Heart failure

1. Heart failure Heart failure is the pathological process in which the heart can’t pump enough blood to meet the metabolic requirements of the body due to impaired systolic or/and diastolic function of the heart. Blood returning to the heart faster than the heart can eject it congests the system behind it. Congestive heart failure

2. Classification Right, left, whole Acute, chronic Low-output, high-output Systolic, diastolic Hyperthyroidism Severe anemia VitB1 deficiency Arteriovenous fistula

3. Etiology Underling causes Precipitating factors

4. Underling causes Primary systolic and diastolic dysfunction Excess work demands

5. Primary systolic and diastolic dysfunction Myocardial impairment myocarditis, cardiomyopathy, myocardial angina, myocardial infarction Metabolic abnormalities ischemia, hypoxia, deficiency of VitB1

6. Excess work demands Pressure overload ( postload ) systemic hypertension, pulmonary hypertension, aortic stenosis, pulmonary embolism Volume overload (preload) arteriovenous shunt, thyrotoxicosis, chronic anemia, valvular (mitral, aortic, etc.) regurgitation

7. Precipitating factors pulmonary and systemic infection arrhythmia Pregnancy and delivery water-electrolyte and acid-base disturbance Persistent application of some drugs others

8. Compensation and adaptation Pump reserve Ventricular remodeling Neuro-humoral mechanism Peripheral adaptation Similar to hypoxia

9. Increased preload may be causes by water and sodium retension Increased blood back to heart Decreased stroke volume Pump reserve Frank-Starling mechanism preload↑→ SV ↑ Excessive preload may lead to Venous congestion↑ Myocardial O2 consumption↑ Coronary perfusion ↓ Myocardial contractility ↑ SN ↑ positive inotropic action Myocardial O2 consumption↑ Coronary perfusion ↓ CO↓ Heart rate ↑ SN ↑

10. Ventricular remodeling Myocytes hypertrophy, Myocardial hypertrophy Alteration of myocyte phenotype Nonmyocyte proliferation, extracellular matrix( ECM) remodeling

11. Myocardial hypertrophy Concentric hypertrophy When the primary stimulus for hypertrophy is pressure overload, the increase in wall stress leads to paralell replication of myofibrils, thickening of the individual myocytes, and concentric hypertrophy. Eccentric hypertrophy When the primary stimulus for hypertrophy is volume overload, increased diastolic wall stress leads to replication of myofibrils in series, elongation of the individual myocytes, and concentric hypertrophy.

12. Alterations of phenotype Alteration of protein expression Epigenetic change Gene mutation

13. Nonmyocyte proliferation, extracellular matrix( ECM) remodeling Collagen Ⅲ Collagen Ⅰ Fibroblast Macrophage Endothelia BV SMC

14. Neuro-humoral system ANP HR ↑,Myocardial contractility ↑ Diverting blood to more critical cerebral and coronary circulations positive SN-CA An increase in systemic vascular resistance and the afterload Decreased blood flow to skin, skeletal muscle, kidney, andominal organs. Promoting arrhythmia Increased production of active oxygen species Exhausting myocardial stores of NE and leading to downregulation and a reduction in β-adrenergic receptors negative Ang -Ⅱ vasoconstriction Aldosterone and ADH salt and water retension RAS ↑

15. Pathogenesis Decreased myocardial contractility Diastolic dysfunction

16. Decreased myocardial contractility mechanism • Myocyte loss and structural change • Dysfunction of energy metabolism • Dysfunction of excitation-contraction coupling

17. Myocyte loss and structural change Hypoxia ,ischemia Myocardial fibrosis Toxicity of some humoral factors Necrosis Mitochondria injury Oxidative stress Calcium dyshomeostasis TNF-α Apoptosis

18. Dysfunction of energy metabolism Energy production ↓ Ischemia, hypoxia Mitochondria dysfunction Energy reserve (CP)↓ CPK(B) ↑, CPK(M) ↓ Energy utilization ↓ Activity of myosin ATPase ↓ V1 ↓, V3 ↑

19. Dysfunction of excitation-contraction coupling Reduced Ca 2+ uptake, store and release by SR RyR↓ Reduced influx of extracellular Ca 2+ Dysfunction of Ca2+ binding to troponin

20. Diastolic dysfunction Delayed reposition of Ca2+ ATP deficiency Impaired dissociation of actin-myosin complex Reduced myocardial compliance↓ hypertrophy, fibrosis, etc

21. Clinical manifestations Congestion of pulmonary circulation Congestion of systemic circulation Low cardiac output

22. Congestion of pulmonary circulation Dyspnea exertional dyspnea dyspnea related to an increase in activity. orthopnea shortness of breath that occurs when a person is in supine. paroxysmal nocturnal dyspnea a sudden attack of dyspnea that occurs during sleep and is precipitated by the development of interstitial pulmonary edema. Pulmonary edema

23. Congestion of systemic circulation Systemic venous congestion and hypertension Edema Hepatomegaly and hepatic dysfunction

24. Low cardiac output Fatigue, limb weakness, mental confusion, disturbed behavior, cyanosis, reduced urine, cardiac shock CO 3.5~5.5L/min CI 2.5~3.5L/min.m-2 EF SV/VEDV 0.56~0.78 VEDV ventricular end diastolic volume VEDP ventricular end diastolic pressure PCWP pulmonary capillary wedge pressure 6~12mmHg CVP central venous pressure 4~12cmH2O

25. Principle of treatment General treatment Improving cardiac function isotropic drugs Reducing preload and afterload arterial or venous vasodilators Controlling edema restriction of salt intake, diuretics