Introduction for CVS and heart failure

Wesam Radhi Kadhum

Introduction• Heart failure (HF) is a complex,

progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body.

• Its cardinal symptoms are dyspnea, fatigue, and fluid retention.

• HF is due to an impaired ability of the heart to adequately fill with and/or eject blood.

• It is often accompanied by abnormal increases in blood volume and interstitial fluid, hence the term congestive HF �because symptoms include dyspnea from pulmonary congestion in left HF, and peripheral edema in right HF.

• Underlying causes of HF include arteriosclerotic, myocardial infarction, hypertensive, valvular heart disease, dilated cardiomyopathy, and congenital heart disease.

• Left systolic dysfunction secondary to coronary artery disease is the most common cause of HF, accounting for nearly 70 percent of all cases. The number of newly diagnosed patients with HF is increasing, because more individuals now survive acute myocardial infarction.

Role of physiologic compensatory mechanisms in the progression of HF

• Chronic activation of the sympathetic nervous system and the renin-angiotensin-aldosterone axis is associated with remodeling of cardiac tissue, characterized by loss of myocytes, hypertrophy, and fibrosis.

• The geometry of the heart becomes less elliptical and more spherical, interfering with its ability to efficiently function as a pump. This prompts additional neurohumoral activation, creating a vicious cycle that, if left untreated, leads to death.

Renin-Angiotensin System

• HF leads to activation of the renin-angiotensin system

What is the renin-angiotensin system ?

Cardiovascular consequences of heart failure

The renin-angiotensin system is a hormone system that regulates blood pressure and water (fluid) balance.

Angiotensin-converting enzyme inhibitors

• These drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II.

• ACE inhibitors should not be used in pregnant women, because they are fetotoxic.

Adverse effects

• These include postural hypotension, renal insufficiency, hyperkalemia, angioedema, and a persistent dry cough. The potential for symptomatic hypotension with ACE inhibitor therapy requires careful monitoring.

• ACE inhibitors should not be used in pregnant women, because they are fetotoxic.

Angiotensin-receptor blockers

• Angiotensin-receptor blockers (ARBs) are nonpeptide, orally active compounds that are extremely potent competitive antagonists of the angiotensin type 1 receptor.

• ARBs have the advantage of more complete blockade of angiotensin action, because ACE inhibitors inhibit only one enzyme.

• ARBs are a substitute for ACE inhibitors in those patients who cannot tolerate the ACE inhibitors.

Physiology of Muscle Contraction

• The myocardium, like smooth and skeletal muscle, responds to stimulation by depolarization of the membrane, which is followed by shortening of the contractile proteins and ends with relaxation and return to the resting state.

• However, unlike skeletal muscle, which shows graded contractions depending on the number of muscle cells that are stimulated, the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated.

Action potential

• Cardiac muscle cells are electrically excitable. However, unlike the cells of other muscles and nerves, the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized pacemakerm cells located in the sinoatrial and atrioventricular nodes.

• The cardiac cells also have an unusually long action potential, which can be divided into five phases.

Action potential• Cardiac muscle cells are electrically excitable

Cardiac contraction

• The contractile machinery of the myocardial cell is essentially the same as that in striated muscle. The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. Therefore, agents that increase these calcium levels (or that increase the sensitivity of the contractile machinery to calcium) result in an increased force of contraction (inotropic effect).

• The inotropic agents increase the contractility of the heart by directly or indirectly altering the mechanisms that control the concentration of intracellular calcium.

Ion movements during the contraction of cardiac muscle.

ATPase = adenosine triphosphatase

• In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative.

• Membrane potential is the difference in voltage (or electrical potential difference) between the interior and exterior of a cell (Vinterior − Vexterior).

Goals of pharmacologic intervention in HF

The goals are to alleviate symptoms, slow disease progression, and improve survival.

Accordingly, six classes of drugs have been shown to be effective:

1) inhibitors of the renin-angiotensin system, 2) β-adrenoreceptor blockers3) diuretics4) inotropic agents 5) direct vasodilators 6) aldosterone antagonists

Symptoms of heart failure

• Common symptoms of heart failure include breathlessness, tiredness, and swollen feet and ankles. Other symptoms depend on which side of your heart is most affected.

• Left-sided heart failure affects the lungs and ability to breathe. Symptoms include breathlessness when exercising and/or when lying flat, extreme tiredness, wheezing and a cough with a pink froth, usually occurring at night.

• Right-sided heart failure affects the fluid balance in the body. Symptoms include swollen ankles, feeling sick, extreme tiredness and weight gain

The electrical conduction of the heart

• The normal electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node (SA) through both atria and forward to the Atrioventricular Node (AV). Normal/baseline physiology allows further propagation from the AV node to the Ventricle or Purkinje Fibers and respective bundle branches and subdivisions/fascicles. Both the SA and AV nodes stimulate the Myocardium.

1. Sinoatrial node (SA)2. Atrioventricular node (AV)3. Bundle of His4. Left bundle branch5. left posterior fascicle6. left-anterior fascicle7. Left ventricle8. Ventricular septum9. Right ventricle10. Right bundle branch

Anatomy of heart conduction system

• All the wave of electrical activity across the heart muscles can be measured by the electrocardiogram (ECG).

• Function of this conduction system is to keep the heart beating in regular and synchronized manner – thus maintaining cardiac output.

TreatmentDrugs Classification

Theraputics Doses • Digoxin (generic, Lanoxicaps, Lanoxin)

Oral: 0.125, 0.25 mg tablets; 0.05, 0.1, 0.2 mg capsules*; 0.05 mg/mL elixir Parenteral: 0.1, 0.25 mg/mL for injection

• Digitalis Antibody • Digoxin immune fab (ovine) (digibind, digifab)

Parenteral: 38 or 40 mg per vial with 75 mg sorbitol lyophilized powder to reconstitute for IV injection. Each vial will bind approximately 0.5 mg digoxin or digitoxin. Oral: 5, 10, 20, 40 mg tablets.

• Ramipril (Altace) Oral: 1.25, 2.5, 5, 10 mg capsules

• Trandolapril (Mavik) Oral: 1, 2, 5 mg tablets

• Angiotensin Receptor Blockers • Candesartan (Atacand)

Oral: 4, 8, 16, 32 mg tablets • Eprosartan (Teveten)

Oral: 400, 800 mg tablets • Irbesartan (Avapro)

Oral: 75, 150, 300 mg tablets • Losartan (Cozaar)

Oral: 25, 50, 100 mg tablets

• Olmesartan (Benicar) Oral: 5, 20, 40 mg tablets

• Telmisartan (Micardis) Oral: 20, 40, 80 mg tablets

• Valsartan (Diovan) Oral: 40, 80, 160, 320 mg tablets

• Beta-Blockers That Have Reduced Mortality in Heart Failure Bisoprolol (Zebeta, unlabeled use) Oral: 5, 10 mg tablets

• Carvedilol (Coreg) Oral: 3.125, 6.25, 12.5, 25 mg tablets

• Sympathomimetics Most Commonly Used in Congestive Heart Failure • Dobutamine (generic, Dobutrex)

Parenteral: 12.5 mg/mL for IV infusion • Dopamine (generic, Intropin)

Parenteral: 40, 80, 160 mg/mL for IV injection; 80, 160, 320 mg/dL in 5% dextrose for IV infusion

• Angiotensin-Converting Enzyme Inhibitors Labeled for Use in Congestive Heart Failure

• Captopril (generic, Capoten) Oral: 12.5, 25, 50, 100 mg tablets

• Enalapril (Vasotec, Vasotec I.V.) Oral: 2.5, 5, 10, 20 mg tablets Parenteral: 1.25 mg enalaprilat/mL

• Fosinopril (Monopril) Oral: 10, 20, 40 mg tablets

• Lisinopril (Prinivil, Zestril) Oral: 2.5, 5, 10, 20, 40 mg tablets

• Quinapril (Accupril)

• Metoprolol (Lopressor, Toprol XL) Oral: 50, 100 mg tablets; 25, 50, 100, 200 mg extended-release tablets Parenteral: 1 mg/mL for IV injection

• Other Drugs • Inamrinone

Parenteral: 5 mg/mL for IV injection • Milrinone (generic, Primacor)

Parenteral: 1 mg/mL for IV injection; 200 g/mL premixed for IV infusion • Nesiritide (Natrecor)

Parenteral: 1.58 mg powder for IV injection • Bosentan (Tracleer)

Oral: 62.5, 125 mg tablets

END