INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Uncontrolled and prolonged elevation of blood pressure (BP) can lead to a variety of changes in the myocardial structure, coronary vasculature, and conduction system of the heart. These changes 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, 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 various hemodynamic, structural, neuroendocrine, cellular, and molecular factors. On 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 in cardiac 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, especially in African Americans. The pathophysiologies of the various cardiac effects of hypertension differ and are described in this section.

Left ventricular hypertrophy

Of patients with hypertension, 15-20% develop LVH. The risk of LVH is increased 2-fold by associated obesity. The prevalence of LVH based on 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 a compensatory response to increased afterload. Mechanical and neurohormonal stimuli accompanying hypertension can lead to activation of myocardial cell growth, gene expression (Some of the genes are given expression primarily in fetal cardiomyocytes.), and, thus, 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. Thus, 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, concentric LVH, 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. Compare this with eccentric LVH, in which LV thickness is increased not uniformly but at certain sites, such as the septum. Concentric LVH is a marker of poor prognosis in the presence of hypertension. 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 very common 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 and LA 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. In addition 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. Some degree 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.

Heart failure

Heart failure is a common complication of chronically elevated BP. Hypertension as a cause of CHF 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 and without LVH may be as high as 33%. Chronically elevated afterload and resulting LVH can adversely affect both the active early relaxation phase and late compliance phase of ventricular diastole.

Diastolic dysfunction is common in persons with hypertension. It is usually, 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, systolic dysfunction, 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 dilate to 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-angiotensin systems, leading to increases in salt and water retention and increased peripheral vasoconstriction, 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 the asymptomatic 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 or dysfunction 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 as results of septal thickening and LV dysfunction.

Myocardial ischemia

Patients with angina have a high prevalence of hypertension. Hypertension is an established risk factor 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 coronary blood 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, is exacerbated in arteries subjected to chronically elevated BP. Shear stress associated with 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 the development 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 the pathogenesis 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 had hypertension. 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, more importantly, 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 these arrhythmias is thought to be concomitant coronary artery disease and myocardial fibrosis.

Frequency

United States

The exact frequency is unknown. The rate of LVH based on ECG findings is 2.9% for men and 1.5% for women. The rate of LVH based on echocardiography findings is 15-20%. Of patients without LVH, 33% have evidence of asymptomatic LV diastolic dysfunction. Hypertension accounts for 10% of cases of CHF and, in the elderly population, as many as 68%. Some 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 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 the type of LVH. Concentric LVH increases the risk of cardiovascular events the most, as much as 30% over a 10-year period in one study, compared with 15% with concentric remodeling and 9% without any 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 risk of 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 with LVH. 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-year cardiovascular 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 to hypertension, risk of all cause mortality and cardiovascular events is significantly increased. This risk increases with an increase in the pulmonary artery wedge pressure. LV diastolic dysfunction, and the heart failure symptoms associated with it, have been shown to improve with treatment aimed at lowering BP and reducing LVH. Whether such treatment 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 with NYHA 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 whites, as is death from hypertensive heart disease. 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 and because 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.

Sex

Systolic BP increases with age. This increase is more marked in men until women reach menopause, when BP rises more sharply in women and reaches levels higher than in men. The prevalence of hypertension is higher in men younger than 55 years but is higher in women older than 55 years. The prevalence of hypertensive heart disease probably follows 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

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 diagnosis of hypertension.

• 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
• • 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.
  • 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
  • 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 develop cardiac arrhythmias, especially atrial fibrillation, or they can develop symptoms of heart failure insidiously over time.
• Myocardial ischemia
• • Angina, a frequent complication of hypertensive heart disease, is also indistinguishable from other causes of myocardial ischemia.
  • Typical symptoms of angina include substernal chest pain lasting less than 20 minutes (versus >20 min in infarction). Pain is 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
  • Patients also may present with atypical symptoms without chest pain, such as exertional dyspnea, commonly referred to as an angina equivalent.
  • The patient may present with chronic stable angina or acute coronary syndrome, including myocardial infarction without ST-segment elevation and acute myocardial 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.
  • 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 transmural pressure 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 heart failure, 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 physical examination may be entirely normal in the very early stages of the disease, or the patient may have 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, and abdominal mass in polycystic kidney disease.

• Pulses: The arterial pulses are normal in the early stages of the disease.
• • Rhythm
    • Regular if the patient is in sinus rhythm
    • Irregularly irregular if the patient is in atrial fibrillation
  • Rate
    • Normal in patients in sinus rhythm and not in decompensated heart failure
    • Tachycardic in patients with heart failure and in patients with atrial fibrillation and a rapid ventricular response
  • Volume
    • Normal
    • Decreased in patients with LV dysfunction
  • Additional findings - May include radial-femoral delay if the etiology of hypertension 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 higher than 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 generate enough 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
• • 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 dysfunction supervenes, the apical impulse is displaced laterally, owing to LV dilatation.
  • Right ventricle: A lift is present late in the course of heart failure if significant pulmonary hypertension develops.
  • Heart sounds: S₁ is normal in intensity and character. S₂ at the right upper sternal border 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 overload and LVH. S₃ typically is not present initially but is audible in the presence of heart failure, either systolic or diastolic.
  • 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
• • CNS examination findings are usually unremarkable unless the patient has had previous cerebrovascular accidents with residual deficit.
  • 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.

Causes

The cause of hypertensive heart disease is chronically elevated BP. The causes of elevated BP are 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:
• • Renal causes
    • Renal artery stenosis
    • Polycystic kidney disease
    • Chronic renal failure
    • Intrarenal Vasculitis
  • Endocrine causes
    • Primary hyperaldosteronism
    • Pheochromocytoma
    • Cushing syndrome
    • Congenital adrenal hyperplasia
    • Hypothyroidism and hyperthyroidism
    • Acromegaly
    • Exogenous hormone (eg, corticosteroids, estrogens), sympathomimetics, monoamine oxidase inhibitors (MAOIs), and tyramine-containing foods
  • 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 secondary to a hyperdynamic circulation)

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Hypertrophic cardiomyopathy
Athlete's heart
CHF due to other etiologies
Atrial fibrillation due to other etiologies
Diastolic dysfunction due to other etiologies
Sleep apnea

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory studies are helpful in establishing the etiology of hypertension, quantitating severity of target organ damage, and monitoring the adverse effects of therapy.
• BUN and creatinine levels are elevated in patients with renal failure.
• 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 elevated in patients with primary hyperaldosteronism.
• Twenty-four–hour 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:
• • Notching of the undersurface of the ribs - Secondary to the development of collateral circulation in coarctation of the aorta
  • Cardiomegaly - Secondary to LV dilatation, in late stages of the disease
  • Cephalization of pulmonary blood flow, Kerley B lines, and alveolar infiltrates - In patients with elevated LV end-diastolic pressure and pulmonary congestion
  • Blunting of costophrenic angle - In patients who develop pleural effusion
• CT scanning, MRI, and magnetic resonance angiography of the abdomen and chest show the presence of adrenal masses or evidence of coarctation of aorta.
• CT scanning and MRI of the heart, although not used routinely, have been shown in experimental studies to quantify LVH.
• Transthoracic echocardiography (TTE) may be very useful in identifying features of hypertensive heart disease (see Media files 1-4).
• • Evidence of LVH
  • • TTE is more sensitive and specific then ECG for diagnosing the presence of LVH—57% for mild and 98% for severe LVH.
    • LVH is symmetrical, while the hypertrophy of hypertrophic cardiomyopathy is asymmetrical. Definition of the LVH based on echocardiography 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.
    • The Troy formula was used in the Framingham Heart study and is recommended by the American Society of Echocardiography. LV mass is calculated as follows, in which LVEDD is left ventricular end-diastolic diameter, IVS is interventricular septal thickness, and PW is posterior wall thickness:

      LV mass = 1.05[(LVEDD + IVS + PW)3 - LVEDD3]

      In various studies, LVH has been defined either as LV mass greater than 215 g or greater than 225 g. Because LV mass is affected by height, weight, and body surface area, LVMI, defined as LV mass divided by body surface area, more accurately sets the limits for LV mass. Framingham Heart Study data indicate that abnormal LVMI limits are 134 g/m² for men and 110 g/m² for women.

  • 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 to the impaired compliance phase.
    • The tissue Doppler indices are abnormal. The tissue Doppler profile shows a reversed E:A ratio. This is especially helpful in patients who have a pseudonormal pattern on transmitral flow velocity Doppler studies.
  • 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.
  • Evidence of LA dilatation
  • Evidence of right-sided dilatation: Right-sided chambers may be dilated with some degree of pulmonary hypertension.
  • 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
• Other tests may be ordered for excluding other secondary causes of hypertension.
• Twelve-lead ECG may show a variety of abnormalities.
• • Evidence of left atrial enlargement - Broad P waves in limb leads and prominent and wide delayed negative deflection in V₁ (see Media files 5-6)
  • 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.
  • Evidence of LVH on ECG
  • • The frequency of LVH on ECG at the time of initial diagnosis varies from 10-100%; in a recent trial, the frequency was 13%.
    • The sensitivity of ECG for diagnosing LVH is limited, 30-57% in patients with severe LVH.
  • Other criteria: Various criteria, differing in sensitivity and specificity, have been used to diagnose LVH, as summarized below. Note that the specificities and sensitivities of all these approaches are far less than those of echocardiography.
  • • The Cornell criteria (most sensitive) are (1) RaVL plus an S wave in V₃ of greater 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 as 50-60%. 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 2.6 mV. 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.
    • Table 1. Romhilt-Estes Criteria (a point score system*)

      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

    *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 the severity of elevated pulmonary artery pressure in patients with heart failure.

Histologic Findings

Gross findings

LVH (concentric) occurs without dilatation of the LV (see Media file 7). The ratio of wall thickness to the radius of 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.

Microscopic findings

The earliest changes of hypertensive heart disease include myocyte enlargement, with an increase in their transverse diameters (see Media file 8). At a more advanced stage, cellular and nuclear enlargement (with variation in cell size), loss of myofibrils, and interstitial fibrosis occur (see Media files 9-10).

Staging

BP and hypertension itself have been divided into stages.

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

When the BP is more than 20/10 mm Hg above the goal, consideration should be given to initiating 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.
• 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

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

The medical care of patients with hypertensive heart disease falls under 2 categories—treatment of the elevated BP and prevention and treatment of hypertensive heart disease. The BP goal should be less than 140/90 mm Hg in patients without diabetes or chronic kidney disease and less than 130/90 mm Hg in those with either of these diseases. 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 artery disease, 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 the symptoms 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.
  • A 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 hypertension—mainly African Americans—with low renin levels. Restriction of sodium in these patients does not lead to compensatory stimulation of the renin-angiotensin system and thus has a potent antihypertensive effect. Recent data indicates that sodium reduction, previously shown to lower blood 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 to an average 2-8 mm of Hg reduction in BP.
  • In 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. Foods rich in potassium, such as fresh fruit and vegetables, should be recommended for patients with normal renal function.
  • A diet rich in fresh fruits and vegetables, known as the 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. This diet should be advised in patients with hypertension.
  • A low-cholesterol diet is part of secondary prophylaxis in patients with coronary artery disease. It is also a part of the primary prophylaxis of coronary artery disease in patients at high risk for this disease.
  • Heavy 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
• • Regular dynamic isotonic exercise, such as walking, running, swimming, or cycling, has been shown to decrease BP and improve cardiovascular well-being. Regular isotonic exercise 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.
  • Regular 30-minute sessions of aerobic exercise 3-4 times a week should be advised. Average reduction in BP with regular aerobic exercise such as walking at least 30 minutes most days of the week is 4-9 mm of Hg. Isometric and strenuous exercise should be avoided.
• Weight reduction
• • Obesity has been linked to hypertension and LVH in various epidemiological studies, with as many as 50% of obese patients having some degree of hypertension and as many as 60-70% of patients with hypertension being obese. Abdominal adiposity, clinically measured as waist-to-hip ratio and more accurately assessed by abdominal CT scan, is a more sensitive risk factor for hypertension. 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.
  • 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.
• 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 combined alpha- and beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, and direct vasodilators such as hydralazine. 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.
  • Thiazide diuretics are the drugs of first choice in most patients with uncomplicated hypertension, as outlined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
  • Drugs from other classes can be used in the presence of compelling indications.
  • • Calcium channel blockers are effective for systolic hypertension in elderly patients.
    • ACE inhibitors are the first choice in patients with diabetes and/or LV 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 due to systolic LV dysfunction, patients with ischemic heart disease with or without a history of myocardial infarction, and in patients with thyrotoxicosis.
    • Peripheral alpha-channel blockers should be avoided in patients with hypertension in view of recent findings of their adverse effect on cardiovascular morbidity and mortality rates.
    • Central alpha-antagonists have no evidence-based support and have more adverse effects.
  • Intravenous drugs used in patients with a hypertensive emergency include nitroprusside, labetalol, hydralazine, enalapril, and beta-blockers (avoided in patients with acutely decompensated heart failure).
  • Some evidence shows that peroxisome proliferator-activated receptor gamma (PPARγ) agonist ameliorates oxidative stress and leads to reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium and LVH.
  • Once a day medications have shown to improve patient compliance.
• Treatment of LVH
• • 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 electrocardiographic LVH is associated with less hospitalization for heart failure in hypertensive patients.
  • 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
• • Certain classes of antihypertensives—ACE inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers—have been shown (although not consistently) to improve echocardiographic parameters in symptomatic and asymptomatic diastolic dysfunction and the symptomatology of heart failure.
  • Use diuretics and nitrates with caution in patients with heart failure due to diastolic dysfunction. These drugs may cause severe hypotension by inappropriately decreasing the preload, which is required for adequate LV filling pressures. If diuretics are indicated, delicate titration is necessary.
  • Hydralazine has been shown to cause severe hypotension in patients with heart failure due to diastolic dysfunction.
  • 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
• • Diuretics (predominantly loop diuretics) are used in the treatment of LV systolic dysfunction.
  • 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.
  • 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 failure with 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 and closely 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.
• Treatment of cardiac arrhythmias
• • Treatment depends upon the specific arrhythmia and the underlying LV function.
  • Anticoagulation should be considered in patients with atrial fibrillation.
• Treatment of anxiety, stress, sleep apnea, and other contributing or precipitating factors

Surgical Care

Surgical treatment may be necessary for definitive treatment in selected cases of secondary causes for hypertension.

Consultations

• Hypertension specialist
• Heart failure specialist
• Heart failure nurse
• Electrophysiologist for treatment of complex arrhythmias
• Sleep specialist (if sleep apnea is suspected)

Diet

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. See Dietary modifications for more information.

Activity

Regular 30-minute sessions of aerobic exercise 3-4 times a week should be advised. Isometric and strenuous exercise should be avoided. See Regular aerobic exercise for more information.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Thiazides and related diuretics

Studies have shown that these agents reduce LVH.

Drug Category: Alpha/beta-adrenergic blocking agents

Beta-adrenergic blockers inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation. At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of alpha-receptor blockers.

Drug Category: Beta-adrenergic blocking agents

Cardioselective and noncardioselective agents are used to treat hypertension. In addition, they can be used in treatment of arrhythmias (eg, ventricular ectopy) and for rate control in atrial fibrillation. They are also an important part of therapy for heart failure due to systolic or diastolic LV dysfunction. Whether they have any special influence in treatment of heart failure due to hypertension is not clear.

Drug Category: Angiotensin-converting enzyme inhibitors

Have been shown to decrease morbidity and mortality rates in patients with heart failure. ACE inhibitors lower elevated BP and decrease afterload with a favorable influence on remodeling; they also have been shown to reduce LVH at doses not known to decrease BP. Studies have shown improved outcomes in patients with diabetes, proteinuria, and/or renal failure, especially when compared with dihydropyridine calcium channel blockers.

Drug Category: Angiotensin II receptor antagonists

Can be used in patients intolerant of ACE inhibitors. Have been shown effective in hypertension and heart failure. Early data suggest they also reverse LVH, and recent trial data support their renal protective effect. Angiotensin II receptor antagonists include losartan (Cozaar), valsartan (Diovan), candesartan (Atacand), irbesartan (Avapro), eprosartan (Teveten), and olmesartan (Benicar).