Hypertensive Heart Disease-student

7/28/2019 Hypertensive Heart Disease-student

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MODULE

PATHOLOGY OF

CARDIOVASCULAR SYSTEM

Hypertensive Heart

Disease(For Teacher)

BRAWIJAYA UNIVERSITY

FACULTY OF MEDICINE


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TEACHER GUIDANCE

Course Period : 6 th Semester

Course Content : Cardiovascular

Module : Hypertensive heart disaease

1. Contributor(s)

Cholid Tri Tjahjono

2. Competency Area

This module is a part of the elaboration of the area of competence 3 of the Indonesian

Doctor Competencies i.e. The Scientific-Base of Medical Sciences .

3. Competency Component

To introduce the cardiovascular diseases in terms of their basic pathophysiologic

mechanisms; to discuss hypertensive heart disease and other clinical features in the

context of this diseases; to incorporate pertinent laboratory tests and ancillary studies intoclinical problem solving; and to provide a solid background and understanding of the

pharmacologic agents and non-pharmacologic interventions used to treat hypertensive

heart disease.

4. Clinical Competence

Be able to recognize and place the clinical pictures of hypertensive heart disease.

5. Learning Objectives

At the end of the Teaching learning Process of this Module, the: Students should be able to:

Review the normal anatomy and physiology of the heart and cardiovascular system. Assess the signs and symptoms associated with hypertensive heart disease..

Incorporate laboratory data into the assessment of a patient with hypertensive heart disease


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Correlate radiographic, ECG and echocardiographic findings with hypertensive heart

disease. Characterize the classic pathologic features of the cardiovascular disorders discussed in this

module.

Discuss the goals of therapy based on the underlying pathophysiological condition.

Explain how the mechanisms of action of the cardiovascular drugs lead to their therapeuticeffect.

Identify the most common side effects and toxicities of each class of cardiovascular drugs.

6. Lecture Description

This module is a part of Module on Cardiovascular system integratedly designed for medical

student of the 6th semester through Teaching-Learning Process in the 9th Bloc both in Lecture

and Small Group Discussion. This part of Module will facilitate the student a basicunderstanding of the cardiovascular disease.

7. Overview

Hypertensive heart disease

Introduction

Uncontrolled and prolonged elevation of blood pressure (BP) can lead to a variety of changes inthe myocardial structure, coronary vasculature, and conduction system of the heart. These

changes in turn can lead to the development of left ventricular hypertrophy (LVH), coronary

artery disease, various conduction system diseases, and systolic and diastolic dysfunction of the

myocardium, which manifest clinically as angina or myocardial infarction, cardiac arrhythmias(especially atrial fibrillation), and congestive heart failure (CHF). Thus, hypertensive heart

disease is a term applied generally to heart diseases, such as LVH, coronary artery disease,

cardiac arrhythmias, and CHF, that are caused by direct or indirect effects of elevated BP.Although these diseases generally develop in response to chronically elevated BP, marked and

acute elevation of BP can also lead to accentuation of an underlying predisposition to any of the

symptoms traditionally associated with chronic hypertension.

Pathophysiology

The pathophysiology of hypertensive heart disease is a complex interplay of varioushemodynamic, structural, neuroendocrine, cellular, and molecular factors. On the one hand, these

factors play integral roles in the development of hypertension and its complications; on the other

hand, elevated BP itself can modulate these factors. Elevated BP leads to adverse changes incardiac structure and function in 2 ways: directly by increased afterload and indirectly by

associated neurohormonal and vascular changes. Elevated 24-hour ambulatory BP and nocturnal

BP have been demonstrated to be more closely related to various cardiac pathologies, especiallyin African Americans. The pathophysiologies of the various cardiac effects of hypertension

differ and are described in this section.


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Left ventricular hypertrophy

Of patients with hypertension, 15-20% develops LVH. The risk of LVH is increased 2-fold byassociated obesity. The prevalence of LVH based on electrocardiogram (ECG) findings, which

are not a sensitive marker at the time of diagnosis of hypertension, is variable. Studies have

shown a direct relationship between the level and duration of elevated BP and LVH.

LVH, defined as an increase in the mass of the left ventricle (LV), is caused by the response of

myocytes to various stimuli accompanying elevated BP. Myocyte hypertrophy can occur as acompensatory response to increased afterload. Mechanical and neurohormonal stimuli

accompanying hypertension can lead to activation of myocardial cell growth, gene expression (of

which some occurs primarily in fetal cardiomyocytes), and, thus, to LVH. In addition, activation

of the renin-angiotensin system, through the action of angiotensin II on angiotensin I receptors,leads to growth of interstitium and cell matrix components. In summary, the development of

LVH is characterized by myocyte hypertrophy and by an imbalance between the myocytes and

the interstitium of the myocardial skeletal structure.

Various patterns of LVH have been described, including concentric remodeling, concentricLVH, and eccentric LVH. Concentric LVH is an increase in LV thickness and LV mass with

increased LV diastolic pressure and volume, commonly observed in persons with hypertension

and which is a marker of poor prognosis in these patients. Compare this with eccentric LVH, inwhich LV thickness is increased not uniformly but at certain sites, such as the septum. While the

development of LVH initially plays a protective role in response to increased wall stress to

maintain adequate cardiac output, later it leads to the development of diastolic and, ultimately,

systolic myocardial dysfunction.

Left atrial abnormalities

Frequently underappreciated, structural and functional changes of the left atrium (LA) are verycommon in patients with hypertension. The increased afterload imposed on the LA by the

elevated LV end-diastolic pressure secondary to increased BP leads to impairment of the LA andLA appendage function plus increased LA size and thickness. Increased LA size accompanying

hypertension in the absence of valvular heart disease or systolic dysfunction usually implies

chronicity of hypertension and may correlate with the severity of LV diastolic dysfunction. Inaddition to these structural changes, these patients are predisposed to atrial fibrillation. Atrial

fibrillation, with loss of atrial contribution in the presence of diastolic dysfunction, may

precipitate overt heart failure.

Valvular disease

Although valvular disease does not cause hypertensive heart disease, chronic and severe

hypertension can cause aortic root dilatation, leading to significant aortic insufficiency. Somedegree of hemodynamically insignificant aortic insufficiency is often found in patients with

uncontrolled hypertension. An acute rise in BP may accentuate the degree of aortic insufficiency,

with return to baseline when BP is better controlled. In addition to causing aortic regurgitation,hypertension is also thought to accelerate the process of aortic sclerosis and cause mitral

regurgitation.


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Heart failure

Heart failure is a common complication of chronically elevated BP. Hypertension as a cause ofCHF is frequently underrecognized, partly because at the time heart failure develops, the

dysfunctioning LV is unable to generate the high BP, thus obscuring the etiology of the heart

failure. The prevalence of asymptomatic diastolic dysfunction in patients with hypertension andwithout LVH may be as high as 33%. Chronically elevated afterload and resulting LVH canadversely affect both the active early relaxation phase and late compliance phase of ventricular

diastole.

Diastolic dysfunction is common in persons with hypertension. It is often, but not invariably,

accompanied by LVH. In addition to elevated afterload, other factors that may contribute to the

development of diastolic dysfunction include coexistent coronary artery disease, aging, systolicdysfunction, and structural abnormalities such as fibrosis and LVH. Asymptomatic systolic

dysfunction usually follows. Later in the course of disease, the LVH fails to compensate by

increasing cardiac output in the face of elevated BP and the left ventricular cavity begins to dilateto maintain cardiac output. As the disease enters the end stage, LV systolic function decreases

further. This leads to further increases in activation of the neurohormonal and renin-angiotensinsystems, leading to increases in salt and water retention and increased peripheralvasoconstriction, eventually overwhelming the already compromised LV and progressing to the

stage of symptomatic systolic dysfunction.

Apoptosis, or programmed cell death, stimulated by myocyte hypertrophy and the imbalance

between its stimulants and inhibitors, is considered to play an important part in the transition

from compensated to decompensated stage. The patient may become symptomatic during theasymptomatic stages of the LV systolic or diastolic dysfunction, owing to changes in afterload

conditions or to the presence of other insults to the myocardium (eg, ischemia, infarction). A

sudden increase in BP can lead to acute pulmonary edema without necessarily changing the LV

ejection fraction.Generally, development of asymptomatic or symptomatic LV dilatation ordysfunction heralds rapid deterioration in clinical status and markedly increased risk of death. In

addition to LV dysfunction, right ventricular thickening and diastolic dysfunction also develop asresults of septal thickening and LV dysfunction.

Myocardial ischemia

Patients with angina have a high prevalence of hypertension. Hypertension is an established riskfactor for the development of coronary artery disease, almost doubling the risk. The development

of ischemia in patients with hypertension is multifactorial.

Importantly, in patients with hypertension, angina can occur in the absence of epicardial

coronary artery disease. The reason is 2-fold. Increased afterload secondary to hypertension leads

to an increase in left ventricular wall tension and transmural pressure, compromising coronaryblood flow during diastole. In addition, the microvasculature, beyond the epicardial coronary

arteries, has been shown to be dysfunctional in patients with hypertension and it may be unable

to compensate for increased metabolic and oxygen demand.

The development and progression of arteriosclerosis, the hallmark of coronary artery disease, isexacerbated in arteries subjected to chronically elevated BP. Shear stress associated with


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hypertension and the resulting endothelial dysfunction causes impairment in the synthesis and

release of the potent vasodilator nitric oxide. A decreased nitric oxide level promotes thedevelopment and acceleration of arteriosclerosis and plaque formation. Morphologic features of

the plaque are identical to those observed in patients without hypertension.

Cardiac arrhythmias

Cardiac arrhythmias commonly observed in patients with hypertension include atrial fibrillation,

premature ventricular contractions, and ventricular tachycardia.

The risk of sudden cardiac death is increased. Various mechanisms thought to play a part in thepathogenesis of arrhythmias include altered cellular structure and metabolism, inhomogeneity of

the myocardium, poor perfusion, myocardial fibrosis, and fluctuation in afterload. All of these

may lead to an increased risk of ventricular tachyarrhythmias.

Atrial fibrillation (paroxysmal, chronic recurrent, or chronic persistent) is observed frequently in

patients with hypertension.In fact, elevated BP is the most common cause of atrial fibrillation in

the Western hemisphere. In one study, nearly 50% of patients with atrial fibrillation hadhypertension. Although the exact etiology is not known, left atrial structural abnormalities,

associated coronary artery disease, and LVH have been suggested as possible contributing

factors. The development of atrial fibrillation can cause decompensation of systolic and, moreimportantly, diastolic dysfunction, owing to loss of atrial kick, and it also increases the risk of

thromboembolic complications, most notably stroke.

Premature ventricular contractions, ventricular arrhythmias, and sudden cardiac death are

observed more often in patients with LVH than in those without LVH. The etiology of thesearrhythmias is thought to be concomitant coronary artery disease and myocardial fibrosis.

Frequency

United States

The estimated prevalence of hypertension in 2005 was 35.3 million men and 38.3 million

women. The exact frequency of LVH is unknown. The rate of LVH based on ECG findings is2.9% for men and 1.5% for women. The rate based on echocardiography findings is 15-20%. Of

patients without LVH, 33% have evidence of asymptomatic LV diastolic dysfunction.

According to the Framingham Study, hypertension accounts for about a quarter of heart failurecases.In the elderly population, as many as 68% of heart failure cases are attributed to

hypertension. Community-based studies have demonstrated that hypertension may contribute to

the development of heart failure in as many as 50-60% of patients. In patients with hypertension,the risk of heart failure is increased by 2-fold in men and by 3-fold in women.

Mortality/Morbidity

Mortality and morbidity rates from hypertensive heart disease are higher than those of the

general population and depend on the specific cardiac pathology. Data suggest that increases in


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mortality and morbidity rates are related more to the pulse pressure than the absolute systolic or

diastolic BP levels, but all are important.

Left ventricular hypertrophy: The development of LVH is clearly related to an increase in

the cardiovascular mortality rate. The increased risk of cardiovascular events with LVH

depends on its type. Concentric LVH poses the greatest risk, as much as 30% over a 10-year period in one study, compared with 15% with eccentric remodeling and 9% withoutany LVH. The degree of LVH, as assessed by LV mass index (LVMI), is also related to

the cardiovascular mortality rate, with a relative risk of 1.73 for men and 2.12 for women

for each 50-g/m2 increase in the LVMI over a 4-year period. With LVH, the relative riskof mortality is increased 2-fold in patients with coronary artery disease and 4-fold in

patients without coronary artery disease.

Studies have also shown an increase in the risk of sudden cardiac death in patients withLVH. Regression of the LVMI has been demonstrated with several different

antihypertensive medications. Although not proven, limited data suggest a reduction in

LVH results in a reduction in cardiovascular events. LV diastolic dysfunction: The prognosis of patients with diastolic dysfunction is poor and

is affected by the presence of underlying coronary artery disease. In one study, survival

rates at 3 months, 1 year, and 5 years in patients with heart failure due to diastolic

dysfunction were 86%, 76%, and 46%, respectively. In another study, the 7-yearcardiovascular mortality rate approached 50% in patients with heart failure due to

diastolic dysfunction and concomitant coronary artery disease; some also had

hypertension. Even in patients with asymptomatic diastolic dysfunction due tohypertension, risk of all cause mortality and cardiovascular events is significantly

increased, particularly with an increase in the pulmonary artery wedge pressure. LV

diastolic dysfunction, and the heart failure symptoms associated with it, has been shown

to improve with treatment aimed at lowering BP and reducing LVH. Whether suchtreatment has any effect on the mortality rate is not clear.

LV systolic dysfunction: The mortality rate from heart failure due to systolic LV

dysfunction is high and depends on the symptoms and New York Heart Association

(NYHA) classification. The 5-year mortality rate for patients with heart failure due to

systolic dysfunction approaches 20%, while the 2-year mortality rate in patients withNYHA class IV classification is as high as 50%. Mortality rates have decreased with use

of ACE inhibitors and beta-blockers, which improve LV function.

Race

In the United States, hypertension is more prevalent in African Americans than in Hispanic andnon-Hispanic whites and it is increasing. From 1988-94 to 1999-2002, prevalence in this group

increased from 35.8% to 41.4%. (Prevalence in whites is increasing as well but not as

dramatically.) This difference is attributed to factors other than race because the prevalence of

hypertension among African Americans and whites is the same in the United Kingdom andbecause hypertension is not very common on the African continent. In addition, hypertension is

the most common etiology of heart failure in African Americans in the United States.


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Sex

Systolic BP increases with age. This increase is more marked in men than in women untilwomen reach menopause, when their BP rises more sharply and reaches levels higher than in

men. The prevalence of hypertension is higher in men than in women younger than 55 years but

is higher in women older than 55 years. The prevalence of hypertensive heart disease probablyfollows the same pattern.

Age

BP increases with age, as does the prevalence of hypertensive heart disease, which is affected by

the severity of BP increase.

Clinical

History

Symptoms of hypertensive heart disease depend on the duration, severity, and type of disease. In

addition, the patient may or may not be aware of the presence of hypertension, which is whyhypertension has been named "the silent killer."

Left ventricular hypertrophy: Patients with LVH alone are totally asymptomatic unless

the LVH leads to the development of diastolic dysfunction and heart failure.

Heart failure

o Although symptomatic diastolic heart failure and systolic heart failure are

indistinguishable, the clinical history may be quite revealing. In particular,

individuals who abruptly develop severe symptoms of CHF and rapidly return to

baseline with medical therapy are more likely to have isolated diastolic

dysfunction.

o Heart failure symptoms include the following:

Exertional and nonexertional dyspnea (NYHA classes I-IV)

Orthopnea

Paroxysmal nocturnal dyspnea

Fatigue (more common in systolic dysfunction)

Ankle edema and weight gain

Abdominal pain secondary to congested, distended liver

Altered mentation in severe cases

o Patients can present with acute pulmonary edema due to sudden decompensation

in LV systolic or diastolic dysfunction caused by precipitating factors such as

acute rise in BP, dietary indiscretion, or myocardial ischemia. Patients can


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develop cardiac arrhythmias, especially atrial fibrillation, or they can develop

symptoms of heart failure insidiously over time.

Myocardial ischemia

o Angina, a frequent complication of hypertensive heart disease, is also

indistinguishable from other causes of myocardial ischemia.

o Typical symptoms of angina include substernal chest pain lasting less than 15

minutes (versus >20 min in infarction). Pain is often described in the following

ways:

Heaviness, pressure, squeezing

Radiating to neck, jaw, upper back, or left arm

Provoked by emotional or physical exertion

Relieved with rest or sublingual nitroglycerin

o Patients also may present with atypical symptoms without chest pain, such as

exertional dyspnea or excessive fatigue, commonly referred to as an angina

equivalent. Female patients, in particular, are more likely to present with an

atypical presentation

o The patient may present with chronic stable angina or acute coronary syndrome,

including myocardial infarction without ST-segment elevation and acutemyocardial infarction with ST elevation. Ischemic ECG changes may be found in

individuals presenting with hypertensive crisis in whom no significant coronary

atherosclerosis is detectable by coronary angiography.

o Acute coronary symptoms can be precipitated by a ruptured atherosclerotic plaque

or by an acute and severe rise in BP leading to a sudden increase in transmuralpressure without a change in stability of the plaque.

Cardiac arrhythmias: These can cause a variety of symptoms, including palpitations, near

or total syncope, precipitation of angina, sudden cardiac death, and precipitation of heartfailure, especially with atrial fibrillation in diastolic dysfunction.

Physical

Physical signs of hypertensive heart disease depend on the predominant cardiac abnormality and

the duration and severity of the hypertensive heart disease. Findings from the physicalexamination may be entirely normal in the very early stages of the disease, or the patient mayhave classic signs upon examination. In addition to generalized findings attributable directly to

high BP, the physical examination may reveal clues to a potential etiology of hypertension, such

as truncal obesity and striae in Cushing syndrome, renal artery bruit in renal artery stenosis, andabdominal mass in polycystic kidney disease.

Pulses: The arterial pulses are normal in the early stages of the disease.


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o Rhythm

Regular if the patient is in sinus rhythm

Irregularly irregular if the patient is in atrial fibrillation

o Rate

Normal in patients in sinus rhythm and not in decompensated heart failure

Tachycardic in patients with heart failure and in patients with atrialfibrillation and a rapid ventricular response

o Volume

Normal

Decreased in patients with LV dysfunction

o Additional findings - May include radial-femoral delay if the etiology ofhypertension is coarctation of the aorta

Blood pressure: Systolic and/or diastolic BP is elevated (>140/90 mm Hg). Mean BP and

pulse pressure generally are also elevated. The BP in the upper extremities may be higherthan that in the lower extremities in patients with coarctation of the aorta. BP may be

normal at the time of evaluation if the patient is on adequate antihypertensive

medications or the patient has advanced LV dysfunction and the LV cannot generateenough stroke volume and cardiac output to produce an elevated BP.

Veins: In patients with heart failure, jugular veins may be distended; the predominant

waves depend on the severity of the heart failure and any other associated lesions.

Heart

o Apex: The apical impulse is sustained and nondisplaced in patients without

significant systolic LV dysfunction but with LVH. A presystolic S4 may be felt.

Later in the course of disease, when significant systolic LV dysfunctionsupervenes, the apical impulse is displaced laterally, owing to LV dilatation.

o Right ventricle: A lift is present late in the course of heart failure if significant

pulmonary hypertension develops.

o

Heart sounds: S1 is normal in intensity and character. S2 at the right upper sternalborder is loud because of an accentuated aortic component (A2); it can have a

reverse or paradoxical split due either to increased afterload or to associated left

bundle-branch block (LBBB). S4 frequently is palpable and audible, implying the

presence of a stiffened, noncompliant ventricle due to chronic pressure overloadand LVH. S3 typically is not present initially but is audible in the presence of

heart failure, either systolic or diastolic.


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o Murmurs: An early decrescendo diastolic murmur of aortic insufficiency may be

heard along the mid-to-left parasternal area, especially in the presence of acutely

elevated BP, frequently disappearing once the BP is better controlled. In addition,

an early to mid systolic murmur of aortic sclerosis is commonly audible. A

holosystolic murmur of mitral regurgitation may be present in patients with

advanced heart failure and dilated mitral annulus.

Lungs: Findings upon chest examination may be normal or may include signs of

pulmonary congestion, such as rales, decreased breath sounds, and dullness to percussion

due to pleural effusion.

Abdomen: Abdominal examination may reveal a renal artery bruit in patients with

hypertension secondary to renal artery stenosis, a pulsatile expansile mass of abdominal

aortic aneurysm, and hepatomegaly and ascites due to CHF.

Extremities: Ankle edema may be present in patients with advanced heart failure.

CNS and retina

o CNS examination findings are usually unremarkable unless the patient has had

previous cerebrovascular accidents with residual deficit.

o Examination of the fundi may reveal evidence of hypertensive retinopathy, the

severity of which depends on the duration and severity of hypertension, or earlier

signs of hypertension such as arteriovenous nicking.

o CNS changes may be seen in patients who present with hypertensive emergency.

Causes

The cause of hypertensive heart disease is chronically elevated BP. The causes of elevated BPare diverse. In adults, the following causes should be considered:

Essential hypertension accounts for 90% of cases of hypertension in adults.

Secondary causes of hypertension account for the remaining 10% of cases of chronically

elevated BP. These include the following:

o Renal causes

Renal artery stenosis

Polycystic kidney disease Chronic renal failure

Intrarenal Vasculitis

o Endocrine causes

Primary hyperaldosteronism


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Pheochromocytoma

Cushing syndrome

Congenital adrenal hyperplasia

Hypothyroidism and hyperthyroidism

Acromegaly

Exogenous hormone (eg, corticosteroids, estrogens), sympathomimetics(including cocaine), monoamine oxidase inhibitors (MAOIs), and

tyramine-containing foods

o Others

Coarctation of aorta

Raised intracranial pressure

Sleep apnea

Isolated systolic hypertension - Can be observed in elderly people, due to

increased stiffness of the vasculature

Isolated systolic hypertension - Can be observed in thyrotoxicosis,

atrioventricular (AV) fistula, aortic regurgitation, beriberi, Paget disease,

and patent ductus arteriosus (ie, due to increase cardiac output secondaryto a hyperdynamic circulation)

Differential diagnosis

Coronary artery atherosclerosis

Other Problems to Be Considered

Hypertrophic cardiomyopathy, Athlete's heart (with LVH), Congestive heart failure due

to other etiologies, atrial fibrillation due to other etiologies, Diastolic dysfunction due to

other etiologies , sleep apnea.

Workup

Laboratory Studies

Recommendations from JNC 7 include the following

Laboratory studies are helpful in establishing the etiology of hypertension, quantitating

severity of target organ damage, and monitoring the adverse effects of therapy.

Blood urea nitrogen (BUN) and creatinine levels are elevated in patients with renal

failure.


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Hypokalemia is found in patients with primary hyperaldosteronism and in patients with

secondary hyperaldosteronism, Cushing disease, and Bartter syndrome. Hypokalemia is

most useful in leading to further diagnostic studies if the patient has not received

diuretics.

Plasma renin activity generally is depressed and serum aldosterone level is elevated in

patients with primary hyperaldosteronism.

Twenty-fourhour urinary catecholamine and metanephrine levels are elevated in patients

with pheochromocytoma.

Elevated 24-hour urinary free cortisol and failure to suppress an early morning serum

cortisol level after an overnight dexamethasone suppression test are observed in patients

with Cushing disease.

Thyrotropin levels may be elevated in patients with hypothyroidism and depressed in

patients with hyperthyroidism.

Other laboratory studies to be ordered depend on clinical judgment regarding the etiology

of hypertension.

Imaging Studies

Chest radiographs may show the following:

o Notching of the undersurface of the ribs - Secondary to the development of

collateral circulation in coarctation of the aorta

o Cardiomegaly - Secondary to LV dilatation, in late stages of the disease

o Cephalization of pulmonary blood flow, Kerley B lines, and alveolar infiltrates -

In patients with elevated LV end-diastolic pressure and pulmonary congestion

o Blunting of costophrenic angle - In patients who develop pleural effusion

Computed tomography (CT) scanning, magnetic resonance imaging (MRI), and magnetic

resonance angiography of the abdomen and chest show the presence of adrenal masses orevidence of coarctation of aorta.

CT scanning and MRI of the heart, although not used routinely, have been shown in

experimental studies to quantify LVH.

o Transthoracic echocardiography (TTE) may be very useful

o in identifying features of hypertensive heart disease

o Evidence of LVH

TTE is more sensitive and specific then ECG for diagnosing the presence

of LVH57% for mild and 98% for severe LVH.


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LVH is symmetrical, while the hypertrophy of hypertrophic

cardiomyopathy is asymmetrical. Definition of the LVH based onechocardiography findings is somewhat controversial in the absence of

any criterion standards.

On 2-dimensional and M-mode examination, the interventricular septum is

thickened, as is the posterior wall (>1.1 cm).

LVH is defined quantitatively as an increase in the LV mass or LVMI.

Various formulas have been used to calculate LV mass, each with inherent

drawbacks.

o Evidence of LV diastolic dysfunction as measured by the following:

The transmitral flow velocity pattern, characterized by abnormally

prolonged isovolumic relaxation time, a reversed "E:A" ratio, and a

prolonged deceleration time, is abnormal. The patient may exhibit a

pseudonormal pattern during the transition from the impaired relaxation tothe restrictive filling phase.

The tissue Doppler indices are abnormal. The tissue Doppler profile showsa reversed E:A ratio. This is especially helpful in patients who have a

pseudonormal pattern on transmitral flow velocity Doppler studies.

o Evidence of LV systolic dysfunction

The LV is dilated.

The LV fractional shortening is low.

The LV ejection fraction is low.

Systolic dysfunction is present, which is commonly associated with some

degree of diastolic dysfunction.

o Evidence of LA dilatation

o Evidence of right-sided dilatation: Right-sided chambers may be dilated with

some degree of pulmonary hypertension.

o Evidence of valvular abnormalities, such as aortic sclerosis (on 2-dimensional)

and aortic and mitral insufficiency (on color flow and Doppler examination)

Nuclear imaging may be useful in screening for the presence of coronary artery disease.

Other Tests

Sleep evaluation

Additional tests for excluding other secondary causes of hypertension.

Twelve-lead ECG may show a variety of abnormalities.


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o Evidence of left atrial enlargement - Broad P waves in limb leads and

prominent and wide delayed negative deflection in V1.

o Conduction abnormalities

Of patients with left anterior fascicular block on ECG, 50% had

hypertension in one series.

As many as 70-80% of patients with LBBB have hypertension.

o Evidence of LVH on ECG

The frequency of LVH on ECG at the time of initial diagnosis varies from10-100%; in a recent trial, the frequency was 13%.

The sensitivity of ECG for diagnosing LVH is limited, 30-57% in patients

with severe LVH.

o Other criteria: Various criteria, differing in sensitivity and specificity, have been

used to diagnose LVH, as summarized below. Note that the specificities andsensitivities of all these approaches are far less than those of echocardiography.

The Cornell criteria (most sensitive) are (1) R aVL plus an S wave in V3 ofgreater than 2.8 mV in men and greater than 2 mV in women. The Cornell

and Cornell voltage duration (Cornell voltage multiplied by QRS duration)

criteria have a sensitivity of as high as 95% and a specificity of as high as50-60%. A Cornell voltage duration of greater than 2440 mV/ms -1

particularly identified the highest-risk patients.

The Sokolow-Lyon criteria are an S wave in V1 plus an R wave in V5 or

V6 of greater than 3.5 mV or an R wave in V5 or V6 of greater than 2.6mV. The sensitivity of these criteria is 25%, with a specificity of close to

95%.

The Gubner-Ungerleider criteria are an R wave in I plus an S wave in III

of greater than 2.5 mV.


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Table 1. Romhilt-Estes Criteria (a point score system*) for left ventricular hypertrophy

Voltage Criteria Points

R wave or S wave in any limb lead >0.2 mV or S wave in lead V1 or V2 or R wave in V5

or V6 >0.3 mV

3

LV strain (ST and T waves in direction opposite to QRS direction) without digitalis 3

LV strain (ST and T waves in direction opposite to QRS direction) with digitalis 1

LA enlargement (terminal negativity of P waves in V1 >0.1 mV deep and 0.04 seconds

wide)

3

Left-axis deviation of greater than -30 2

QRS duration greater than 0.09 seconds 1

Intrinsicoid deflection in V5 or V6 >0.05 seconds 1

Voltage Criteria Points

R wave or S wave in any limb lead >0.2 mV or S wave in lead V1 or V2 or R wave in V5

or V6 >0.3 mV

3


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LV strain (ST and T waves in direction opposite to QRS direction) without digitalis 3

LV strain (ST and T waves in direction opposite to QRS direction) with digitalis 1

LA enlargement (terminal negativity of P waves in V1 >0.1 mV deep and 0.04 seconds

wide)

3

Left-axis deviation of greater than -30 2

QRS duration greater than 0.09 seconds 1

Intrinsicoid deflection in V5 or V6 >0.05 seconds 1

*Probable LVH is 4 points; definite LVH is 5 points. The sensitivity of these criteria is 50%,

with a specificity of close to 95%.

Procedures

Cardiac catheterization is used for diagnosis of coronary artery disease and helps assess theseverity of elevated pulmonary artery pressure in patients with heart failure.

Histologic Findings

Gross findings

LVH (concentric) occurs without dilatation of the LV . The ratio of wall thickness to the radiusof the ventricular chamber increases. LV wall thickness may exceed 2 cm, and the heart weight

exceeds 500 g. Dilatation of the ventricular chamber, thinning of the walls, and enlargement of

the external dimensions of the heart occur with the onset of decompensation.

Gross specimen of the heart with concentric left ventricular hypertrophy.

Microscopic findings

The earliest changes of hypertensive heart disease include myocyte enlargement, with an

increase in their transverse diameters.


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Histologic section of the myocardium showing a cross-section of coronary artery affected

by atherosclerosis and myocyte hypertrophy.

At a more advanced stage, cellular and nuclear enlargement (with variation in cell size), loss of

myofibrils, and interstitial fibrosis occur.

Histologic section of an autopsy myocardial specimen from a patient with long-standing

hypertension and associated coronary artery disease. The slide shows myocardial

hypertrophy, contraction bands (typical of left ventricular hypertrophy), and "car box"

nuclei.

Histologic section of the heart showing the hypertrophied myocytes and fibrosisaccompanying left ventricular hypertrophy.

Staging

BP and hypertension itself have been divided into stages.


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Table 2. Stages of Elevated BP and Hypertension According to The Seventh Report of the Joint

National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood

Pressure.

Classification of hypertension

CategorySystolic BP,

mm Hg

Diastolic BP,

mm Hg

Optimal 100

Category Systolic BP,mm Hg

Diastolic BP,mm Hg

Optimal 100

When the BP is more than 20/10 mm Hg above the goal, consideration should be given toinitiating therapy with 2 drugs, either as separate prescriptions or in fixed-dose combinations.

Although hypertensive heart disease typically is not described in various stages, the

disease usually progresses in the following sequence: Increased wall stress leads to LVH,which leads to diastolic LV dysfunction, which can be followed by systolic LV

dysfunction.


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The risks of ventricular ectopy, ventricular arrhythmias, sudden cardiac death, and

cardiovascular mortality are increased in patients once the LVH develops and in patients

with heart failure.

Treatment

Medical Care

The medical care of patients with hypertensive heart disease falls under 2 categoriestreatment

of the elevated BP and prevention and treatment of hypertensive heart disease. According to JNC7, the BP goal should be less than 140/90 mm Hg in patients with uncomplicated

hypertension, less than 130/85 mm Hg in those with diabetes and those with renal disease with

less than 1 gram/24 hr proteinuria, and less than 125/75 in those with renal disease and more than1 gram/24 hr proteinuria.Emerging data support a target blood pressure goal of less than 150/80

mm Hg in patients more than 80 years old. Various treatment strategies include dietary

modifications, regular aerobic exercise, weight loss,and pharmacotherapy directed toward

hypertension, heart failure secondary to diastolic and systolic LV dysfunction, coronary arterydisease, and arrhythmias.

Dietary modifications

Studies have shown that diet and a healthy lifestyle alone or in

combination with medical treatment can lower the BP and decrease thesymptoms of heart failure and can also reverse LVH. Specific diet

recommendations include a diet low in sodium, high in potassium (in

patients with normal renal function), rich in fresh fruits and vegetables,low in cholesterol, and low in alcohol consumption. In a large 2009 cohort

study of women, the following 6 modifiable lifestyle and dietary factors

for hypertension were identified.

A body mass index (BMI) of less than 25

A daily mean of 30 minutes of vigorous exercise

A high score on the Dietary Approaches to Stop Hypertension (DASH)

diet

Modest alcohol intake (up to 10 g/d)

Use of nonnarcotic analgesics less than once per week

Intake of 400 mcg/d or more of supplemental folic acid

oA low-sodium diet, alone or in combination with pharmacotherapy, has been shown by

numerous studies to reduce BP in patients with hypertension, with a more prominent

response in a subset of patients with hypertensionmainly African Americanswith

low renin levels. Restriction of sodium in these patients does not lead to compensatorystimulation of the renin-angiotensin system and thus has a potent antihypertensive

effect. Data also indicates that sodium reduction, previously shown to lower blood


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pressure, may also reduce long-term risk of cardiovascular events. The recommended

daily sodium intake is 50-100 mmol, equivalent to 3-6 g of salt per day, which leads toan average 2-8 mm Hg reduction in BP.

oIn various epidemiological studies, a high-potassium diet has been associated with

lowering of the BP. The mechanism of this action is not clear. Intravenous infusion of

potassium has been shown to cause vasodilatation, which is believed to be mediated by

nitric oxide in the vascular wall. Fresh fruits and vegetables rich in potassium, such asbananas, oranges, avocados, and tomatoes, should be recommended for patients with

normal renal function.

oThe DASH diet has been shown to significantly lower the BP (8-14 mm Hg) in patients

with hypertension regardless of them maintaining a constant sodium content in their

diet. The DASH diet is not only rich in important nutrients and fiber but also includesfoods that contain far more potassium, calcium, and magnesium, than are found in the

average American diet. This diet should be advised in patients with hypertension.

oA heart-healthy diet is part of the secondary prophylaxis in patients with coronary arterydisease and of the primary prophylaxis in patients at high risk for this disease.

oHeavy alcohol consumption has been associated with high BP and an increase in LV

mass. Moderation in alcohol consumption is advised; no more than 1-2 drinks per day

is recommended.

Regular aerobic exercise

o Regular dynamic isotonic (aerobic) exercise, such as walking, running,

swimming, or cycling, has been shown to decrease BP and improvecardiovascular well-being.It also has additional favorable cardiovascular effects,

including improved endothelial function, peripheral vasodilatation, reduced

resting heart rate, improved heart rate variability, and reduced plasma levels of

catecholamines.

o Regular aerobic exercise sessions of at least 30 minutes for most days of the week

can produce an average reduction in BP of 4-9 mm Hg. Isometric and strenuousexercise should be avoided.

Weight reduction

o Obesity has been linked to hypertension and LVH in various epidemiological

studies, with as many as 50% of obese patients having some degree ofhypertension and as many as 60-70% of patients with hypertension being obese.Studies have shown that weight reduction is one of the most effective ways to

reduce BP. A 5-20 mm Hg BP reduction occurs with each 10 kg of weight loss.

o Abdominal adiposity, clinically measured as waist-to-hip ratio and more

accurately assessed by abdominal CT scan, is a particularly sensitive risk factor

for hypertension.


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o Gradual weight reduction (1 kg/wk) should be advised. Pharmacological

interventions to reduce weight should be used with great caution because diet

pills, especially those available over the counter, frequently contain

sympathomimetics. These can raise BP, worsen angina or symptoms of heart

failure, and exacerbate tendencies for cardiac arrhythmias

o Avoid medications such as NSAIDs, sympathomimetics, or MAOIs that can

elevate BP or interfere with antihypertensive therapy.

Pharmacotherapy Treatment of hypertension and hypertensive heart disease can involve the following

classes of antihypertensive medications: thiazide diuretics, beta-blockers and combinedalpha- and beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor

blockers, and direct vasodilators such as hydralazine.

o Thiazide-type diuretics should be used for most patients with uncomplicated

hypertension, either alone or combined with drugs from other classes, according

to the Joint National Committee on Prevention, Detection, Evaluation, andTreatment of High Blood Pressure. Updated recommendations from the JNC

(JNC-8) are expected in 2010.

o Most patients require 2 or more antihypertensive drugs to achieve the BP goal,

and, when the BP is more than 20/10 mm Hg above the goal, consider initiating

treatment with 2 drugs, either as separate prescriptions or in fixed-dose

combinations.

Calcium channel blockers are effective for systolic hypertension in elderlypatients. In a 2008 study, an ACE inhibitor/dihydropyridine calciumchannel blocker combination proved to be superior to the ACE

inhibitor/thiazide diuretic combination in reducing cardiovascular events

in patients with hypertension who were at high risk for such events.

ACE inhibitors are the first choice in patients with diabetes and/or V

dysfunction.

Angiotensin receptor blockers are a reasonable alternative, especially for

patients with adverse effects with ACE inhibitors.

Beta-blockers are the drugs of first choice in patients with heart failure dueto systolic LV dysfunction, patients with ischemic heart disease with or

without a history of myocardial infarction, and in patients withthyrotoxicosis.

Peripheral alpha-channel blockers should be avoided in patients withhypertension in view of recent findings of their adverse effect on

cardiovascular morbidity and mortality rates.


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Central alpha-antagonists have no evidence-based support and have more

adverse effects.

o Intravenous drugs used in patients with a hypertensive emergency include

nitroprusside, labetalol, hydralazine, enalapril, and beta-blockers (avoided inpatients with acutely decompensated heart failure).

o Some evidence shows that peroxisome proliferator-activated receptor gamma

(PPAR) agonist ameliorates oxidative stress and leads to reversal of systemic

hypertension-associated cardiac remodeling in chronic pressure overload

myocardium and LVH.

Treatment of LVH

o LVH, a marker of increased risk of cardiovascular morbidity and mortality,

should be treated aggressively. Whether regression in LVH leads to improvement

in cardiovascular mortality and morbidity rates is not clear, although limited data

support this hypothesis. Data also indicate that regression of electrocardiographicLVH is associated with less hospitalization for heart failure in hypertensive

patients.

o All the medications already listed for the treatment of hypertension have been

shown to reduce LVH. Limited meta-analysis data suggest a slight advantage to

ACE inhibitors.

Treatment of LV diastolic dysfunction

o Certain classes of antihypertensivesACE inhibitors, beta-blockers, and

nondihydropyridine calcium channel blockershave been shown (although not

consistently) to improve echocardiographic parameters in symptomatic andasymptomatic diastolic dysfunction and the symptomatology of heart failure.

o The angiotensin receptor blocker, candesartan, has been shown to decrease

hospitalization in patients with diastolic heart failure.

o Use diuretics and nitrates with caution in patients with heart failure due to

diastolic dysfunction. These drugs may cause severe hypotension byinappropriately decreasing the preload, which is required for adequate LV filling

pressures. If diuretics are indicated, delicate titration is necessary.

o Hydralazine has been shown to cause severe hypotension in patients with heart

failure due to diastolic dysfunction.

o By increasing the intracellular calcium level, digoxin can worsen LV stiffness.

However, a large randomized trial has not shown any increase in mortality rate.

Treatment of LV systolic dysfunction

o Diuretics (predominantly loop diuretics) are used in the treatment of LV systolic

dysfunction.


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o ACE inhibitors are used for preload and afterload reduction and prevention of

pulmonary or systemic congestion. They have been shown to decrease morbidity

and mortality rates in patients with heart failure due to systolic dysfunction. The

aim should be to use the target dose or the maximum tolerable doses. ACE

inhibitors are also indicated in patients with asymptomatic LV dilatation and

dysfunction.

o Beta-blockers (cardioselective or mixed alpha and beta), such as carvedilol,

metoprolol XL, and bisoprolol, have been shown to improve LV function and

decrease rates of mortality and morbidity from heart failure. Recent trials have

also shown improvement in outcomes for patients in NYHA class IV heart failurewith carvedilol administration. These drugs should be started when the patient has

no signs of fluid overload and is in compensated heart failure. Therapy should be

initiated with low doses, increasing the dose of the beta-blocker very slowly andclosely monitoring the patient for signs of worsening heart failure.

Low-dose spironolactone has been shown to decrease the rates of morbidity and mortality

in patients in NYHA class III or IV heart failure who are already taking ACE inhibitors.It is also recommended for use in post-MI patients with diabetes mellitus or a left

ventricular ejection fraction


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Specific diet recommendations include a diet low in sodium, high in potassium, rich in fresh

fruits and vegetables, low in cholesterol, and low in alcohol intake.

Sinha et al concluded that high intakes of red or processed meat were associated with modest

increases in total mortality, cancer mortality, and cardiovascular disease mortality. The baseline

population was a cohort of half a million people aged 50-71 years from the National Institutes ofHealth-AARP (formerly known as the American Association of Retired Persons) Diet and Health

Study.

Activity

Regular 30-minute sessions of aerobic exercise 3-4 times a week should be advised. Isometricand strenuous exercise should be avoided.

Follow-up

Further Inpatient Care

Daily weight and accurate fluid balance in patients with heart failure

Assessment of effectiveness and choice of antihypertensive treatment

Assessment of presence or absence of coronary artery disease and degree of LV systolic

function

Reinforcement of dietary advice

Reinforcement of advice regarding importance of regular exercise

Workup for secondary causes of hypertension if not already performed

Further Outpatient Care

Assessment of patient dietary habits and exercise pattern

Assessment of medication effectiveness

Assessment of adverse effects of various medications: Obtain urinalysis and BUN,

creatinine, and electrolyte levels to rule out renal insufficiency and electrolyte imbalances

secondary to medications and to quantitate proteinuria.

Assessment of patient compliance with medications

Screening for complications related to hypertension, such as cerebrovascular disease,hypertensive retinopathy, worsening heart failure, and renal failure

Surveillance for LVH by ECG or echocardiography

Assessment of effects of other medications: Advise the patient to avoid taking over-the-

counter medications, such as commonly used nonsteroidal anti-inflammatory drugs,

cough suppressants and decongestants containing sympathomimetics, which potentially

can raise BP.


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Deterrence/Prevention

Low-sodium diet

Fresh fruits and vegetable diet

Regular aerobic exercise

Avoidance of obesity

Patient Education

Patients should be educated regarding the following:

o Nature of the disease

o Risks associated with untreated hypertension

o Dietary advice

o Importance of regular exercise

o Importance of taking medications regularly

o Importance of weight loss

o Importance of avoiding medications and foods that can potentially elevate blood

pressure

.

Miscellaneous

Medicolegal Pitfalls

Failure to diagnose a correctible cause of hypertension

Failure to diagnose and adequately treat hypertension

Failure to recognize and aggressively treat LVH

Failure to provide adequate treatment for diastolic and systolic LV dysfunction

Failure to identify hypertension as a cause of heart failure

Failure to identify and treat other cardiovascular risk factors such ashypercholesterolemia, obesity, and coronary artery disease

Failure to provide adequate dietary advice

Special Concerns

LVH should be treated aggressively because patients with LVH represent the subgroup of

patients at the highest risk for cardiovascular events and mortality.


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Adequately control BP 24 h/d.

Identify and treat other coexisting risk factors for increased cardiovascular events, such

as hyperlipidemia, obesity, and coronary artery disease.

African Americans have a higher prevalence of and mortality rate from hypertensive

heart disease, and LVH in African Americans should be identified and treated moreaggressively than that in other groups.

Diet pills should be avoided.

8. Reference

Chobanian AV et al: The Seventh Report of the Joint National Committee on Prevention,

Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA

289:2560, 2003.

Kamran Riaz, Aqeel Ahmed, Hypertensive heart disease, 2009

Norman M. Kaplan. Kaplan's Clinical Hypertension 9th Edition, Lippincott Williams &

Wilkins, 2006

9. Modul tasks

1. Define the term hypertensive heart disease.2. Describe the pathophysiology of hypertensive heart disease.

3. What is the etiologi(es) of elevated blood pressure?

4. How to approach patient with hypertensive heart disease?

5. What are medications used to control elevated blood pressure?

6. Explain the consequencies of long-term elevated blood pressure to the heart.

7. Explain strategies to treat patient with hypertensive heart disease.8. Explain how to treat patient with left ventricular hypertrophy and left ventricular diastolic

and systolic dysfunctions.

Documents

Hypertensive Heart Disease-student