Acute heart failure

Assoc Prof Serban Balanescu, MD

 Acute heart failure: definition and basic facts

 Rapid development of symptoms and signs of HF requiring urgent medical attention

and hospitalization: abrupt or gradual

 1st reason for hospital admission in pts > 65 yo

 70% of health care expenditure for heart failure

 High mortality rate:

 4-7% in-hospital death

 7-11% 3 months mortality

 25-30% readmission rate at 3 months

 50% have preserved systolic function

 High prevalence of cardiac and extra-cardiac comorbidities

 Epidemiology of AHF: main large scale registries

ADHERE OPTIMIZE-HF EHFS I EHFS II ALARM-HF ATTEND

Study characteristics
Pt number 105388 48612 11327 3580 4953 4862

Region US US Europe Europe International Japan

Time 2001-04 2003-04 2000-01 2004-05 2006-07 2007-11

Pts characteristics
Age, mean (yo) 72 73 71 69.9 66-70 73

Male gender (%) 48 48 53 61 62 58

Known HF (%) 75 87 65 63 64 36
Preserved LVEF (%) 40 51 55 34 25 46.6

Outcomes
In-hospital mortality (%) 4 4 6.9 6.7 11 21
30-90 day mortality (%) 11.2 9 6.6 -- -- --
Readmission rate (%) 22.1 30 24 -- -- --
 Pathophysiology of AHF: 4 key pathogenic
mechanisms

 Salt intake Uncontrolled hypertension

Poor compliance to Hypertensive crisis
treatment Acute pulmonary embolism
Renal dysfunction Volume overload Pressure overload
Acute valve regurge (increased preload) (increased afterload)
Fever

ACUTE HEART FAILURE

Myocardial loss Diastolic dysfunction

(impaired (impaired Tachycardia –
Acute MI
contractility) filling) tachyarrhythmia
Drug toxicity
Hyperthyroidism
Pericardial disease
(tamponade)
Congestion: pulmonary and/or systemic: hallmark of
AHF
 Peripheral:  Mechanisms:
 Weight gain
 Fluid retention
 Jugular vein distension  Low CO: neuro-hormonal activation:
 Liver enlargement aldosterone and ADH excess

 Hepato-jugular reflux  Na+ and water retention

 Ascites, pleural effusion  Fluid redistribution

 Venous and arterial constriction
 Peripheral edema
 Increased pre-load and after-load
 Pulmonary:
 Increased pulmonary capillary pressures
 Dyspnea, orthopnea > 12 mmHg
 Lung rales
 Myocardial injury in AHF

 AHF leads to myocardial ischemia – injury

 In AHF ischemia is due to both  O2 supply and  O2
demand:
 Potentially co-existing CAD
 Low diastolic BP and high intraventricular pressure:  coronary perfusion
 Tachycardia and low diastolic time
 cTn elevation is an independent predictor of outcome in
AHF
 ADHERE Registry: 6% of pts have positive Tn tests
 2.6 x higher in-hospital mortality
 RELAX-AHF: high sensitivity Tn test used
 93% of AHF pts had abnormal Tn tests
 Clinical outcome / natural history in CHF-AHF

Gheorghiade M et al. Am J Cardiol 2005;96 (6A).

 Renal dysfunction in AHF

 Prevalent anomaly in AHF (ADHERE Registry):

 9% of pts: normal eGFR > 90 ml/min
 71% of pts: mild to moderate CKD (eGFR between 30-89 ml/min)
 20% of pts: severe CKD (eGFR < 30 ml/min)
 Vicious circle:
 HF causes kidney dysfunction and this in turn promotes deterioration of heart function
 Heart failure affects renal function in three ways:
 Low CO = low perfusion pressure in the afferent arteriole
 High central venous pressure increases pressure in the efferent arteriole
 Drug therapy, mainly diuretics, reduce intravascular volume and decrease glomerulus
perfusion pressure
 Leads to lower urine output (+ anemia, apoptosis, fibrosis, neuro-hormonal and
inflammatory activation (i.e. TNF)
 Common RF for CKD and HF: diabetes, hypertension, advanced age
 Clinical profile – medical history in pts with AHF

Pts enrolled in the main large scale registries

ADHERE OPTIMIZE-HF EHFS I EHFS II ALARM-HF ATTEND

Pt number 105388 48612 11327 3580 4953 4862

Arterial hypertension (%) 72 71 53 62.5 70 69.4

Coronary disease (%) 57 50 68 53.6 30.7 31.1

Diabetes mellitus (%) 44 42 27 32.8 45.3 33.8

Atrial fibrillation (%) 31 31 43 38.7 24.4 39.6

Renal dysfunction (%) 30 30 17 16.8 21.4 --

COPD (%) 31 28 -- 19.3 24.8 9.5

Anemia (%) -- -- -- 14.7 14.4 --
 Classification of AHF syndromes:
heterogeneous group of patients

 Past history of HF  Congestion and peripheral

 “De novo” AHF perfusion
 Acute decompensated CHF  Warm and dry
 BP on admission”:  Warm and wet
 Hypertensive AHF (>140 mmHg)  Cold and dry
 Normotensive AHF (>85-90 mmHg  Cold and wet
 Hypotensive AHF (<85-90 mmHg)  Clinical profile on presentation:
 LVEF:  Decompensated HF
 AHF with low EF (<40%)  Acute pulmonary edema
 AHF with preserved EF  Cardiogenic shock
 Hypertensive HF
 Right HF
Classification of AHF pts according to the presence of
or absence of congestion

Congestion
No Yes
Hypoperfusion

No

Warm and dry Warm and wet

Yes

Cold and dry Cold and wet

Yancy CW et al. 2013 ACCF/AHA Guideline for the management of HF. Circulation 2013;128:1810-52.
 Acute pulmonary edema: main characteristics

 acute  PCWP ≥ 16-18 mmHg

 Veno-capillary pulmonary HT
= interstitial +/- alveolar stasis
  pulmonary compliance
  respiratory workload and resistance
 Worsening of hypoxemia:
 Hematosis alteration +
  O2 consumption

 “J” receptor activation: cough

 Acute PA with RV volume overload: acute VSD in AMI

Chest X-ray at the onset of acute pulmonary edema
Chest X-ray in advanced acute pulmonary edema
 Outcomes and prognosis: in-hospital and post-
discharge mortality

 AHF: a condition with ominous Heart failure

prognosis Sudden
Acute MI
 In hospital mortality: 4-11% Stroke
13.2
depending on registry Non-CV
 41% of in-hospital deaths due to HF 2.2
alone 2.6
41
 3 months post-discharge mortality:
7-11%
 1 year post-discharge mortality: 26
36%
 Median hospital stay: 6-11 days in
Europe Causes of death in AHF
O’Connor et al. Am Heart J 2010.
 Outcomes in AHF: prognostic indicators

 Clinical and echo:  Medical history

 Age  Recurrent hospitalizations
 Heart rate  Renal dysfunction
 systolic BP  COPD
 6 min walked distance  Anemia
 Need for inotropic agents  Cerebrovascular disease
 Ischemic ECG  Peripheral artery disease
 LVEF  Laboratory
 Restrictive physiology of mitral  BNP, Nt-proBNP
diastolic flow
 cTns
 Creatinine, urea
 Serum Na+
 Hemoglobin
 Liver function tests
In-hospital mortality according to precipitating factors

Overall (%)

Worsen renal function (%)

Pneumonia (%)

Medication non-adherence (%)

Hypertension (%)

Diet non-adherence (%)

Arrhythmia (%)

Ischemia (%)

0 1 2 3 4 5 6 7 8 9

Fonarow et al. Arch Intern Med 2008.

 Treatment of AHF: purpose

 To relieve symptoms; optimize fluid volume status

 To restore respiratory function and gas exchange

 To improve haemodynamics and end-organ perfusion

 To address the underlying cause

 (STEMI, arrhythmia, infection, anemia, deleterious drugs)

 Optimize chronic PO treatment

 (ACEI, beta-blockers, mineralocorticoid receptor antagonists)

 To identify pts that may benefit form non-pharmacologic Rx

 Ultrafiltration, PCI, mechanical circulatory support, CRT, transplant
 Immediate pre-Rx measures

 Close monitoring of O2 saturation, BP, HR, urine output and fluid balance
 Regular blood sampling for acid-base and electrolyte balance (Astrup),
preferably from arterial blood
 Assess frequently creatinine, urea and eGFR and electrolytes, mainly
Na+ and K+
 Classify pts subtypes:
 “wet and cold” and “wet and warm”: highest risk of death
 Urgent mechanical circulatory support

 Identify cardiogenic shock early: treat accordingly

Classes of medication used to treat AHF
 Non-shocked, congested, well perfused pts
(“wet and warm”)
 O2 4-6 l/min per facial mask in hypoxic pts
 Avoid routine use in non-hypoxic pts: may induce vasoconstriction
 Opiates:
 2.5-10 mg morphine IV provide symptomatic improvement
 Anxiolytic, venodilatation
 Nausea, respiratory depression
 Diuretics: IV loop diuretics (furosemide, bumetanide)
 Bolus or infusion
 Peak effect after 1-2h (symptom improvement earlier); subsides at 6h
 Venodilator effect and volume depletion
 Thiazide or thiazide-like drugs to overcome “nephron blockade”
 Low dose dopamine may be added (2.5-5 microg/kg/min)
 Vasopressin receptor antagonists: tolvaptan
 In hypervolemic, hyponatremic pts
 Non-shocked, congested, well perfused pts
(“wet and warm”)
 Vasodilators: BP monitoring is essential
 GTN: venodilator and arteriodilator (high doses)
 Rapid development of tolerance at high IV doses (16-24h)
 Sodium nitroprusside:
 Equally potent systemic veno, arterio and pulmonary artery vasodilator
 0.3 – 0.5 microg/kg/min IV
 May produce coronary steal phenomenon
 Increases cyanide and thiocyanate serum levels in hepatic or renal dysfunction
 Nesiritide: recombinant synthetic analogue of BNP
 Arterio- and venodilator
 Reduces PCWP and systemic BP
 IV infusion 0.01-0.03 microg/kg/min
 Improves symptoms, no mortality benefit
 No impact on renal function, hypotension is common
 AHF therapies recommended by the major current
guidelines

ESC ACC/AHA HFSA

Supplemental O2 1C -- 1C
Opiates 2a C -- --
IV loop diuretics 1B 1B 1B
Vasopressin receptor inh -- 2b B --
Nitroglycerin 2a B 2b A 2b B
Sodium nitroprusside 2b B 2b A 2b B
Nesiritide -- 2b A 2b B
Inotropes in cardiogenic shock 2a C 1C 2b C

Thromboprophylaxis 1A 1B 1B
 Treatment of AHF with cardiogenic shock:
“cold and wet” patients
 Aim:
 increase cardiac output and contractility
 Optimize tissue perfusion and end-organ function
 O2 4-6 l/min per facial mask in hypoxic pts
 Vasodilators: contraindicated
 Inotropic therapy: recommended by all guidelines
 Stabilize and salvage
 Bridge to mechanical circulatory support or transplantation
 None improve survival, some increase mortality
 Classes of medication:
 Sympatho-mymetics (dobutamine, NE)
 Phosphodiesterase (PDE) inhibitors (milrinone, enoximone)
 Calcium sensitizers (levosimendan)
 Increase O2 consumption and risk of arrhythmias
Mechanisms of action of current positive
inotropic drugs
 Inotropic and vasopressor drugs used to treat AHF

Drug Bolus Infusion rate

Dobutamine No 2-20 microg/kg/min

< 3 microg/kg/min (DA1): renal effect

Dopamine No 3-5 microg/kg/min (b1): inotropic effect

> 5 microg/kg/min: (b1, a): vasopressor

Milrinone 25-75 microg/kg in 10-20’ 0.375-0.75 microg/kg/min

Enoximone 0.5-1.0 mg/kg in 5-10’ 5-20 microg/kg/min

Levosimendan 12 microg/kg in 10’ 0.1 microg/kg/min, then 0.05-0.2 microg/kg/min

Norepinephrine No 0.2 – 1.0 microg/kg/min

Epinephrine 1mg, repeated every 3-5 0.05-0.5 microg/kg/min

min during CPR
 Intra-aortic balloon counterpulsation (IABP):
mechanisms of action

LV systole: deflation LV diastole: inflation

Synchronized R wave inflation: 1/1 to 1/3  myocardial workload

 coronary perfusion pressure  cardiac output
 myocardial oxygen consumption  brain and splanchnic blood flow
The Impella device: a different principle for
sustaining LV function in cardiogenic shock

The Impella 2.5, Impella CP,

Impella 5.0, and Impella LD
Catheters, are temporary
ventricular support devices for
short term use (< 4 days Impella
2.5 and Impella CP, and < 6 days
Impella 5.0 and Impella LD)
treatment of cardiogenic shock
that occurs immediately (< 48h)
after acute MI or open heart
surgery with LV failure not
responsive to optimal medical
management.
 Recommended readings

 2016 ESC Guidelines for the diagnosis and treatment of acute

and chronic heart failure. Available online at:
 https://academic.oup.com/eurheartj/article/37/27/2129/1748921/2016
-ESC-Guidelines-for-the-diagnosis-and
 2013 ACCF/AHA Guideline for the Management of Heart Failure.
Available on-line at:
 http://circ.ahajournals.org/content/128/16/e240
 2016 ACC/AHA/HFSA Focused Update on New Pharmacological
Therapy for Heart Failure. Available on-line at:
 http://circ.ahajournals.org/content/134/13/e282