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 Failure
Heart 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.

EPIDEMIOLOGY
Heart 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

ETIOLOGY
Heart 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)

PATHOPHYSIOLOGY
A 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 Mechanisms
In 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
FAILURE
General
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
 Lethargy

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 pressure

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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