Cardiovascular disorders

08/20/2014 1Cardiovascular Disorders

PHARMACOTHERAPY

CARDIOVASCULAR DISORDERS

Lecturer: Abdiaziz Sh: Farah


Cardiovascular Disorders


HEART FAILURE

08/20/2014Cardiovascular Disorders 4

Introduction

In the West, cardiovascular disease is the most common cause of premature

death in men, and a frequent cause of disability. Factors such as smoking and diet

are strongly implicated, so much of this illness is preventable. If health

professionals understand the mechanisms of the various disease processes it is

easier for them to help patients avoid or cope with these illnesses.

Cardiovascular disease (CVD) and its treatment frequently causes considerable

confusion because there are a number of closely related conditions and a wide

range of drugs, many of which can be used in more than one condition.

It is the aim of this chapter to explain how an understanding of the principles of

haemodynamics in particular can clarify not only the relationship between

various cardiovascular diseases but also common threads running through their

pharmacotherapy


The first section discusses some important general principles of the normal

function of the cardiovascular system.

We will first consider the cardiovascular system simply as a closed system of

pump, tubes and fluid designed to perfuse the tissues.

We then discuss energy handling in cardiac muscle, its oxygen demand and its

oxygen supply. The physiology of the vascular endothelium and the

neurohormonal control of cardiovascular function must also be considered.

This approach allows predictions to be made about how the cardiovascular

system responds to normal and abnormal circumstances, and how drugs can

affect its function.


Heart FailureHeart failure (HF) is defined as the inadequate ability of the heart to pump enough blood to meet

the blood flow and metabolic demands of the body.

High-output HF is characterized by an inordinate increase in the body’s metabolic demands, which

outpaces an increase in cardiac output(CO) of a generally normally functioning heart.

More commonly, HF is a result of low CO secondary to impaired cardiac function. The term “heart

failure” will refer to low-output HF for purposes of this chapter Heart failure is a clinical syndrome

characterized by a history of specific signs and symptoms related to congestion and hypoperfusion.

As HF can occur in the presence or absence offluid overload, the term “heart failure” is preferred

over the former term “congestive heart failure.”

Heart failure results from any structural or functional cardiac disorder that impairs the ability of the

ventricle to fill with or eject blood.

Many disorders such as those of the pericardium, epicardium, endocardium, or great vessels may

lead to HF, but most patients develop symptoms due to impairment in left ventricular (LV)

myocardial function.


EPIDEMIOLOGYHeart failure is a major public health concern affecting approximately five illion

people in the United States. An additional 550,000 new cases are diagnosed each

year. Heart failure manifests most commonly in adults over the age of 60.

The growing

prevalence of HF corresponds to:

(1)better treatment of patients with acute myocardial infarctions (MIs) who will

survive to develop HF later in life, and

(2) (2) the increasing proportion of older adults due to the aging “baby boomer”

population.

The relative incidence of HF is lower in women compared to men, but there is a

greater prevalence in women overall due to their longer life expectancy. Acute

heart failure accounts for 12 to 15 million office visits per year and 6.5 million

hospitalizations annually. 08/20/2014 8Cardiovascular Disorders

ETIOLOGYHeart failure is the eventual outcome of numerous cardiac diseases or disorders.

Heart failure can be classified by the primary underlying etiology as ischemic or

non ischemic, with 70% of HF related to ischemia.

❶The most common causes of HF are CAD, hypertension, and dilated

cardiomyopathy.

Coronary artery disease resulting in an acute MI and reduced ventricular function is

a common presenting history.

Non-ischemic etiologies include hypertension, viral illness, thyroid disease,

excessive alcohol use, illicit drug use, pregnancy-related heart disease, familial

congenital disease, and valvular disorders such as mitral or tricuspid valve

regurgitation or stenosis.


Causes of Heart Failure

Systolic Dysfunction (Decreased Contractility)

Reduction in muscle mass (e.g., myocardial infarction)

Dilated cardiomyopathies

Ventricular hypertrophy

Pressure overload (e.g., systemic or pulmonary hypertension, aortic or

pulmonic valve stenosis)

Volume overload (e.g., valvular regurgitation, shunts, highoutput states)


Diastolic Dysfunction (Restriction in Ventricular Filling)

Increased ventricular stiffness

Ventricular hypertrophy (e.g., hypertrophic cardiomyopathy, other examples

above)

Infiltrative myocardial diseases (e.g., amyloidosis, sarcoidosis, endomyocardial

fibrosis)

Myocardial ischemia and infarction

Mitral or tricuspid valve stenosis

Pericardial disease (e.g., pericarditis, pericardial tamponade)


PATHOPHYSIOLOGYA basic grasp of normal cardiac function sets the stage for understanding the

pathophysiologic processes leading to HF and selecting appropriate therapy for HF.

Cardiac output is defined as the volume of blood ejected per unit of time (liters

per minute) and is a major determinant of tissue perfusion.

Cardiac output is the product of heart rate (HR) and stroke volume

(SV): CO = HR×SV. The following describes how each parameter relates to CO.

Heart rate is controlled by the autonomic nervous system, where sympathetic

stimulation of β-adrenergic receptors results in an increase in HR and CO.

Stroke volume is the volume of blood ejected with each systole.

Stroke volume is determined by factors regulating preload, afterload, and

contractility.

Preload is a measure of ventricular filling pressure, or the volume of blood in the

left ventricle (also known as LV end diastolic volume).08/20/2014 12Cardiovascular Disorders

Compensatory MechanismsIn the setting of a sustained loss of myocardium, a number of mechanisms aid the

heart when faced with an increased hemodynamic burden and reduced CO. They

include the following:

the Frank-Starling mechanism, tachycardia and increased afterload, and cardiac

hypertrophy and remodeling.

Preload and the Frank-Starling Mechanism

In the setting of a sudden decrease in CO, the natural response of the body is to

decrease blood flow to the periphery in order to maintain perfusion to the vital

organs such as the heart and brain.

Therefore, renal perfusion is compromised due to both the decreased CO, as well

as shunting of blood away from peripheral tissues. This results in activation of the

reninangiotensin-aldosterone system (RAAS).

The decrease in renal perfusion is sensed by the juxtaglomerular cells of the

kidneys leading to the release of renin and initiation of the cascade for production

of angiotensin II.


Tachycardia and Increased Afterload

Another mechanism to maintain CO when contractility is low is to

increase heart rate.

This is achieved through sympathetic nervous system (SNS) activation

and the agonist effect of norepinephrine on β-adrenergic receptors in

the heart.

Sympathetic activation also enhances contractility by increasing

cytosolic calcium concentrations.

SV is relatively fixed in HF, thus HR becomes the major determinant of

CO. Although this mechanism increases CO acutely, the chronotropicand

inotropic responses to sympathetic activation increase myocardial

oxygen demand, worsen underlying ischemia, contribute to

proarrhythmia, and further impair both systolic and diastolic function.08/20/2014 14Cardiovascular Disorders

Cardiac Hypertrophy and Remodeling

Models of Heart Failure

Neurohormonal Model

Cardiorenal Model

Proinflammatory Cytokines


Precipitating and Exacerbating Factors in

Heart Failure

Heart failure patients exist in one of two clinical states. When

a patient’s volume status and symptoms are stable, their HF

condition is said to be “compensated.” In situations of volume

overload or other worsening symptoms, the patient is considered

“decompensated.” Acute decompensation can be precipitated by

numerous etiologies that can be grouped into cardiac,

metabolic, or patient-related causes


CLINICAL PRESENTATION AND DIAGNOSIS OF CHRONIC HEART

FAILUREGeneral

Patient presentation may range from asymptomatic to cardiogenic shock

Symptoms

Dyspnea, particularly on exertion

Orthopnea

Shortness of breath (SOB)

Paroxysmal nocturnal dyspnea

Exercise intolerance

Tachypnea

Cough

Fatigue

Nocturia and/or polyuria

Hemoptysis

Abdominal pain

Anorexia

Nausea

Bloating

Ascites

Mental status changes

Weakness

Lethargy08/20/2014 18Cardiovascular Disorders

Signs

Pulmonary rales

Pulmonary edema

S3 gallop

Pleural effusion

Cheyne-Stokes respiration

Tachycardia

Cardiomegaly

Peripheral edema (e.g., pedal

edema, which is swelling of

feet and ankles)

Jugular venous distension (JVD)

Hepatojugular reflex(HJR

Hepatomegaly

Cyanosis of the digits

Pallor or cool extremities


Laboratory Tests

BNP greater than 100 pg/mL (greater than 100 ng/L) or N-terminal proBNP

(NT-proBNP) greater than 300 pg/mL (greater than 300 ng/L or greater than

35.4 pmol/L)

Electrocardiogram (ECG): May be normal or could show numerous

abnormalities including acute ST-T–wave changes from myocardial ischemia,

atrial fibrillation, bradycardia, and LV hypertrophy.

Serum creatinine: May be increased owing to hypoperfusion; preexisting renal

dysfunction can contribute to volume overload.

Complete blood count: Useful to determine if heart failure is due to reduced

oxygen-carrying capacity.

Chest x-ray: Useful for detection of cardiac enlargement, pulmonary edema,

and pleural effusions.

Echocardiogram: Used to assess LV size, valve function, pericardial effusion,

wall motion abnormalities, and ejection fraction.


TREATMENT OF CHRONIC HEART FAILURE

Desired Therapeutic Outcomes

There is no cure for HF.

❺The general management goals for chronic HF include preventing the onset of clinical symptoms or reducing symptoms, preventing or reducing hospitalizations, slowing progression of the disease, improving quality of life, and prolonging survival.

The ACC/AHA staging system described earlier provides a guide for application of these goals based on the clinical progression of HF for a given patient. The goals are additive as one moves from stage A to stage D.

For stage A, risk factor management is the primary goal.

Stage B includes the addition of pharmacologic therapies known to slow the progression of the disease in an attempt to prevent the onset of clinical symptoms.

Stage C involves the use of additional therapies aimed at controlling symptoms and decreasing morbidity.


OUTCOME EVALUATION OF CHRONIC HEART FAILURE

FIGURE 3–1. Treatment

algorithm for chronic heart

failure.

ACE, angiotensin-onverting

enzyme;

ARB, angiotensin receptor

blocker;

EF, ejection fraction;

HF, heart failure;

LV, left ventricular;

MI, myocardial infarction;

SOB: shortness of breath.

Table 3–5

describes staging of

heart failure.


ACUTE AND ADVANCED HEART FAILURE

Clinical Presentation and Diagnosis of

Acute Heart Failure

Patients with acute heart failure (AHF) present with symptoms of worsening fluid

retention or decreasing exercise tolerance and fatigue (typically worsening of

symptoms presented in the chronic heart failure clinical presentation text box).

These symptoms reflect congestion behind the failing ventricle and/or

hypoperfusion.

Patients can be categorized into hemodynamic subsets based on assessment of

physical signs and symptoms of congestion and/or hypoperfusion.


Clinical Presentation of Acute Heart Failure

Subset I (Warm and Dry)

Cardiac index (CI) greater than2.2 L/minute per square meter, pulmonary

capillary wedge pressure (PCWP) less than 18 mm Hg

Patients considered well compensated and perfused, without evidence of

congestion

No immediate interventions necessary except optimizing oral medications and

monitoring

Subset II (Warm and Wet)

CIgreater than2.2 L/minute per square meter, PCWP greater thanor equal to

18 mm Hg

Patients adequately perfused and display signs and symptoms of congestion

Main goal is to reduce preload (PCWP) carefully with loop diuretics and

vasodilators


Subset III (Cool and Dry)

CIless than 2.2 L/minute per square meter, PCWP less than 18 mm Hg

Patients are inadequately perfused and not congested

Hypoperfusion leads to increased mortality, elevating death rates four-fold compared to those who are adequately perfused

Treatment focuses on increasing CO with positive inotropic agents and/or replacing intravascular fluids

Fluid replacement must be performed cautiously, as patients can rapidly become congested

Subset IV (Cool and Wet)

CIless than 2.2 L/minute per square meter, PCWP greater than 18 mm Hg

Patients are inadequately perfused and congested

Classified as the most complicated clinical presentation of AHF with the worst prognosis

Most challenging to treat; therapy targets alleviating signs and symptoms of congestion by increasing CI as well as reducing PCWP, while maintaining adequate mean arterial pressure

Treatment involves a delicate balance between diuretics, vasodilators, and inotropic agents

Use of vasopressors is sometimes necessary to maintain blood pressure08/20/2014 31Cardiovascular Disorders

TREATMENT OF ACUTE HEART FAILURE

Desired Therapeutic Outcomes

The goals of therapy for AHF are to:

(1) correct the underlying precipitating factor(s);

(2) (2) relieve the patient’s symptoms;

(3) (3) improve hemodynamics;

(4) (4) optimize a chronic oral medication regimen; and

(5) (5) educate the patient, reinforcing adherence to lifestyle modifications and

the drug regimen. The ultimate goal for a patient hospitalized for AHF is the

return to a

compensated HF state and discharge to the outpatient setting on

oral medications.


Reference

pharmacotherapy_principles 2007-mcgraw-hill


Cardiovascular disorders

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