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Pathophysiology. Department of Pathophysiology Shanghai Jiao-Tong University School of Medicine. Chapter 13 Cardiac Dysfunction. Content. Introduction Causes and Triggers of Cardiac Dysfunction Classification of Cardiac Dysfunction System Compensation to Cardiac Dysfunction

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Department of Pathophysiology

Shanghai Jiao-Tong University School of Medicine

Chapter 13Cardiac Dysfunction


  • Introduction

  • Causes and Triggers of Cardiac Dysfunction

  • Classification of Cardiac Dysfunction

  • System Compensation to Cardiac Dysfunction

  • Mechanisms and Pathogenesis of Heart Disease

  • Clinical Manifestation and Patho-physiology of Cardiac Dysfunction

  • Pathophysiological basis for the Prevention and Treatment of Cardiac Dysfunction

Vagus Nerve

Synpathatic Nerve


Sinus-Atrial Node

Excitation-Contraction Coupling

Atrial Contraction


Bundle of His

Excitation-Contraction Coupling

Ventricular Contraction



Definition of Heart Failure

  • Loss of cardiac pump activity due to systolic or diastolic dysfunction, leading to insufficient cardiac output and mis-matched tissue perfusion to meet the metabolic demand. The pathogenic process and the resulting syndrome are defined as heart failure.

Congestive Heart Failure (CHF)

CHF represents a late stage of chronic heart failure. Loss of cardiac output and venous return mismatch cause increased plasma sodium level, systemic water retention and increased blood volume, leading to peripheral tissue swelling and cardiac chamber dilation as its main symptoms.

Causes of HF

I. Congenital Heart Disease

1.Defects in Cardiac Myofilament

2.Defects in Cardiac Bioenergenic Metabolism

II. Chronic Cardiac Overload

1.Pressure overload

2.Volume Overload

III. Ventricular Insufficient Filling

Pressure OverloadVolume Overload

Blocking of Aortic Outflow:

Aortic Valve Stenosis Aortic Valve Insufficiency

Left Ventricle Aortic StenosisMitral Insufficiency

Asymmetric Ventricular HypertrophyAneurysm


Pulmonary HypertensionAtrialSeptal Defects

Right Ventricle Pulmonary aneurysmVentricle septal defects

Pulmonary artery stenosisTricupsid InsufficiencyChronic Pulmonary Congestion Pulmonary aortic valve insufficiency

Bi-VentricularHigh Blood viscosity Arteriovenous fistula 、Anemia, Fever, Hyperthyroidism

Increased cardiac load due to enhanced metabolism during fever;

Increased heart rate leading to higher oxygen consumption and reduced coronal perfusion in diastolic phase leading to reduced blood and oxygen


Endotoxin direct injury to cardiomyocytes

Lung infection further reduces oxygen supply to heart

Triggers and Risk Factors

I. Infection

II. Acid/Base Imbalance and feverEletrolyte Metabolism


① H+ binding to Tropon

② Inhibition of SR calcium Release


III. Arrhythmia fever

Loss of atrial/ventricular coordination, insufficeint ventricular filling

and ejection

Reduced diastolic phase, coronary perfusion decrease and myocardial ischemia

Tachycardia increases oxygen consumption and aggravates ischemia

Blood volume overload

IV. Pregnancy

V. Others Physical and emotional stress, infusion too much/too fast, anemia, Digitalis poisoning

Classifications of HF fever

Acute versus chronic heart failure

High-outputversus low-output heart failure

Right-sided versus left-sided heart failure

Contractive versus diastolic heart failure

High output heart failure fever

The cardiac output tends to be elevated in patients with heart failure secondary to hyperthyroidism, anemia, arteriovenous fistulas, beriberi. Due to high metabolic demand, the mismatch remains.

Compensatory mechanism in Heart Failure fever



Contractility 


=CO 


Tissue oxygen and blood supply



Volume Force relation


Contractility 



SV 

Effective Blood Circulation


Blood Volume


RBC, Hemoglobin

ODC right shift



Cardiac Blood Supply

Oxygen Utilization

Heart Rate fever

Quick response, heart rate leading to

increased output within certain limit


Higher HR(>180bpm)increases oxygen consumption

Reduced diastolic phase decreases crononary flow and impairs cardaic perfusion

Pathogenesis of Heart Failure fever

Myocyte depolarization

Cytosolic Ca2+increases from 10-7至10-5mol/L

Excitation contraction coupling

Ca2+binds to TnC,conformational change

TnI removed ,TnT triggers myosin rotation

Expose myosin activity and forming cross-bridge, Ca2+ activates myosin ATPase, hydrolysis of ATP to produce energy

Myosin head rotation, myofilament sliding. Contraction of heart muscle

Key factors to maintain normal systolic and diastolic function

  • Thick/thin myofilament structure

  • Ca2+cycling and homeostasis

  • Energy supply and utilization

I. Systolic Dysfunction function

1. Injured myocyte

2. Metabolic defects

3. EC coupling defects

4. Decompensate remodeling

II. Ventricular Diastolic Defects function

1. Prolonged Calcium Reuptake

2. Cross-bridge Cycling

3. Diastolic Potential

4. Ventricular Compliance reduced

III. Asynchronized Relaxation

Causes and mechanism of HF in late stage hypertrophy function

  • Ischemia/hypoxia due to insufficient coronary supply;

  • Sympathatic stimulation and Catecholamine signaling defects

  • Myosin isoform switch from  to ,ATPase activity is reduced

  • Ion channels, receptors, ion pumps and mitochondrial defects;

  • Interstitial fibrosis and compliance defects

  • Reduced volume vs. surface ratio.

  • Sustained oxygen consumption。

Functional & metabolic alterations in Heart Failure function

  • Heart failure causes organ metabolic changes due to defective cardiac pump. Three major clinical features:

  • Cardiac output reduction

  • Tissue blood supply reducdtion

  • Venous (peripheral and pulmonary) congestion

  • Blood pressure change function

  • Venous hypertension and congestion

  • Increased blood volume and decreased blood flow

Remodeling in Heart function

Reduced Cardiac Reserve

Parameters for Cardiac function:


Parameters for contractility:


Parameters for relaxation and compliance:

–dp/dtmax,T value,ventricular filling volume,ventricular filling rate

Parameters for end-diastolic function:


Pulmonary congestion function

  • Compliance

  • V/Q ratio

  • Cap sensor

  • Bronchial congestion and edema

  • Short of Breath

  • Causes:Congestion, Congestion

  • and Edema

  • symptoms

  • short of breath after labor

  • Sleep apnea

  • orthopnea

  • Pulmonary edema

Pulmonary Edema function

1、Pulmonary capillary pressure

2、pulmonary capillary permeability

Mild heart failure. Symptomatic after physical activity and return to normal after rest

Short of Breath


Severe heart failure, symptomatic at rest and short of beath even laying down. Have to take sitting position

Sleep apnea

LV failure, short of breath in sleep leading to coughing

Short of breath after physical activities return to normal after rest

  • Under physical activity, cardiac return increases, aggravate pulmonary congestion. Pulmonary compliance reduced, leading to higher work load of breathing.

  • increased heart rate, reduced diastolic phase and LV return is shortened, leading to more severe pulmonary congestion.

  • Peripheral ischemia and CO2 retention leading to central stimulation and harder breathing.


Systemic Congestion gravity, reduces cardiac return and alleviate pulmonary congestion and edema.

  • Jugular Veins expansion

  • hepatic expansion, pain, dysfunction

  • Edema

Reduced Cardiac Output gravity, reduces cardiac return and alleviate pulmonary congestion and edema.

  • Aortic Pressure reduction

  • Urine volume reduction

  • Brain function

  • Lethargy and pale

Other organ gravity, reduces cardiac return and alleviate pulmonary congestion and edema. defecdts

  • Liver function defects

  • Abnormal digestive function

Water, electrolyte, Acid/base

  • Water/sodium homeostasis

  • Hpokalemia

  • Hypomagnesemia

  • Metabolic acidosis

Treatment principles of Heart Failure gravity, reduces cardiac return and alleviate pulmonary congestion and edema.

  • Remove causal and triggering factors

  • Improve relaxation

  • Reduce afterload and preload, increase output

  • Adjust humeral regulation

  • Control edema and reduce blood volume

  • Correct homeostasis of water, electrolytes and acid/base.

  • Other, heart transplant

Thank You gravity, reduces cardiac return and alleviate pulmonary congestion and edema.