Heart Failure

Department of cardiology,
Sir Run Run Shaw Hospital
Ying Yang
 current situation of heart failure
• Due to the aggravating trend of aging population, the number
of heart failure patients continues to increase.

• Data from developed countries show that: The prevalence of

heart failure was 1.5% - 2.0%.

• In China, the prevalence of heart failure was about 0.9%.

http://www.srrsh.com
 current situation of heart failure
• Heart failure is a serious and end stage of many
cardiovascular diseases. A number of epidemiological
investigations in China show that the number of patients with
systolic or diastolic heart failure is increasing in recent years.
• Although the traditional treatment of severe HFrEF, such as
cardiotonic, diuretic, vasodilator and neuroendocrine
inhibition, has improved the mortality or other heart failure
related events, the 5-year mortality of heart failure is still
around 50%.
• At present, it is still regarded as "the fortress of cardiovascular
field which has not been conquered".

http://www.srrsh.com
 Definition

Heart failure is a complex clinical

syndrome that results from any structural or
functional impairment of ventricular filling or
ejection of blood.
The abnormality of cardiac function fails
to provide adequate blood flow to meet the
metabolic needs of the body's tissues and
organs.
Causes of heart failure

1.Idiopathic

a. Idiopathic dilated cardiomyopathy

b. Idiopathic restrictive cardiomyopathy
C. Idiopathic hypertrophic cardiomyopathy
 Summary of proposed classification system

ARVC, arrhythmogenic right ventricular cardiomyopathy; DCM, dilated cardiomyopathy; HCM,

hypertrophic cardiomyopathy; RCM, restrictive cardiomyopathy

European Heart Journal, Volume 29, Issue 2, 04 October 2007, Pages 270–276, https://doi.org/10.1093/eurheartj/ehm342
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2. Coronary Artery Disease
a. Acute ischemia
b. Left ventricular aneurysm
c. Ischemic cardiomyopathy
3.ventricular overload
a. pressure overload ---- hypertension, aortic
stenosis, pulmonary hypertension, pulmonary valve
stenosis.
b. volume overload ---- mitral regurgitation, aortic
regurgitation, atrial septal defect, ventricular septal
defect, hyperthyroidism, artery-venous fistula.
4. Toxins
a. Ethanol
b. Cocaine
c. Anthracyclines (Doxorubicin/Adriamycin)
5. Metabolic-Endocrine
a. Thiamine deficiency
b. Diabetes
c. Thyrotoxicosis
6. Infiltrative
a. Amyloidosis
b. Hemochromatosis
7. Inflammatory
a. Viral myocarditis
 Forms of heart failure
Heart failure can be described or classified as follows

• 1. Acute and chronic heart failure

• 2. Left, right and biventricular heart failure
• 3. High and low output heart failure
• 4. Diastolic and systolic dysfunction
• 5. Asymptomatic and congestive heart failure
Acute heart failure
Refers to the situation in which an individual who is
completely asymptomatic before the onset of heart failure
symptoms decompensates when there is an acute injury to the
heart, such as myocardial infarction or rupture of a heart
valve.

Chronic heart failure

Refers to an individual whose symptoms have developed
over a long period of time, often when there is preexisting
cardiac disease.
Left-sided failure

An abnormal cardiac condition characterized by the

impairment of the left side of the heart and elevated pressure
and congestion in the pulmonary veins and capillaries.

Right-sided failure

An abnormal cardiac condition characterized by the

impairment of the right side of the heart and congestion and
elevated pressure in the systemic veins and capillaries.
Low output heart failure:

Characterized by insufficient forward output both at

rest and during times of increased metabolic demand.

High output heart failure:

Occurs with severe anemia or thyrotoxicosis, results when

the heart is unable to meet the abnormally elevated
metabolic demands of the peripheral tissues.
Systolic heart failure:
The inability of the heart to contract strongly enough to
provide adequate blood flow to the periphery.
– “weak heart”
– LVEF < 55%

Diastolic heart failure:

Occurs when there is abnormal relaxation of the
myocardium, resulting in reduced filling of the ventricle.
– “stiff heart”
– Normal LVEF
 Pathophysiology

• 1. Frank-Starling’s Law of the heart

The more a myocyte or ventricular chamber is
stretched, the more it will contract.

cardiac contractility
Lengeth of sarcomere 2-2.2um
• 1. Frank-Starling’s Law of the heart
a. Cardiac output can be augmented by
increasing the stroke volume or heart rate.
b. Stroke volume is dependent on the
contractile state of the myocardium, left
ventricular filling (preload), and resistance
to left ventricular emptying (afterload).
1. Frank-Starling’s Law of the heart
• 2. Activation of neurohormonal systems in
Heart Failure

a. Renin-angiotensin-aldosterone system helps maintain

cardiac output and tissue perfusion by stimulating arterial
vasoconstriction through production of angiotensin II and
expansion of intravascular volume by retaining sodium and
water.

b. Sympathetic nervous system helps maintain tissue

perfusion by increasing arterial tone, as well as increasing
heart rate and ventricular contractility.
• RAAS in Heart Failure
• 2. Activation of neurohormonal systems in
Heart Failure

Activation of these systems is associated with several

deleterious effects, including

• Elevation in ventricular filling pressures, which may result in

pulmonary and/or systemic edema
• Depression of cardiac function secondary to an increase in
peripheral vascular resistance
• Stimulation of myocardial hypertrophy and left ventricular
remodeling
• 3. Myocardium impairment and remodeling
• sympathetic nervous
system
initial myocardium impaired • RAAS
ventricular overload • endothelins
myocardium infarction • TNF-α, IL-6
inflammation • mechanical stress
• oxidative stress

• overstretching of
disease progress chamber enlargement the myocytes
heart failure myocardial hypertrophy • further elevation in
complication embryo gene phenotype wall stress
death extracellular matrix change • increase in myocyte
death
• ventricular dilation
• 4. Diastolic heart failure
“filling problem”

↓ ventricular compliance (hypertrophy, ischemia, arrhythmia) →

↑ LVEDP → ↓ ventricular filling → ↓ stroke volume
 normal
pressure

compliance
↓
compliance
↑

Volume
Ventricular pressure-volume curve switch to left and
upward during diastolic dysfunction.
Clinical Features

• pulmonary congestion
• systemic venous congestion
• tissue perfusion deficiency due to
low cardiac output.
§1 Chronic heart failure
clinical manifestation

1. left ventricular heart failure

Mainly manifested with pulmonary congestion and reduction

of cardiac output
A. symptom

1. dyspnea

1) shortness of breath
2) paroxysmal nocturnal dyspnea: often with
wheezing rale of both lung cardiogenic asthma
3) Orthopnea: venous return increased by the recumbent
position pulmonary venous and capillary pressure
increase interstitial pulmonary edema
pulmonary compliance decrease respiratory
resistance elevate
4) acute pulmonary edema
2. cough and hemoptysis
pink-tinged frothy sputum

3. fatigue on exertion

4. urinary system symptom

at early stage, nocturia
at advanced stage, oliguria
B. Sign
1. general sign
increased heart rate, pulse pressure may be
narrowed, SBP decrease, cyanosis, cold.
2. Heart sign
 diffuse and left lateral displaced apical impulse
 gallop during early diastolic period, accentuated P2,
systolic murmur at cardiac apex
 pulsus alternans occurs when left ventricular ejective
impedance increase

3. Lung sign
crackles on auscultation of the lung fields
About 25% CHF patients develop pleural fluid which may
cause decreased breath sounds
2. Right ventricular Failure
Congestion of systemic circulation

A. Symptom
1) gastrointestinal tract
anorexia, distention, nausea, vomiting, constipation
2) kidney
kidney congestion, renal dysfunction
3) hepatic region pain: congestion, hepatic cirrhosis
B. Sign
1. heart sign
• right ventricular dilation
• strong impulse during the systolic period at the left sternal
border, xiphoideusal pulsation
• diastolic gallop
• relative tricupid incompetence
2. distended neck veins, hepatojugular reflux
3. liver congestion and tenderness occur before edema
Acute: jaundice
Chronic: hepatic cirrhosis
4. edema

Occur after engorgement of the neck veins and liver

enlargement, which is typical sign of right heart failure. Usually
involves the lower extremities. In patients with severe, long-
standing heart failure, the edema can involve the thighs and
abdomen and ascites may develop.
At early stage, edema occurs in the morning, worsens during
the day and decreases overnight.
If complicated with malnutrition or hepatic dysfunction, face
edema occurs, and prognosis is poor.

5. pleural fluid, ascites, pericardial effusion

 3. Biventricular heart failure

Displayed with clinical manifestations of

both left and right heart failure.
 4. Diastolic heart failure

Conditions with normal systolic function and

decreased diastolic function mainly include:

(1) Systemic arterial hypertension

(2) Severe aortic stenosis
(3) Acute ischemia
(4) Hypertrophic cardiomyopathy
(5) Infiltrative cardiomyopathy (e.g., amyloid)
 Diastolic heart failure

• Symptoms and signs may be similar with

systolic dysfunction
• The most common symptom associated with
diastolic dysfunction is dyspnea on exertion
• In some patients, symptoms may be abrupt in
onset and are associated with acute pulmonary
edema
 Investigation

1. routine laboratory examination

blood, urine, electrolyte, renal function, liver function

2. ECG
a. not specific
b. Abnormalities may provide etiological clues
• prior myocardial infarction
• left ventricular hypertrophy
• significant arrhythmias
c. V1ptf<-0.03mm/s left atrial overload
3. Echocardiography: evaluating the severity of
chamber enlargement, ejection fraction, and wall
motion abnormality.
a. EF (ejection fraction)
• normal --- >55%
• decrease in the pumping strength of the heart --- < 50%
• significant decrease --- < 30 to 35%
b. LVEDd
• male 45 to 55mm
• Female 35 to 50mm
normal Dilated
cardiomyopathy
4. Chest X ray
a. evaluation of chamber enlargement
cardiothoracic ratio > 0.5

b. pulmonary venous congestion

venous blood redistribution to the upper lobes

C. interstitial edema
Kerley B lines: reflect chronic elevation of left atrial pressure and
represent chronic thickening of the interlobular septa from edema.

d. alveolar edema
perihilar infiltration or peripheral patchy infiltration
X-ray
Vascular redistribution
Interstitial edema
Alveolar edema
 BNP – the WBC of CHF?

• B-type Natriuretic Peptide

• BNP released in response to ventricular stretch
• Causes natriuresis, vasodilation and inhibition
of renin–angiotensin system
 BNP in CHF

1038±163
1200

1000
BNP
800
(pg/mL)
600

400

200 63±16
0
No CHF CHF
N=44 N=44
Cause of edema
Adapted from Maisel, Cardiol. Clinics; 19(4),2001
 CHF vs. COPD
1076±136

1200

1000

BNP 800

(pg/mL) 600

400
86±39
200

0
COPD CHF
N=56 N=94
Cause of Dyspnea

Adapted from Maisel, Cardiol Clinics; 19(4),2001

BNP in diagnosis of CHF

Adapted from Maisel et al NEJM, 347(3); 2002

• 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of
Heart Failure
Diagnosis and differential diagnosis

Clinical diagnosis include:

etiology
--- underlying disease and provocation factor
pathoanatomy
pathophysiology
heart rhythm
cardiac function
NYHA classification Annual Mortality
Ⅰ no activity limit, daily activity don't lead to symptom. 5%

Ⅱ slight activity limit, no symptom at rest, daily activity 5-10%

(2 blocks or 2 flights of stairs) lead to symptom.

Ⅲ obvious activity limit, no symptom at rest, daily activity 10-20%

lead to symptom.

Ⅳ have symptom at rest. 20-50%

 Forrester classification

CI PCWP
type Clinical manifestation
(L/min·m2) （mmHg）

≥2.2 ≤18（2.4） No peripheral perfusion deficiency and

Ⅰ pulmonary congestion, no symptom and sign
of heart failure
≥2.2 ＞18（2.4） No peripheral perfusion deficiency, pulmonary
Ⅱ congestion ,no obvious clinical manifestation

＜2.2 ≤18（2.4） peripheral perfusion deficiency, no pulmonary

Ⅲ congestion ,seen in right ventricular infarction
and blood volume deficiency
＜2.2 ＞18（2.4） peripheral perfusion deficiency and
Ⅳ pulmonary congestion ,severe type
 Killip classification
(applicable for AMI patients)

I. no obvious heart failure symptom, no moist rales,

PCWP may elevate
II. slight to moderate heart failure, moist rales < 50% lung
field
III. severe heart failure, moist rales >50% lung field, acute lung
edema
IV. cardiogenic shock, BP<90mmHg, oliguria <20ml/h, skin cold,
cyanosis, tachypnea, rapid pulse
V. cardiogenic shock and pulmonary edema
Differential diagnosis

1. Left heart failure

Pulmonary disease, ARDS
2. Right heart failure
constrictive pericarditis
renal edema
hepatic cirrhosis
Management of heart failure

Etiologic treatment
Pathophysiological basis for treatment

Improvement of myocardial
contraction and relaxation

Reduce cardiac preload

and afterload

increase cardiac output

Control edema
General therapy
1. Etiologic treatment
underlying disease, provocation factor.

2. Reduction of ventricular overload

a. rest and sedative agent
b. salt-intake control
normal adult intake 3-6g sodium per day
Ⅰ0 heart failure : 2g sodium per day
Ⅱ0 heart failure : 1g sodium per day
Ⅲ0 heart failure : 0.4g sodium per day
c.water intake control
for not severe patient, intake of water 1.5-2.0L per day is
appropriate.
in severe heart failure, water retention, serum albumin
decrease, diluted hyponatremia, control of water intake is
recommended
 Drug therapy
• ACE-inhibitors / ARBs
• ARNI
• Aldosterone antagonist
• vericiguat
• β-Blockers
• SGLT2 inhibitors
• Diuretics
• Vasodilators
• Inotropic agents
ACEI / ARB
 ACEI / ARB

• Rationale: ↓ afterload, ↓remodelling, antiproliferative

Recommendations:
– All patients with LVEF <40% or Class II – IV CHF should
be on ACEI
– Use ARB if ACEI is not tolerated
 Angiotensin receptor -neprilysin inhibitor (ARNI)’s
central role in the inhibition of RAAS and NEP
Myocardial injury/overload

HFrEF

↑SNS ↑RAAS ↑NPS (natriuretic peptide

system)/ Ventricular wall stress
β-blockers ↑renin ↑ANP/BNP

angiotensinogen NEP
ACE ↑Ang I ↑NPRA
NEPi
Bradykinin
ACE
degradation
↑Ang II ARNI (sacubitril/valsartan) ↑GC-A

AT1R ARB ↑cGMP

vasoconstricition aldosterone ↑PKG

Hyperplasia
↑ROS MRCA
fibrosis
sodium Vasodilation
natriuresis
retention ↓fibrosis
yellow arrow means activation; grey arrow means block
1. Braunwald E.J Am Coll Cardiol. 2015 ;65(10):1029-41.
NO–SGC–CGMP PATHWAY IS INVOLVED IN THE REGULATION OF IMPORTANT
PHYSIOLOGICAL MECHANISMS OF CARDIOMYOCYTES
The generation of second messenger molecule - cyclic guanosine monophosphate (cGMP)
is through activation of sGC by nitric oxide (NO) and activation of pGC by NPs
Natriuretic Neprilysin inhibitor in
Extracellular NO peptide ARNI increases the level
of neprilysin (NPs) which
excerts the beneficial
effects on caridiovascular
cGMP and renal system

Cardiac
myocyte
sGC pGC
Intracellular PKG

The target effect of PKG phosphorylation

Sarcoplasmic Hypertrophic
Myocardial Myofilament Calcium Reperfusion
reticulum calcium signal
stiffness ↓ sensitivity ↓ influx ↓ injury ↓
reuptake ↑ expression ↓

cGMP=cyclic guanosine monophosphate; HF=heart failure; pGC=particulate guanylate cyclase; PKG=protein kinase G; sGC=soluble guanylate cyclase; SR=sarcoplasmic reticulum;
VSMC=vascular smooth muscle cells; NO=nitric oxide.
1. Gheorghiade M et al, Heart Fail Rev. 2013;18:123. 2. Mann DL et al, Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Elsevier/Saunders; 2015. 3. Boerrigter G
et al, Handb Exp Pharmacol. 2009:485. 4. Breitenstein S et al. Handb Exp Pharmacol. 2017;243:225. 5. Felker G, Mann D. Heart Failure: A Companion to Braunwald’s Heart
Disease. Elsevier; 2020; 6. Armstrong PW et al. JACC Heart Fail. 2018;6:96; 7. Tsai E et al. Pharmacol Ther. 2009;122:216; 8. Sandner P. Biol Chem. 2018;399:679.
68
 pharmacological effect of Vericiguat

The new
soluble guanylate cyclase (sGC)
stimulant directly stimulats NO
receptor sGC by two modes.
•By stabilizing the binding of NO
with sGC, it makes sGC more
sensitive to endogenous NO；
•Also it can stimulats sGC
directly by different binding sites
independent of NO.
 VERICIGUAT INCREASES sGC ACTIVITY TO IMPROVE
MYOCARDIAL AND VASCULAR FUNCTION
Oxidative stress Decreased NO Endothelial dysfunction
Decreased sGC activity
Low NO availability

Extracellular

Vericiguat

cGMP

Intracellular
Increased
sCG cGMP production
Increases
sGC activity

Heart
Vasculature

↓ Progressive myocardial stiffening

↓ Myocardial thickening ↓ Arterial constriction
↓ Ventricular remodeling ↓ Vascular stiffness
↓ Fibrosis

cGMP=cyclic guanosine monophosphate; HF=heart failure; NO=nitric oxide; sGC=soluble guanylate cyclase.
4
Heart Fail Rev. 2013;18:123-34.; Braunwald’s Heart Disease 2015; Handb Exp Pharmacol. 2009;191:485-506; Handb Exp Pharmacol. 2017;243:225-47; Heart Failure: A Companion to Braunwald’s Heart Disease 2020. 4
 β-blockers

• Rationale: ↓ central sympathetic tone, decreases

cardiotoxic effect of catecholamines

Recommendations:
– All stable class II, III, IV CHF unless contraindication or
inability to tolerate
– In acute heart failure, avoid or ↓ dose if already on
β-blocker
 Aldosterone antagonist

• Rationale: inhibit the deleterious effect of

aldosterone on heart
• Spironolactone, Eplerenone

Recommendations:
– Applicable for patients with moderate to severe HF,
Class III – IV CHF, LVEF<40%, HF after MI
In normal renal glucose handling, 90% of glucose is reabsorbed
by sodium-glucose co-transporter 2 (SGLT-2)

Majority of
glucose is
reabsorbed by
SGLT2 (90%)

Proximal tubule

Remaining
SGLT2 glucose is
Glucose reabsorbed
Glucose filtration by SGLT1
(10%) Minimal
to
no glucose
excretion

Adapted from: 1. Wright EM. Am J Physiol Renal Physiol 2001;280:F10–18; 2. Lee YJ, et al. Kidney
Int Suppl 2007;106:S27–35; 3. Hummel CS, et al. Am J Physiol Cell Physiol
2011;300:C14–21; 4. Marsenic O. Am J Kidney Dis 2009;53:875–83.
 Key Physiological Effects of SGLT-2 Inhibition

↑NATRIURESIS
↑GLYCOSURIA
↑OSMOTIC DIURESIS

↓HbA1c ↓Plasma volume

↓Interstitial fluid

Glyce Extra-
↓Glucotoxicity mic Glyce
↓Insulin resistance mic ↓Blood pressure
↑β-cell function Effect
s of Effect
SGLT- s of
2i SGLT-
2i ↓Glomerular
↓Body weight
hyperfiltration

Metabolic,
Cardiovascular, and
Renal Improvements
HbA1C=hemoglobin A1C; SGLT-2=sodium-glucose co-transporter 2; SGLT-2i=sodium-glucose co-transporter 2 inhibitor.
1. Heerspink HJL, et al. Kidney Int. 2018;94(1):26-39. 2. van Baar MJB, et al. Diabetes Care. 2018;41(8):1543-1556. 3. Tamargo J. Eur Cardiol. 2019;14(1):23-32.
 SGLT2 inhibitors

Recommendations:
– In patients with symptomatic chronic HFrEF, SGLT2i are recommended
to reduce hospitalization for HF and cardiovascular mortality,
irrespective of the presence of type 2 diabetes
– In patients with HFmrEF, SGLT2i can be beneficial in
decreasing HF hospitalizations and cardiovascular mortality
– In patients with HFpEF, SGLT2i can be beneficial in
decreasing HF hospitalizations and cardiovascular mortality
 Diuretics

• Rationale: prevent fluid retention, decrease preload

– Many RCTs – none has shown long term morbidity and
mortality benefit
– Major role is symptom control

Recommendations:
– Use for symptom control: mild – hydrochlorothiazide
(HCTZ), moderate – loop diuretics, severe - loop diuretic
+ spironolactone
– Pay attention to water and electrolyte disturbance
 Diuretics recommended by heart failure guidelines
Maximum Routine daily
drug Initial dose
daily dose dose
Loop diuretics
Furosemide 20~40mg, 1 /d 120~160mg 20~80mg
Bumetani 0.5~1.0mg, 1次/d 6~8mg 1~4mg
Torasemide 10mg, 1 /d 100mg 10~40mg
Thiazide diuretics
Hydrochlorothi 12.5~25.0mg, 1~2 /d 100mg 25~50mg
azide
Metolazone 2.5mg, 1 /d 20mg 2.5~10.0mg
Indapamide 2.5mg, 1 /d 5mg 2.5~5.0mg
Potassium preserving diuretics
amiloride 2.5~5.0mg, 1 /d 20mg 5~20mg
Triamterene 25~50mg, 1 /d 200mg 100~200mg
New diuretics
Tovaptan 7.5~15.0mg, 1 次/d 30mg 15mg
Chinese guidelines for diagnosis and treatment of heart failure, 2018
 Tolvaptan
Thiazide

URINE
V2R V
AQP2
Acetazolamide MRA

Loop H2O
Mannitol diuretics

AQP2 V2R Tol

H2O
Collecting Collecting Inner
duct duct cell vessel
Mannitol

• Cause diuresis
• Increase free water clearance
• Elevate serum sodium
 Vasodilators

• Rationale: decrease preload and afterload

– Nitrates: improve coronary flow
– CCBs: amlodipine/felodipine decrease afterload
– No data showing additional benefits if patient is already on ACEI
and β-blocker

Recommendations:
– Consider to use if patient is intolerant to other agents
– May be used to control hypertension, angina in patients
with CHF
Recombinant human natriuretic peptide
 Inotropic agent-digoxin

• Rationale: increases myocardial contractility,

symptomatic relief, rate control

Recommendations:
add to regimen if patients remain symptomatic
despite ACEI and β-blocker
 Other inotropic agent

1. β-adrenocepter agonists
Dopamine
2-5ug/Kg·min activate dopamine receptor,
increase renal flow
6-10ug/Kg·min activate β-receptor,
increase myocardial contractility
>10ug/Kg·min activate α-receptor,
vasoconstriction
Dobutamine
2-7.5ug/Kg·min
2. Phosphodiesterase inhibitor

Inhibit cAMP degrade increase intracellular

cAMP Ca2+ increase cardiac contraction
increase
Amrinone Milrinone
 levosimendan --calcium sensitizer

levosimendan

Troponin C

levosimendan
Troponin C
levosimendan -- ATP sensitive potassium channel opener
 Treatment for Diastolic Dysfunction

• Ischemia control (nitrates)

• Rate control (β-blockers, CCBs)
• Hypertension control (ACEI, CCBs)
• Caution: Aggressive diuresis and venodilation
may worsen situation
Refractory heart failure
1) Have the etiology and precipitating
causes been established?
2) Are drug dose optimal?
3) Is the patient adhering to an adequate
low-salt diet?
4) Need cardiac transplantation?
Initial assessment of acute heart failure—CHAMP
 2016 ESC Guidelines for the diagnosis and treatment of acute
heart failure
• C Acute coronary syndrome：Interventional strategy for
revascularization is recommended
• H Hypertension emergency： Rapid reduction of blood
pressure should be the main target of treatment
• A Arrhythmia ：Cardioversion, drugs and pacing therapy
• M Acute mechanical cause： e.g. ACS (rupture of free wall,
perforation of ventricular septum, acute mitral
regurgitation), mechanical complications of chest
trauma or cardiac intervention, or acute valve
insufficiency secondary to infective endocarditis ,
dissection, thrombosis or other causes (cardiac tumor,
etc.). Usually requires surgery or percutaneous
interventional circulatory support.
• P Acute pulmonary embolism ： When shock or
hypotension develops, thrombolysis, catheterization or
surgical thrombectomy are recommended.
• Others: control infection, control blood sugar level,
correct anemia
European Heart Journal Advance Access published May 20, 2016
Acute pulmonary edema
Emergency treatment
1) Position: Don't keep patient in a supine position

2) Maintain oxygenation: high concentrations of O2 should be

given by mask or with continuous positive airway pressure （CPAP）
/ Bi-level Positive Airway Pressure （BiPAP）
3) Morphine sulfate 3-5mg IV or 5- 10mg IM can reduce agitation,
induce transient arterial and venous dilation, reduce arterial
resistence, decrease respiratory rate, slow heart rate, and reduce
respiratory and cardiac burden
4) Intravenous administration of a fast-acting diuretic, (e.g.
furosemide 40mg IV) can initiate diuresis in 15 to 20 min.
5) Alternating tourniquets are effective with BP cuff applied to
2 limbs, inflated at pressure between diastolic and systolic
pressure, deflated and alternated 10 to 20 min.
6) Vasodilator drugs
7) Digitalis
8) Aminophylline
9) others
 Non-drug therapy for heart failure

• Ultrafiltration
• ICD
• CRT
• His-Purkinje system pacing
• LVAD
• Cardiac transplantation
 Ultrafiltration

• The hospitalization of 90% of ADHF is due to volume

overload, a consequence of excess fluid from both internal and
exteral blood vessel.
• In recent years, a great advance has been obtained in
ultrafiltration equipment and technology, especially the special
equipment for heart failure ultrafiltration, which provides
effective treatment and more choices for the management of
volume overload.
 Working
principle

Ultrafiltration pressure

Filter
Blood leak Pre-filter pressure
detection

venous pressure
Ultrafiltration pump
Blood pump

Air detection

median cubital vein Arterial pressure

median
Vein clip
Weight sensor cubital vein

Ultrafiltrate
 All Enrolled Discharges in Over 12 Months (01.01.2003–12.31.2003)

50 Diuretics are not

valid 50%
40
Enrolled Discharges (%)

30%
30 24%

20 15%
13%
7% 6%
10 3% 2%
0
(<-20) (-20 to -15) (-15 to -10) (-10 to -5) (-5 to 0) (0 to 5) (5 to 10) (>10)

Change in Weight (lb)

Change in Weight From Admission to Discharge

ADHERE Registry. 2003 National Benchmark Report. http://www.adhereregistry.com

Diuretics are not valid

 meq/L Ali SS et al. Congest Heart Fail.

160 Na 2009; 15:1-4

140 134

120
IVD
100 UF
80
60 K
60
41
40 Mg
20 3.7 5.2 2.9
0

The sodium removal of diuretic is only half as

much as ultrafiltration
Comparison of cycle paths
 Heart failure ultrafiltration

Indications Cotraindications

1、Heart failure with fluid 1、BP≤90mmHg and poor circulation

overload in extremities
2、Severe mitral valve or aortic
stenosis
2、The diuretic resistance
3、Contraindication for heparin
4、Needing for dialysis
3、Needing for hospitalization
because of volume overload 5、Acute right ventricular infarction
6、Systemic infection
 Security
Low blood volume and pressure
With traditional treatment, the blood presure reduction is in 20% of the
patients, but it is rare to see in the ultrafiltration (UF) unit. The amount of
blood plasma is decided by the shifting balance between the UF speed and
Plasma Refill Rate (PRR), Theoretically, the low blood volume will not
occur if UF speed does not surpass PRR.
In UNLOAD, with 500ml/h in UF, there was no difference in the
incidence of hypotension between the UF and the control group.
Hypotention is rare in UF treatment of heart failure with UF speed lower
than PRR.
 Security

Impacts on kidney function

In UNLOAD trial, no difference exists concerns kidney function between the
UF and the control group, and the changes in Scr has no significant meaning after
treatment. What is more, the senstivity of diuritics recovers after UF treatment in
some patients. Ultrafiltration may even have been benificial to kidney function.
 Security

The balance of electrolyte and acid-base

The crystal osmotic pressure of UF fluid is equal to blood plasma. The UF
treatment does not affect the concentration of electrolyte and acid-base balance.
So there is no need to detect electrolyte and acid-base balance during UF
treatment.
ICD
 ICD
• ICD therapy should be considered only after guideline directed medical
therapy (GDMT) has been optimized for 3 to 6 months in patients with
expected survival of more than 1 year with good functional status.

• Primary prevention:
• Patients with HFrEF with an LVEF 35% with NYHA class II or III HF
symptoms despite GDMT in nonischemic cardiomyopathy and ischemic
cardiomyopathy at least 40 days after MI
• Patients with HFrEF secondary to ischemic cardiomyopathy with an
LVEF of 30% despite GDMT who are NYHA class I and at least 40 days
post MI
 ICD
• Secondary prevention:
• Patients who have survived a prior cardiac arrest or sustained ventricular
tachycardia (VT) after reversible causes have been excluded
• Patients with conditions associated with a high sudden death risk who
experience unexplained syncope with or without evidence of sustained VT
or ventricular fibrillation at electrophysiological study
CRT or CRTD
 CRT or CRTD
• Patients with HFrEF with an LVEF of 35% or less in sinus rhythm with an
LBBB and a QRS duration of 150 ms or greater with NYHA class II to IV HF
symptoms on GDMT.
• CRT may be useful in patients with HFrEF in sinus rhythm with either a non-
LBBB pattern and QRS of 150 ms or greater, an LBBB QRS duration of 120
to 149 ms, or if the underlying rhythm is atrial fibrillation and atrioventricular
junctional ablation or pharmacologic rate control will achieve 100%
ventricular pacing with CRT
• CRT also can be considered in those with LVEF 35% undergoing a device
implantation with a high anticipated requirement of right ventricular pacing
(>40%), or those patients with NYHA class I symptoms more than 40 days
after MI with an LVEF of 30% in sinus rhythm with LBBB QRS 150 ms.
 Development of physiological pacing

VVI→VVIR Search AV、MVP BiV pacing

Exercise increases Reduce ventricular Biventricular synchronous
heart rate pacing pacing

VVIR→DDDR RV septal pacing HBP/LBBP

Atrioventricular Right ventricular His-Purkinje conduction
sequential pacing septal pacing system pacing (HPP)

• Advantages of HPP: protect and improve cardiac function, avoid right ventricular pacing

• Patients with high percentage of RV pacing (VP > 40%) benefit more, and could avoid
deterioration of cardiac function
 His-Purkinje conduction
system and Electrical conduction of the heart
Normal cardiac activation The location of his bundle
and Electrical conduction
• His bundle originates
from the atrioventricular
node, which is located
above the interventricular
septum and connected
with the left and right
bundle branches. It can
be distinguished from
the atrioventricular node
by electrophysiological
examination
• Electrical signal is
transmitted to ventricle
through his bundle-left
and right bundle branch-
Purkinje fiber, which
causes myocardium
contraction
• The conduction speed of
electrical signal through
bundle branch system is
much faster than
myocytes.
Alanis J, Lopez E, Pulido J. The H Potential and the Conduction Velocity of the Bundle of His. J.
Physiol. 1959: 147: 315-324
 His-Purkinje conduction system pacing
• Including his bundle pacing (HBP) and left bundle branch regional pacing
(LBBP)
• By capturing the bundle branch conduction system, excitation and
synchronization by physiological high-speed electrical conduction can be
achevied
LBBB Left
ventricle his bundle
pacing HBP left bundle
branch
AVN
regional
Left atrum Left anterior
pacing起搏
Branch
His Proximal
LBBP
AVB AVB Left posterior His distal
1 2 Branch Trunk of left
His bundle branch LV
Bundle Right Bundle septum
Branch

RV
Right atrum

Right
ventricle
Pacing site
Indications of His-Purkinje conduction system pacing therapy

• Atrioventricular node block：II°和III° AVB

Brady • Subnodal block, AVB in his bundle
indication • Atrial fibrillation with slow ventricular rate
• Atrial fibrillation with fast ventricular rate and ventricular
rate can not be controlled by drugs (EF < 40-50%)

CRT • Patients with indication of CRT failed in left ventricular

electrode implantation
indication
• non-responders of CRT
VAD
• Impella
extracorporeal membrane oxygenation
（ECMO）
 Cardiac transplantation
• First successful cardiac transplantation in 1967
• Advances in immunosuppressive therapy have led to improved long-
term survival of transplant recipients, with 1-year, 3-year, and 5-year
posttransplant survival rates of 87.8%, 78.5%, and 71.7% in adults,
respectively, and a median survival of 10.7 years
 Content

1. general concept
1) Causes of heart failure
2) Pathophysiology

2. chronic and acute heart failure

1) Clinical manifestation
2) Laboratory examinations
3) Diagnosis and differential diagnosis
4) Treatement
 Reference

 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic
heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi:
10.1093/eurheartj/ehab368.
 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A
Report of the American College of Cardiology/American Heart Association
Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022
May 3;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012. Epub 2022 Apr 1.
 中 国 心 力 衰 竭 诊 断 和 治 疗 指 南 2018 （ 2018 Chinese Guidelines for
the Diagnosis and Treatment of Heart Failure ），中华医学会心血管病学
分会心力衰竭学组, 等. 中华心血管病杂志. 2018,46(10): 760-789