the clinical presentation of acute HF
Causes
Clinical signs and symptoms
Diagnosis
What are the important management strategies?
What are the important prognostic markers?
How do we use diuretics?
How and when do we use inotropes or vasodilators 3

4. Definition: Heart Failure
Condition where the heart cannot pump an adequate supply of blood at normal filling pressures to meet the metabolic needs of the body
Clinically
Reduced cardiac output
Congestion
Impaired quality of life
Reduced life expectancy
Complex syndrome in which abnormal heart function results in, or increases the subsequent risk of, clinical symptoms and signs of low cardiac output and/or pulmonary or systemic congestion”

5. Distinguish from cardiomyopathy:
Pathologic abnormality of myocardium resulting in abnormal myocardial structure - cardiac dilatation and hypertrophy
All patients with cardiomyopathy do not have HF

6. Acute vs. Chronic HF? Acute HF or Acute heart failure syndrome or ADHF
First presentation of new onset HF symptoms
Acute worsening of symptoms
Previously stable HF that has deteriorated

7. Acute vs. Chronic HF Management Management Beta blockers
Acute HF
Management
Beta blockers
ACE inhibitors / ARB
Spironolactone
ICD /CRT
Management
Symptom based
Relieve congestion
Diuretics
Improve perfusion
Inotropes
Remove precipitating agent

8. General Causes of HF Coronary artery disease Myocardial infarction
Valve disease
Idiopathic cardiomyopathy
Hypertension
Myocarditis / pericarditis
Arrhythmias
Thyroid disease
Pregnancy
Toxins (alchohol, chemotherapy)
Inherited cardiomyopathies

9. Mechanisms and Causes of HF
Impaired Contractility
Myocardial infarction
Transient ischemia
Chronic volume overload
MR/AR
Dilated cardiomyopathy
Increased Afterload AS
Uncontrolled HTN
Systolic Dysfunction
Left Sided HF
Diastolic Dysfunction
Impaired ventricular relaxation
LVH
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Transient ischemia
Obstruction of LV filling MS
Pericardial constriction or tamponade

10. Mechanisms and Causes of HF
Cardiac Causes
Left sided HF
Pulmonary stenosis
Right ventricular infarction
Right Sided HF
Parenchymal pulmonary disease
COPD
Interstitial lung disease
Chronic infections
Adult respiratory distress syndrome
Pulmonary Vascular Disease
Pulmonary embolism
Pulmonary HTN
Right ventricular infarction

11. Heart Failure: Pathophysiology
Increased contractility
Normal
Stroke volume (cardiac output) A
Heart Failure B C
-in a normal heart, cardiac output increases as a function of preload. Decreased LV contractility is characertized by a heart that is shifted downward. Point a is normal person at rest. Point B is the same person after developing systolic dysfunction. , stroke volume has fallen (decreased LV emptying) and the LVEDV has increased. This increase in EDV is compensatory (on the ascending part of the curve) because it will increase SV for the next beat. BUT further augmentation in LV filling in the heart puts patients on C – where SV is not increased but symptoms of pulmonary congestion develop
Hypotension
Pulmonary congestion
Left ventricular end diastolic pressure (volume) 11

12. Heart Failure Neurohumoral Activation
Myocardial insult
LV dysfunction
Neurohormonal Activation
Sympathetic
Renin-angiotensin
ADH
LV Remodeling
Initially restores CO and organ perfusion
Ultimately highly negative impact on ventricular function

13. Functional Classification
ACC/AHA STAGES OF HEART FAILURE
STAGE A
High risk for developing HF (diabetes, CKD, HTN)
No structural disorder of the heart
STAGE B
Structural disorder of the heart (e.g.. Previous MI)
Not yet developed symptoms of HF
STAGE C
Past or current symptoms of HF
Symptoms associated with underlying structural heart disease
STAGE D
End stage disease
Requires specialized treatment strategies
NYHA FUNCTIONAL CLASS
The ACC defined 4 stages of heart failure in the last consensus guidelines. (ref:ACC/AHA 2005 Chronic Heart Failure Guideline Update, Journal of the American College of Caridiol, 2005;46: ) This highlights the point that we should think of HF in those who are at risk (stage A and B) even before they have developed symptomatic HF. The NYHA functional classification is a well-accepted definition of exercise capacity in the setting of HF.
CLASS I
No symptoms and no limitations in physical activity
No shortness of breath when walking, climbing stairs etc.
CLASS II
Mild symptoms and slight limitation during ordinary physical activity
CLASS III
Marked limitation in activity due to symptoms (fatigue, shortness of breath) with less than ordinary activity (e.g.. Short distances or ADL’s)
CLASS IV
Severe limitation, may experience symptoms at rest
INCREASING SEVERITY OF HEART FAILURE

14. AHA Classification LV dysfunction – Natural History
Mechanism of death:
40% SCD
40% ↑CHF
20% Other
Stage A
Stage B
100
Stage C
% Survival
Stage D
Annual Mortality
<5% % % %
Risk Factors Asymptomatic-Mild Moderate Severe
Time

15. Diagnosis of HF
There is no single diagnostic test that can confirm the diagnosis of heart failure
Constellation of symptoms and signs
CXR findings
Confirmation of cardiac abnormality
Invasive hemodynamic studies
Echocardiogram
Serum BNP testing

16. Symptoms and Signs of HF
Increased filling pressures
Poor Cardiac Output
Congestion
Poor Perfusion

17. Congestion – left sided
Symptoms
Dyspnea
Orthopnea
Shortness of breath when supine
Paroxysmal nocturnal dyspnea
Acute awakening from sudden dyspnea
Fatigue
Signs
S3 gallop
Displaced apex MR
Pulmonary rales
Loud P2

18. Congestion – Right Sided
Symptoms
Peripheral edema
Abdominal bloating
Nausea
Anorexia
Signs
Elevated JVP
Hepatomegaly
Ascites
Edema

19. Evaluating the JVP
Consensus: <2 cm above the sternal angle considred normal and >4cm ASA is abnormal
/gemp/ClinicalSkills/clinskil/ year1/cardio/cardio04.htm

20. Assessing Perfusion Symptoms Signs Fatigue Confusion Dyspnea Sweating
Hypotension
Tachycardia
Cool extremities
Altered mental status
Decreased urine output/Rising creatinine
Liver enzyme abnormalities

21. Pulmonary Edema General Considerations Pathophysiology
Increase in the fluid in the lung
Generally, divided into cardiogenic and non-cardiogenic categories.
Pathophysiology
Fluid first accumulates in and around the capillaries in the interlobular septa (typically at a wedge pressure of about 15 mm Hg)
Further accumulation occurs in the interstitial tissues of the lungs
Finally, with increasing fluid, the alveoli fill with edema fluid (typically wedge pressure is 25 mm Hg or more)

22. Cardiogenic vs. Noncardiogenic pulmonary edema
Heart failure
Coronary artery disease with left ventricular failure.
Cardiac arrhythmias
Fluid overload -- for example, kidney failure.
Cardiomyopathy
Obstructing valvular lesions
Myocarditis and infectious endocarditis
Non-cardiogenic pulmonary edema - due to changes in capillary permeability
Smoke inhalation.
Head trauma
Overwhelming sepsis.
Hypovolemia shock
Acute lung re-expansion
High altitude pulmonary edema
Disseminated intravascular coagulopathy (DIC)
Near-drowning
Overwhelming aspiration
Acute Respiratory Distress Syndrome (ARDS)
Re-expansion
By drainage of a large pleural effusion with thoracentesis
Of the lung collapsed by a large pneumothorax

23. CXR Findings of Pulmonary Edema
Cardiogenic pulmonary edema
Kerley B lines (septal lines)
Seen at the lung bases, usually no more than 1 mm thick and 1 cm long, perpendicular to the pleural surface
Pleural effusions
Usually bilateral, frequently the right side being larger than the left
If unilateral, more often on the right
Fluid in the fissures
Thickening of the major or minor fissure
Peribronchial cuffing
Visualization of small doughnut- shaped rings representing fluid in thickened bronchial walls
Non-cardiogenic pulmonary edema
Bilateral, peripheral air space disease with air bronchograms or central bat-wing pattern
Kerley B lines and pleural effusions are uncommon
Typically occurs 48 hours or more after the initial insult
Stabilizes at around five days and may take weeks to completely clear
On CT
Gravity-dependent consolidation or ground glass opacification
Collectively, the above four findings comprise pulmonary interstitial edema
The heart may or may not be enlarged
When the fluid  enters the alveoli themselves, the airspace disease is typically diffuse, and there are no air bronchograms \
-cuffing – is fluid in the bronchial wall – looks like donuts
Correlates with LAP –
Normal (5-10)
Cephalizatioin 10-15, kerly b 15-20, pulmonary interstital edema 20-25, alveloar edema >25

24. cuffing
Alveolar edema
Kerley B

25. Clinical Presentation of Acute HF
Gradual worsening of symptoms
-less pulmonary congestion and more edema or weight gain
->70% ADHF is worsening chronic HF
-50% of these patients may have SBP>140
Hypertension and acute pulmonary edema
10-20%
60-80%
Hypotension and markedly low CI
<10%
Symptoms are the most sensitive method for diagnosing HF but can vary. Orthopnea and PND are the most specific, but other symptoms have ssensitivity ranges of 23-66% with specificity of 52-81%, 80% of pts may not have pulmonary rales,
hTN and PE –increased sympathetic tone leads to redistribution of fluides to the pulmonary circulation. These patients are older and more likely to be female
Shock – manifested by cool extremities, end organ hypoperfusion, and overt pulmonary edema (3%) or shock (1%)
ADHERE data suggests that 50% of ADHF pts have normal or elevated BP on admission – but most of these also have LV systolic dysfn
-clues to HF with normal LVEF- wide pulse pressure more important than absolute SBP alone, -also tend to be women, older HTN and poor renal function 25

26. Presentation – Symptoms and Signs
Patient profile
Older - median 75y.o
Female ~50%
HFpEF ~50%
Comorbidities common: AF, DM, CKD
Dyspnoea 70-90%
Other: oedema, fatigue, subtle
Young: abdo pain, nausea, anorexia
Old: confusion and lethargy
JVP most sensitive
Estimate of left sided filling pressures (PCWP)
R = 0.64 for JVP and PCWP
Dissociation b/w JVP and PCWP in lung disease, obesity, PE, RV infarct
Poor sensitivity: rales, oedema, S3
Majority hypertensive
50% SBP >140 mmHg; 45% SBP 90 – 140 mmHg; 5% SBP <90 mmHg
Registry data
US: ADHERE and OPTIMIZE HF
Europe: Euro HF
HFpEF 60-90d post-discharge morbidity/mortality similar to HFrEF
R=0.64 ie ~40% of PCWP variability due to variability in RA pressure
Pulmonary findings (eg. Rales) less pronounced in decompensated CHF due to compensatory changes (eg lymphatic hypertrophy with increased capacitance) allowing accomodation of a high PCWP

27. Predictors of Adverse Outcome During Acute HF
Clinical
Hypotension (SBP <100)
Older age
Ischemic etiology
Recurrent hospitalisations
NYHA IV (>90 days)
Laboratory
Renal dysfunction (Cr >220)
Anemia (acute or chronic)
Hyponatremia (Na <132)
EF<40%
Elevated troponin or BNP (>500)

28. ADHF Treatment Goals Relieve symptoms: congestion and low out-put
Optimise volume status
Identify aetiology
Identify precipitating factors
Initiate and optimise chronic oral therapy
Minimise side effects
Educate patient/family: medications and self assessment
Goal of therapy is to relieve symptoms, for most congestion +/- low out-put, and initiate management to improve cardiac function
Focussed on prevention rather than treatment ie limitation of therapy
Very few controlled trials in ADHF. Available data limited by:
Predominant inclusion of pts with systolic dysfunction. ADHERE registry: ~50% of ADHF had preserved EF
Symptoms and not mortality as endpoints
HFSA guidelines: Journal of Cardiac Failure Vol. 16 No

29. Precipitants of HF Increased metabolic demands
Fever, anemia, infection, tachycardia, hyperthyroidism, pregnancy
Increased circulating volume
Excessive salt or fluid in diet
Renal failure
Increased afterload
Hypertension PE
Impaired contractility
Negative inotropes
Ischemia
Failure to take medications
Progression of underlying disease

30. Inotropes/Vasodilators
ADHF Evaluation and Treatment According to clinical haemodynamic profiles
Dry & Warm
Wet & Warm
PERFUS I ON
Diuretics
± IV Vasodilators
ACEI/BB/Aldost inhib
Dry & Cold
Wet & Cold
The hemodynamic profiles of patients with HF are shown above - good approach guide therapy and inform prognosis for ADHF
The majority (90%) of patients presenting with ADHF are volume overloaded (wet). These patients may have a cardiac index that is unchanged or decreased. Most patients with a decreased cardiac index have SVR, although a minority have unchanged or low SVR.
The signs and symptoms of congestion include orthopnea/PND, jugular venous distention, and peripheral edema.
Signs and symptoms of low perfusion include hypotension, narrow pulse pressure, cool extremities, and decreased mental status.
HR mortality 2.1 for wet and warm and 3.66 for wet and cold vs. dry and warm
↓Vasodilators
↓Diuretics
Diuretics
Inotropes/Vasodilators
↓BP
↑Cr
↑JVP
Crackles
Oedema
CONGESTION
Stevenson et al. Eur J Heart Failure 1999: 1:

31. Therapy Reduce fluid overload Decrease preload and/or afterload
Diuretics
Reduce fluid overload
Vasodilators
Decrease preload and/or afterload
Inotropes
Augment contractility
Mechanical circulatory support
Unresponsive to medical therapy
Little progress

32. Noninvasive Ventilation in Acute Pulmonary Edema
Respiratory Benefits
Hemodynamic Benefits
-alters cardiac transmural presures
-increases tidal volume
-unloads respiratory muscles
-decreases dead space ventilation
-Decreases venous return (preload)
-decreases afterload
-no change or increase in cardiac index
Transmural pressures – difference b/w inside of heart and intrathoracic pressures
-bipap provides pressure support coupled with PEEP to further decrease the work of breathing
-hypothetical advantage of BIPAP not yet demonstrated in clinical trials

33. Intravenous Diuretics
Essential for the management of congestion
Restore volume by increasing excretion of Na and water
Loop diuretics are first line
Diuretic resistance
Dosing
Combination therapy with thiazide
Neurohormonal blockade
Loop diuretics primarily inhibit the sodium-potassium-chloride cotransport system located within the ascending limb of the Loop of Henle. Inhibition of this ion transport system prevents the reabsorption of these ions and a subsequent diuresis occurs
-should never use qd only
-consider thiazides when not effective to block distal reabsorption of sodium/water: distal tubule hypertrophy – with decreased effect of loop diuretics

34. Lasix Administration and Dosing
Bioavailability of oral dosing variable (20-80%)
Gut wall edema, reduced blood flow, protein binding
IV rate preferred in acute HF
Initial dose should be double maintenance or mg IV – titrate to clinical response
Consider continuous infusions if large bolus ineffective
Dose trial: no difference between bolus vs. infusion
Associated with hypotension, renal dysfunction, electrolyte disturbance (K, Mg, Ca), RAAS activation
variable inter/intraindividual oral bioavailability. Therefore IV administration preferred in ADHF
Lasix: peak effect (urine vol and Na excretion) at 1-2 hrs, effect lasts 6 hrs.
May reduce left/right filling pressures within 15mins after administration ie symptomatic imprvt even before diuresis. Due to secretion of prostaglandins inducing venodilatation.
Diuretics have problems
-Intravascular depletion can cause hypotension, diminished CO, reduced GFR and renal dysfunction
– hyponatremia, low K, worse creatinine, activation of RAAS

35. Diuretic Responsiveness
Loop diuretics must reach the lumen of the renal tubule to be effective. Are actively transported from blood to urine by organic acid secretory pumps in the proximal tubules – transport dependent on blood flow to pumps, which is limited in RI, HF, hypotension.
Loop diuretics have a steep S shaped dose-response curve. Frusemide concentration in tubules must reach steep part of curve to achieve natriuresis. Curve flattens ie beyond therapeutic dose, giving increasing doses does nothing.
Renal insufficiency: curve shifts right ie requires higher dose to achieve same fractional Na excretion.
HF: curve shifts to right and down ie higher dose and decreased maximal response: so give higher dose rather than more if no response
Ellison et al. Cardiology 2001; 96:

36. Beneficial effects of volume restoration
Negative sodium and water balance
Decreased cardiac filling pressure
Decreased ventricular dilatation
Improved pulmonary congestion
Decreased ventricular wall stress and endomyocardial ischemia
Decreased functional MR/TR
Improved myocardial function
Improved renal function

37. Vasodilators Reduce filling pressures, afterload: increase CO
Class IIa Recommendation, Level of evidence B
In patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, vasodilators such as intravenous nitroglycerin, nitroprusside, or nesiritide can be beneficial when added to diuretics and/or those who do not respond to diuretics alone
Little data for specific choice: Nitroglycerin vs. Nitroprusside vs. Nesiritide
In normal patients, fairly flat curve with little change in systolic function/CO with increased afterload
Curve progressively steeper with worsening cardiac function – hence vasodilatation/afterload reduction leads to improved CO (not fall in BP)
SBP>90, MAP >65
IV vasodilators for rapid sx relief largely through extensive clinical experience. No RCT to establish best strategy (duration, dose etc)

38. Vasodilator Therapy in Acute HF
Nitroglycerin
Nitroprusside
Stimulates guanylate cyclase
Dose dependent venous and arteriole dilatation
Decreases filling pressures without increasing oxygen demand
Headache
Nitrate tolerance
Equipotent venous and arteriolar dilation
Useful for HTN, valvular dysfunction (AR, MR)
Short half life
Methemoglobinaemia
Cyanide toxicity
Nitroglycerin venodilator, lowers preload and reduces pulmonary congestion.
Most studies of NTG are small and hemodynamic with no sig cv outcome data.
One study has suggested that high dose nitro (3mg isosorbide dinitrate/5 mins) superior to high dose Lasix post MI with HF in reducing need for ventilation. No diff in mortality
Tolerance – due to reflex sympathetic activation, or vascular depletion of sulfhydral groups needed to convert ntg to no
SNP
Release of nitric oxide
Balanced vasodilator that relaxes arterial resistance and venous capacitance vessels. Reduces preload and afterload
Additional SE to GTN: methemoglobinaemia, cyanide toxicity (high dose, renal dysfunction)
Downtitrate slowly to avoid rebound vasoconstriction with abrupt discontinuation

39. Who is the Ideal Candidate for IV vasodilator therapy?
“wet and warm” profile
Patients with acute pulmonary edema/dyspnea and preserved BP (SBP >90)
Acute HF and concurrent cardiac ischemia

40. Vasodilator Dosing Nitroglycerin
Intravenous infusions 5-10 ug/min titrated for desired clinical effect
Oral: isordil mg tid
Transdermal: mg/hr by patch

41. Inotropes – mechanisms of action
Membrane depolarisation causes calcium to enter the cell through L-type channels. Ca acts on ryanodine receptor on SR triggeing a larger release of Ca. Ca binds to troponin C resulting in activation of contractile proteins. The muscle relaxes when calcium is removed into the sarcoplasmic reticulum by SR calcium ATPase pump (Phospholambam inhibits ATPase and SR refill and therefore contraction) or outside the cell by the sodium-calcium exchanger.
In cardiac myocytes, B1 receptor stimulation leads to increased cAMP, which activates Ca channels leading to increased intracellular Ca, which mediates chronotropic response and also increases inotropic response via increased actin-myosin-troponin interaction.
In vascular smooth muscle, B2 receptor stimulation leads to increased cAMP and activation of cAMP-dependent protein kinase, which phosphorylates phospholamban, leading to increased Ca uptake by SR and vasodilation
Phosphodiesterases (PDEs) inhibitors prevent cAMP degradation. Digitalis inhibits Na/K-ATPase. Calcium sensitizers increase the affinity of troponin C for calcium.
Hasenfuss G et al. Eur Heart J 2011; 32:

42. Inotropic Use in Acute HF
Dobutamine
PDE
Milrinone
-all agents increase contractility by increasing levels of cAMP – increased CAMP increase calcium release from the SR and increased contractile force generation by the contractile apparatus
- Either by direct stimulation of adenylate cyclase or dobutamine – increase camp by b mediated stim of adenylate cyclase stimulating c amp prod
- Or inhibiting the breakdown of by PDE 3 inhibition milrinone- selectively inhibits PDE III – that catalyzes the breakdown on cAMP (also vasolilator on SMC and imoroves diastolic fn (lusotropy) by increasing early phase diastolic relaxation
-calcium sensitizers – stabilies troponin molecule in cardiac muscle –prolonging its effect on contractile proteins (also has vasodilating)
-ion channel modulation – vesnarinone
-dobutamine – stim b1 and b3 receptors leads to upregulation of adenyl cyclase and increase ca – has an inotropic more than chronotropic effects, ad low doses indues mily arterial vasodilation and vasoconstriction at high doses
-milrinone produces balanced art and venous dilation
Levosimendan
Adapted from Dorn; Circulation 2004

43. Inotropes and Harm Increased mortality through variety mechanisms
Increase HR
Arrhythmias
Increase myocardial oxygen demand
Direct toxic effect to myocardium: accelerated apoptosis
NOT effective in broad populations of patients with ADHF
Routine use in “wet and warm” detrimental (OPTIME-HF)
Majority of ADHF patients are not in low output state
Increased rates of HF rehospitalisation, mortality with inotropes (ESCAPE, ADHERE)
Stim contractility in hibernating myocardium w/o increasing bf may accelerate apoptosis
OPTIME
No difference in hospitalisation days, death or readmission
Milrinone associated with
Sustained hypotension: SBP <80 for 30 mins requiring intervention MI AF
Higher in-hospital deaths and within 60 days (non-significant

44. Role of Inotropic Therapy
Reserved for those with low output HF
“wet and cold”
Evidence of poor tissue perfusion
Symptomatic hypotension despite adequate filling pressures
Poor response to diuretics with worsening renal function
Unresponsive or intolerant to vasodilators
Short term
Lowest dose
No evidence that one is agent is superior to other “

45. Inotrope Dosing Dobutamine
2-6 ug/kg/min infusions –larger doses needed if profound shock/hypotension
Milrinone
ug/kg/min infusion
Dopamine
2-5 ug/kg/min infusions

46. What about oral HF medications?
Beta blockers
Usually maintained in mild-moderate acute HF
Dose reduced or held when patients felt to have significant reduction in perfusion or need for inotropes
Dose escalation not advised in setting of acute HF
ACE Inhibitors
Dose usually maintained unless significantly hypotensive or acute renal failure
Dose escalation ok once acute symptoms improved (if no worsening renal function)
Digoxin
Dose maintained unless digoxin toxicity

47. Acute HF: Summary
Acute HF results when heart function can no longer meet needs of body
Can be caused by pump failure, or resistance on either side of heart
Key strategy in management is to identify underlying cause
Diuretics are essential
Vasodilators reserved for acute HF with HTN, ischemia or pulmoary edema
Inotropes should only be used in patients with poor perfusion
Novel inotropes have not proved more safe or effective than current care