Heart Failure

CO = SV x HR-becomes insufficient to meet metabolic needs of body SV- determined by preload, afterload and myocardial contractility Classifications HF

Systolic failure- dec. contractility Diastolic failure- dec. filling Mixed

90/140= 64% EF- 55-65 (75) normal

Factors effecting heart pump effectiveness

Volume of blood in ventricles at end diastole Depends on venous return Depends on compliance

Afterload Force needed to eject blood into circulation Arterial B/P, pulmonary artery pressure Valvular disease increases afterload

HF affects 5.7 Million: 3.1 M men, 2.6 M women (self-report, age 20yo, NHANES2008)

Lifetime risk 20% (40yo, Framingham[FHS]) Hospitalizations > 1 M / year Prevalence and Incidence of HF increases with age

670,000 new cases age 45yo (FHS) 56,000 deaths; 1 in 9 deaths (NCHS)

50% diagnosed w/ HF die within 5 yrs

(Olmsted)

Roger V et al. Heart Disease and Stroke Statistics2011 Update. Circulation 2011;123(4):e18-

 The heart is not pumping as well as it should Usually, the heart has been weakened by an underlying condition
Blocked arteries MI High blood pressure Infections Heart valve abnormalities

 Heart failure can involve the left or right side of the heart or both Usually the left side is affected first Heart failure occurs when either side of the heart cannot keep up with the flow of blood

 What

is Heart Failure?

 Involves the left ventricle (lower chamber) of the heart Systolic failure
The heart looses its ability to contract or pump blood into the circulation

Diastolic failure
The heart looses its ability to relax because it becomes stiff Heart cannot fill properly between each beat

Systolic failure- most common cause

Hallmark finding: Dec. in *left ventricular ejection fraction (EF)
Due to

Impaired contractile function (e.g., MI) Increased afterload (e.g., hypertension) Cardiomyopathy Mechanical abnormalities (e.g., valve disease)

Diastolic failure
Impaired ability of ventricles to relax and fill during diastole > dec. stroke volume and CO Diagnosis based on presence of pulmonary congestion, pulmonary hypertension, ventricular hypertrophy normal ejection fraction (EF)

Mixed systolic and diastolic failure

Seen in disease states such as dilated cardiomyopathy (DCM) Poor EFs (<35%) High pulmonary pressures

Biventricular failure (both ventricles may be dilated and have poor filling and emptying capacity)

 Systolic and diastolic heart failure are treated with different types of medications In both types, blood may back up in the lungs causing fluid to leak into the lungs (pulmonary edema) Fluid may also build up in tissues throughout the body (edema)

American Heart Assn-Media files Animations

Pathophysiology A. Cardiac compensatory mechanisms

1.tachycardia 2.ventricular dilation-Starlings law 3.myocardial hypertrophy

Hypoxia leads to dec. contractility

B. Homeostatic Compensatory mechanisms Sympathetic Nervous System 1. Vascular system- norepinephrine- vasoconstriction 2. Kidneys 3. Liver- stores venous volume Counter-regulatory A. Dec. CO and B/P > renin angiotensin release B. Aldosterone release > Na and H2O retention

Inc. Na > release of ADH (diuretics) Release of atrial natriuretic factor > Na and H20 excretion,

Compensatory mechanisms- activated to maintain adequate cardiac output

Neurohormonal responses: Endothelin -stimulated by ADH, catecholamines, and angiotensin II >

Arterial vasoconstriction Inc. in cardiac contractility Hypertrophy

Compensatory mechanisms- activated to maintain adequate CO

Neurohormonal responses: Proinflammatory cytokines (e.g., tumor necrosis factor)
Released by cardiac myocytes in response to cardiac injury Depress cardiac function > cardiac hypertrophy, contractile dysfunction, and myocyte cell death

Compensatory mechanisms- activated to maintain adequate CO

Neurohormonal responses: Over time > systemic inflammatory response > results

Cardiac wasting Muscle myopathy Fatigue

**Counter regulatory processes

Natriuretic peptides: atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP)- *also dx test for HF
Released in response to increased in atrial volume and ventricular pressure Promote venous and arterial vasodilation, reduce preload and afterload Prolonged HF > depletion of these factors

Compensatory mechanisms- activated to maintain adequate CO

Neurohormonal responses: Over time > systemic inflammatory response > results

Cardiac wasting Muscle myopathy Fatigue

Counter regulatory processes

Natriuretic peptides- endothelin and aldosterone antagonists

Enhance diuresis Block effects of the RAAS

Natriuretic peptides- inhibit development of cardiac hypertrophy; may have antiinflammatory effects

Decreased contractility Increased preload (volume) Increased afterload (resistance) **Ventricular remodeling

Ventricular hypertrophy Ventricular dilation

Result of Compensator y Mechanisms > Heart Failure

Heart Failure Explained

Aurigemma GP, Gaasch WH. NEJM 2004;351:1097105.

Coronary artery disease (ischemic cardiomyopathy) 2/3 Hypertension (hypertensive cardiomyopathy) Valvular disease (valvular CM) Infectious (e.g., viral myocarditis, Chagas) Cardiotoxins (e.g., alcohol, chemotherapy) Infiltrative (e.g., amyloidosis, sarcoidosis, hemochromatosis, Wilsons) Peripartum CM Stress-induced CM Genetic (Familial) Idiopathic (Dilated) CM

 Usually occurs as a result of left heart failure The right ventricle pumps blood to the lungs for oxygen Occasionally isolated right heart failure can occur due to lung disease or blood clots to the lung (pulmonary embolism)

 Usually a chronic disease The heart tries to compensate for the loss in pumping function by:
Developing more muscle mass Enlarging Pumping faster

Worsening the HF

 Health conditions that either damage the heart or make it work too hard
Coronary artery disease Heart attack High blood pressure Abnormal heart valves Heart muscle diseases (cardiomyopathy) Heart inflammation (myocarditis)

Congenital heart defects Severe lung disease Diabetes Severe anemia Overactive thyroid gland (hyperthyroidism) Abnormal heart rhythms

 Coronary artery disease

Cholesterol and fatty deposits build up in the hearts arteries Less blood and oxygen reach the heart muscle This causes the heart to work harder and occasionally damages the heart muscle

 Heart attack
An artery supplying blood to the heart becomes blocked Loss of oxygen and nutrients damages heart muscle tissue causing it to die Remaining healthy heart muscle must pump harder to keep up

 High blood pressure

Uncontrolled high blood pressure doubles a persons risk of developing heart failure Heart must pump harder to keep blood circulating Over time, chamber first thickens, then gets larger and weaker

 Abnormal heart valves Heart muscle disease

Damage to heart muscle due to drugs, alcohol or infections

Congenital heart disease Severe lung disease

 Diabetes
Tend to have other conditions that make the heart work harder Obesity Hypertension High cholesterol

 Severe anemia
Not enough red blood cells to carry oxygen Heart beats faster and can become overtaxed with the effort

Hyperthyroidism
Body metabolism is increased and overworks the heart

Abnormal Heart Rhythm

If the heart beats too fast, too slow or irregular it may not be able to pump enough blood to the body

~25% in HF population
Etiology: hemodilution, Fe or Epo deficiency, CKD

1-g/dL Hgb reduction associated with a 20% increase in risk of death

Tang WH et al, JACC 2008;51:569-576; Anand I et al, Circulation 2004;110:149-154

Treatment is relatively easy

Iron supplementation IV iron (short-term) Erythropoiesis-stimulating agents (short term)

 Shortness of Breath (dyspnea)

WHY?
Blood backs up in the pulmonary veins because the heart cant keep up with the supply an fluid leaks into the lungs

SYMPTOMS
Dyspnea on exertion or at rest Difficulty breathing when lying flat Waking up short of breath

 Persistent Cough or Wheezing

WHY?
Fluid backs up in the lungs

SYMPTOMS
Coughing that produces white or pink blood-tinged sputum

 Edema
WHY?
Decreased blood flow out of the weak heart Blood returning to the heart from the veins backs up causing fluid to build up in tissues

SYMPTOMS
Swelling in feet, ankles, legs or abdomen Weight gain

 Tiredness, fatigue
WHY?
Heart cant pump enough blood to meet needs of bodies tissues Body diverts blood away from less vital organs (muscles in limbs) and sends it to the heart and brain

SYMPTOMS
Constant tired feeling Difficulty with everyday activities

 Lack of appetite/ Nausea

WHY?
The digestive system receives less blood causing problems with digestion

SYMPTOMS
Feeling of being full or sick to your stomach

 Confusion/ Impaired thinking

WHY?
Changing levels of substances in the blood ( sodium) can cause confusion

SYMPTOMS
Memory loss or feeling of disorientation Relative or caregiver may notice this first

 Increased heart rate

WHY?
The heart beats faster to make up for the loss in pumping function

SYMPTOMS
Heart palpitations May feel like the heart is racing or throbbing

Hunt SA et al. ACC/AHA Guidelines 2005 & 2001; Circulation 2001;104:2996. Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890

Class

% of Symptoms patients
35% 35% 25% 5% No symptoms or limitations in ordinary physical activity Mild symptoms and slight limitation during ordinary activity Marked limitation in activity even during minimal activity. Comfortable only at rest Severe limitation. Experiences symptoms even at rest

I II III IV

Electrocardiogram (ECG) may show acute ischaemia, arrhythmias, left ventricular hypertrophy, left bundle branch block, or prior MI. Heart failure is unlikely if the ECG is normal, and the diagnosis should be reconsidered in this situation. Chest X-ray (CXR)
pulmonary vascular congestion (upper lobe diversion), pulmonary oedema effusions cardiomegaly

Cardiac function/structure
ECHO (Cardiac MRI, MUGA)

Etiology
R/O CAD: cath vs stress vs CT Serologies: TSH, ANA, Ferritin, HIV, SPEP/UPEP Cardiac MRI Family Hx: Genetic testing?

Stem cells? Hemofiltration?

ARB, H/I in some. ICD

all
Jessup M, Brozena S. NEJM 2003;348:2007

Guidelines
ACC/AHA: 1995, 2001, 2005, 2009 HFSA: 1999, 2006, 2010

Medications
Diuretics, ACE inhibitors* &/or Angiotensin receptor blockers* &/ or Hydralazine/Nitrates*, Beta-blockers*, Aldosterone antagonists*, Digoxin

Electrophysiology (EP) Devices

Implantable cardioverter defibrillator (ICD) Biventricular pacemaker (CRT)

Surgery
Revascularization Ventricular restoration (Dor procedure) Mitral valve surgery Cardiac transplantation Mechanical circulatory support (VAD)

, B-blockers

Kittleson MM, Kobashigawa JA, Circulation 2011;123:1569-1574

Treat the cause Combination of diuretic therapy and ACE-I

If ACE-I is contraindicated use vasodilators

Add beta blocker if the patient was stabilized

Start with low dose

Spironolactone has shown 30% reduction in mortality when administered with the conventional therapy If the above drugs dont relieve the symptoms use digoxin
Positive inotropic agents must be used for short time

If the patient condition become worse make surgery intervention

Preload reduction: reduction of excess plasma volume and edema fluid Afterload reduction: lowered blood pressure

Thiazide
For mild fluid retention

Furosemide
More effective than thiazide Rapid onset and short duration

Potassium sparing diuretics

Use to along with the above diuretics to prevent electrolyte imbalance Spironolactone have beneficial effect on heart remodeling

Aldosterone antagonist, K-sparing diuretic Prevention of aldosterone effects on:

Kidney Heart

Aldosterone inappropriately elevated in CHF Mobilizes edema fluid in heart failure Prevention of hypokalemia induced by loop diuretics (protection against digitalis toxicity?) Prolongs life in CHF patients

First line treatment Lower the morbidity and mortality rate among HF pts Afterload reduction Preload reduction Reduction of facilitation of sympathetic nervous system Reduction of cardiac hypertrophy

Standard -blockers:
Reduction in damaging sympathetic influences in the heart (tachycardia, arrhythmias, remodeling) inhibition of renin release

Carvedilol:
Beta blockade effects peripheral vasodilatation via 1-adrenoceptor blockade (carvedilol)

ACE-I

Enalapril (Vasotec) 10 mg bid Captopril (Capoten) 50 mg tid* Ramipril (Altace) 5 mg bid Lisinopril (Prinivil, Zestril) 20 mg qd Trandolapril (Mavik) 4 mg qd Quinapril (Accupril) 20-40 mg bid

BB

Bisoprolol (Zebeta) 10 mg qd Carvedilol (Coreg) 25-50 mg bid ** Metoprolol XL/CR (Toprol XL) 200 mg qd Metoprolol (Lopressor) 100 mg bid Atenolol (Tenormin) 100 mg qd
*affected by food, ** depends on weight no mortality data, not in guideline

 Mechanism of action: reduce preload and afterload Sodium nitroprusside Hydralazine Nitrates Alpha1 blocker Ca2+ channel blockers

must be avoided

1.

Cardiac glycosides:
Digitalis derivatives :
Digoxin Digitoxin Ouabain

Nondigitalis derivatives:

Congestive Heart Failure Atrial fibrillation Atrial flutter

cardiac output cardiac efficiency heart rate cardiac size

NO survival benefit

Restoration of baroreceptor sensitivity Reduction in sympathetic activity increased renal perfusion, with edema formation Increase parasympathetic outflow

Digoxin has a long enough half life (2436 hr.) and high enough bioavailability to allow once daily dosing Digoxin has a large volume of distribution and dose must be based on lean body mass Increased cardiac performance can increase renal function and clearance of digoxin Eubacterium lentum

Cardiac AV block Bradycardia Ventricular extrasystole Arrhythmias CNS toxicity Delirium Confusion and somnolence GI Anorexia ,nausea and vomitting Blurred vision Tendency to yellow-green vision Photophobia K+ Digitalis competes for K binding at Na/K ATPase Hypokalemia: increase toxicity Hyperkalemia: decrease toxicity Mg2+ Hypomagnesemia: increases toxicity Ca2+ Hypercalcemia: increases toxicity

Bile resins or activated charcoal Atropine: advanced heart block KCl: increased automaticity Antiarrythmics: ventricular arrhythmias Fab antibodies: toxic serum concentration; acute toxicity

Amrinone Milrinone

PDE 3 inhibitor

Inhibition of type III phosphodiesterase increase intracellular cAMP activation of protein kinase A o Ca2+ entry through L type Ca channels o inhibition of Ca2+ sequestration by SR increase cardiac output decrease peripheral vascular resistance short term support in advanced cardiac failure

Cardiac arrhythmias GI: Nausea and vomiting Sudden death

Dobutamin e Dopamine

Beta 1 agonist Administered as IV infusion Used in acute HF Can induce arrhythmias Stimulation of cardiac adrenoceptors: 1 inotropy > chronotropy peripheral vasodilatation myocardial oxygen demand Dobutamine: management of acute failure only

Stimulation of peripheral postjunctional D1 and prejunctional D2 receptors Splanchnic and renal vasodilatation Dopamine: restore renal blood in acute failure

Dobutamine
Tolerance Tachycardia

Dopamine
tachycardia arrhythmias peripheral vasoconstriction if given at high doses

Not followed as standard regimen only in pts with prior embolic events

Treatment options
Not often used in heart failure unless there is a correctable problem Coronary artery bypass Angioplasty Valve replacement Defibrillator implantation Heart transplantation Left ventricular assist device (LVAD)