Michael A. Bauml, MD

Left ventricular hypertrophy (LVH) strongly predicts cardiovascular morbidity and overall mortality in hypertensive patients. ^1–7 Antihypertensive treatment that causes LVH to regress decreases the rates of adverse cardiovascular events and improves survival, independent of how much the blood pressure is lowered.^8–11 It is clinically important to recognize that LVH is a modifiable risk factor and that management is more complex than just blood pressure control.

This paper reviews the definition of LVH, compares the diagnostic tests for it, and discusses the current evidence-based approach to managing this dangerous risk factor.

A CHRONICALLY ELEVATED CARDIAC WORKLOAD CAUSES LVH

LVH is an abnormal increase in the mass of the left ventricular myocardium caused by a chronically increased workload on the heart.¹² This most commonly results from the heart pumping against an elevated afterload, as in hypertension and aortic stenosis. Another notable cause is increased filling of the left ventricle (ie, diastolic overload), which is the underlying mechanism for LVH in patients with aortic or mitral regurgitation and dilated cardiomyopathy. Coronary artery disease can also play a role in the pathogenesis of LVH, as the normal myocardium attempts to compensate for the ischemic or infarcted tissue.¹³

A key component in the development of LVH is myocardial fibrosis (Figure 1), which compromises cardiac function.¹⁴ The fibrosis is initially manifested by diastolic dysfunction, although systolic dysfunction also occurs with progressive disease.

The development of myocardial fibrosis appears to be pathophysiologically linked to the renin-angiotensin-aldosterone system. Specifically, there is evidence that angiotensin II has a profibrotic effect on the myocardium of hypertensive patients.¹⁵ This may explain why angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are among the most potent agents for treating LVH, as we will discuss later in this review.

Genetics also play an important role in the pathogenesis of LVH. Mutations in genes encoding sarcomeric proteins have a direct causal relationship in patients with hypertrophic cardiomyopathy.¹⁶ In addition, there appears to be a genetic predisposition that causes some patients with mild hypertension to develop LVH while others do not.^17,18

DIAGNOSIS BY ELECTROCARDIOGRAPHY, ECHOCARDIOGRAPHY, OR MRI

LVH can be detected by electrocardiography (Figure 2), echocardiography (Figure 3), or cardiac magnetic resonance imaging (MRI) (Figure 4). Each has unique advantages and disadvantages.

Electrocardiography is the cheapest and most readily available of the three tests for LVH. While its specificity is acceptably high, its clinical utility is limited by its very low sensitivity.^19,20

Many different criteria for electrocardiographic LVH have been proposed over the years. Most use the voltage in one or more leads, with or without additional factors such as QRS duration, secondary ST-T wave abnormalities, or left atrial abnormalities. The most well known electrocardiographic criteria are the Cornell voltage,²¹ the Cornell product,²² the Sokolow-Lyon index,²³ and the Romhilt-Estes point score system (Table 1).²⁴

A systematic review of 21 studies,¹⁹ published in 2007, found that all the criteria were less sensitive than specific:

• Cornell voltage—median sensitivity 15%, median specificity 96%
• Cornell product—median sensitivity 19.5%, median specificity 91%
• Sokolow-Lyon voltage—median sensitivity 21%, median specificity 89%
• Romhilt-Estes point score—median sensitivity 17%, median specificity 95%.

Of note, the ranges of the published values were extremely broad. For example, the ranges in sensitivity were:

• Cornell voltage—2% to 41%
• Cornell product—8% to 32%
• Sokolow-Lyon voltage—4% to 51%
• Romhilt-Estes point score—0% to 41%.

While the studies with the extreme values may have had issues of small sample size or poor study quality, the wide range in values may primarily be the result of diverse study populations as well as different validation methods and cutoff values to define LVH. Regardless, the overall message of high specificity and low sensitivity is indisputable.

Electrocardiography is insensitive for diagnosing LVH because it relies on measuring the electrical activity of the heart by electrodes on the surface of the skin to predict the left ventricular mass. The intracardiac electrical activity is problematic to measure externally because the measurements are affected by everything between the myocardium and the electrodes, most notably fat, fluid, and air. Because of this effect, electrocardiography underdiagnoses LVH in patients with obesity, pleural effusions, pericardial effusions, anasarca, or chronic obstructive pulmonary disease. In addition, the diagnosis of LVH by electrocardiography is strongly influenced by age and ethnicity.^25–26

While electrocardiography is not sensitive and cannot be used to rule out LVH, it still has a role in its diagnosis and management. In the landmark Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, regression of LVH (diagnosed electrocardiographically by the Sokolow-Lyon index or the Cornell product criteria) in response to losartan (Cozaar) improved cardiovascular outcomes independent of blood pressure.¹⁰ Based on this, it is reasonable that all hypertensive patients and other patients at risk of LVH who undergo electrocardiography be screened with these two criteria.

 

 

Echocardiography is the test of choice

Echocardiography, if available, should be the test of choice to assess for LVH. It is much more sensitive than electrocardiography and can also detect other abnormalities such as left ventricular dysfunction and valvular disease.

This test uses transthoracic or transesophageal ultrasonography to measure the left ventricular end-diastolic diameter, posterior wall thickness, and interventricular septum thickness. From these measurements and the patient’s height and weight, the left ventricular mass index can be calculated.²⁷

Several different cutoff values for the left ventricular mass index have been proposed; the LIFE study used values of > 104 g/m² in women and > 116 g/m² in men to define LVH.

When using echocardiography to assess for LVH, it is imperative that the left ventricular mass index be used and not just the left ventricular wall thickness, as often happens in clinical practice. This is necessary because diagnosis by wall thickness alone is not a good indicator of LVH, with a concordance between wall thickness and a left ventricular mass index of only 60%.²⁸ In addition, wall thickness tends to underestimate LVH in women and overestimate it in men.

Is echocardiography cost-effective?

Despite its clear advantages, an important consideration about echocardiography as a screening test for all hypertensive patients is its cost.

A suggested way to reduce cost is to measure the left ventricular mass index only.²⁹ A limited echocardiographic examination is much less expensive than a complete two-dimensional echocardiogram ($255 vs $431 per the 2009 Medicare Ambulatory Payment Classification³⁰) and should be the examination performed if the patient has no other clinical indication for echocardiography.

Another way to control cost is to stratify patients by risk and to do echocardiography only in those who would benefit most from it. Based on the prevalence of LVH, one study concluded that echocardiography is most cost-effective in men 50 years or older.³¹

Further study is necessary to more precisely define the cost-effectiveness of echocardiographic screening for LVH in terms of potentially preventable cardiovascular morbidity and death.

Cardiac MRI: The costly gold standard

Cardiac MRI is the gold standard test for LVH, as it is even more accurate and reproducible than echocardiography.³² It can precisely estimate a patient's left ventricular mass and assess for other structural cardiac abnormalities.

MRI’s use, however, is severely restricted in clinical practice due to its high cost and limited availability. While it may never be used for general screening for LVH, it certainly has a role in clinical research and for assessing cardiac anatomy in special clinical situations.

TREATMENT SHOULD INCLUDE AN ACE INHIBITOR OR ARB

Once LVH has been diagnosed, the next step is to decide on an appropriate treatment plan.

While the choice of therapy will always depend on other comorbidities, a 2003 metaanalysis of antihypertensive medications in the treatment of LVH (controlling for the degree of blood pressure lowering) showed that ARBs were the most efficacious class of agents for reducing the left ventricular mass.³³ Specifically, ARBs decreased the mass by 13%, followed by calcium-channel blockers at 11%, ACE inhibitors at 10%, diuretics at 8%, and beta-blockers at 6%. In pairwise comparison, ARBs, calcium-channel blockers, and ACE inhibitors were all significantly more effective in reducing the left ventricular mass than beta-blockers.

As previously discussed, LVH appears to be pathophysiologically linked to myocardial fibrosis and the renin-angiotensin-aldosterone system. For this reason and based on the data presented above regarding the degree of LVH regression, ACE inhibitors or ARBs should be used as the first-line agents for LVH unless they are contraindicated in the individual patient.

The LIFE study

The LIFE study offers the strongest evidence that treating LVH is beneficial. It showed that in hypertensive patients with electrocardiographic LVH by the Cornell product or Sokolow-Lyon criteria, treatment with antihypertensive drugs that resulted in less-severe LVH on electrocardiography was associated with lower rates of cardiovascular morbidity and death, independent of the blood pressure achieved or the drug used.¹⁰

The end point in this study was a composite of stroke, myocardial infarction, and cardiovascular death. Regression of electrocardiographic LVH in hypertensive patients has also been shown to decrease the incidence of diabetes mellitus,³⁴ atrial fibrillation,³⁵ and hospitalizations for heart failure.³⁶

The LIFE study also examined the prognostic implications of treating LVH detected by echocardiography. In this prospective cohort substudy, patients who had a lower left ventricular mass index during treatment with antihypertensive drugs had lower rates of cardiovascular morbidity and all-cause mortality, independent of the effects of blood pressure and treatment used.¹¹

These results suggest that there may be a role not only for treating LVH, but also for monitoring for a reduction in the left ventricular mass index as a goal of therapy (similar to the way hemoglobin A_1c is used in diabetic patients). If the index is used in this way, one could potentially adjust the dose of current drugs, switch classes, or add an additional drug based on a persistently elevated left ventricular mass index in order to optimize the patient's overall cardiovascular risk. A randomized controlled trial of therapy directed by the mass index vs conventional therapy of LVH would be necessary to assess the clinical utility of this approach.

RECOMMENDATIONS

LVH is a common and potentially modifiable cardiovascular risk factor often overlooked in clinical practice. Ideally, all hypertensive patients should be screened with echocardiography to look for LVH, using the calculated left ventricular mass index rather than wall thickness alone to make the diagnosis. While electrocardiography is specific and also has prognostic implications, it is not sensitive enough to be used alone to screen for LVH.

Once the diagnosis of LVH is made, the initial therapy should be an ARB or an ACE inhibitor. Response to therapy can be assessed by monitoring for a reduction in left ventricular mass index or regression of electrocardiographic LVH.

Treatment-induced regression of LVH decreases adverse cardiovascular events and improves overall survival. When modifying medications in hypertensive patients, it is important to remember that the treatment of LVH is not synonymous with blood pressure control.

Left ventricular hypertrophy (LVH) strongly predicts cardiovascular morbidity and overall mortality in hypertensive patients. ^1–7 Antihypertensive treatment that causes LVH to regress decreases the rates of adverse cardiovascular events and improves survival, independent of how much the blood pressure is lowered.^8–11 It is clinically important to recognize that LVH is a modifiable risk factor and that management is more complex than just blood pressure control.

This paper reviews the definition of LVH, compares the diagnostic tests for it, and discusses the current evidence-based approach to managing this dangerous risk factor.

A CHRONICALLY ELEVATED CARDIAC WORKLOAD CAUSES LVH

LVH is an abnormal increase in the mass of the left ventricular myocardium caused by a chronically increased workload on the heart.¹² This most commonly results from the heart pumping against an elevated afterload, as in hypertension and aortic stenosis. Another notable cause is increased filling of the left ventricle (ie, diastolic overload), which is the underlying mechanism for LVH in patients with aortic or mitral regurgitation and dilated cardiomyopathy. Coronary artery disease can also play a role in the pathogenesis of LVH, as the normal myocardium attempts to compensate for the ischemic or infarcted tissue.¹³

A key component in the development of LVH is myocardial fibrosis (Figure 1), which compromises cardiac function.¹⁴ The fibrosis is initially manifested by diastolic dysfunction, although systolic dysfunction also occurs with progressive disease.

The development of myocardial fibrosis appears to be pathophysiologically linked to the renin-angiotensin-aldosterone system. Specifically, there is evidence that angiotensin II has a profibrotic effect on the myocardium of hypertensive patients.¹⁵ This may explain why angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are among the most potent agents for treating LVH, as we will discuss later in this review.

Genetics also play an important role in the pathogenesis of LVH. Mutations in genes encoding sarcomeric proteins have a direct causal relationship in patients with hypertrophic cardiomyopathy.¹⁶ In addition, there appears to be a genetic predisposition that causes some patients with mild hypertension to develop LVH while others do not.^17,18

DIAGNOSIS BY ELECTROCARDIOGRAPHY, ECHOCARDIOGRAPHY, OR MRI

LVH can be detected by electrocardiography (Figure 2), echocardiography (Figure 3), or cardiac magnetic resonance imaging (MRI) (Figure 4). Each has unique advantages and disadvantages.

Electrocardiography is the cheapest and most readily available of the three tests for LVH. While its specificity is acceptably high, its clinical utility is limited by its very low sensitivity.^19,20

Many different criteria for electrocardiographic LVH have been proposed over the years. Most use the voltage in one or more leads, with or without additional factors such as QRS duration, secondary ST-T wave abnormalities, or left atrial abnormalities. The most well known electrocardiographic criteria are the Cornell voltage,²¹ the Cornell product,²² the Sokolow-Lyon index,²³ and the Romhilt-Estes point score system (Table 1).²⁴

A systematic review of 21 studies,¹⁹ published in 2007, found that all the criteria were less sensitive than specific:

• Cornell voltage—median sensitivity 15%, median specificity 96%
• Cornell product—median sensitivity 19.5%, median specificity 91%
• Sokolow-Lyon voltage—median sensitivity 21%, median specificity 89%
• Romhilt-Estes point score—median sensitivity 17%, median specificity 95%.

Of note, the ranges of the published values were extremely broad. For example, the ranges in sensitivity were:

• Cornell voltage—2% to 41%
• Cornell product—8% to 32%
• Sokolow-Lyon voltage—4% to 51%
• Romhilt-Estes point score—0% to 41%.

While the studies with the extreme values may have had issues of small sample size or poor study quality, the wide range in values may primarily be the result of diverse study populations as well as different validation methods and cutoff values to define LVH. Regardless, the overall message of high specificity and low sensitivity is indisputable.

Electrocardiography is insensitive for diagnosing LVH because it relies on measuring the electrical activity of the heart by electrodes on the surface of the skin to predict the left ventricular mass. The intracardiac electrical activity is problematic to measure externally because the measurements are affected by everything between the myocardium and the electrodes, most notably fat, fluid, and air. Because of this effect, electrocardiography underdiagnoses LVH in patients with obesity, pleural effusions, pericardial effusions, anasarca, or chronic obstructive pulmonary disease. In addition, the diagnosis of LVH by electrocardiography is strongly influenced by age and ethnicity.^25–26

While electrocardiography is not sensitive and cannot be used to rule out LVH, it still has a role in its diagnosis and management. In the landmark Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, regression of LVH (diagnosed electrocardiographically by the Sokolow-Lyon index or the Cornell product criteria) in response to losartan (Cozaar) improved cardiovascular outcomes independent of blood pressure.¹⁰ Based on this, it is reasonable that all hypertensive patients and other patients at risk of LVH who undergo electrocardiography be screened with these two criteria.

 

 

Echocardiography is the test of choice

Echocardiography, if available, should be the test of choice to assess for LVH. It is much more sensitive than electrocardiography and can also detect other abnormalities such as left ventricular dysfunction and valvular disease.

This test uses transthoracic or transesophageal ultrasonography to measure the left ventricular end-diastolic diameter, posterior wall thickness, and interventricular septum thickness. From these measurements and the patient’s height and weight, the left ventricular mass index can be calculated.²⁷

Several different cutoff values for the left ventricular mass index have been proposed; the LIFE study used values of > 104 g/m² in women and > 116 g/m² in men to define LVH.

When using echocardiography to assess for LVH, it is imperative that the left ventricular mass index be used and not just the left ventricular wall thickness, as often happens in clinical practice. This is necessary because diagnosis by wall thickness alone is not a good indicator of LVH, with a concordance between wall thickness and a left ventricular mass index of only 60%.²⁸ In addition, wall thickness tends to underestimate LVH in women and overestimate it in men.

Is echocardiography cost-effective?

Despite its clear advantages, an important consideration about echocardiography as a screening test for all hypertensive patients is its cost.

A suggested way to reduce cost is to measure the left ventricular mass index only.²⁹ A limited echocardiographic examination is much less expensive than a complete two-dimensional echocardiogram ($255 vs $431 per the 2009 Medicare Ambulatory Payment Classification³⁰) and should be the examination performed if the patient has no other clinical indication for echocardiography.

Another way to control cost is to stratify patients by risk and to do echocardiography only in those who would benefit most from it. Based on the prevalence of LVH, one study concluded that echocardiography is most cost-effective in men 50 years or older.³¹

Further study is necessary to more precisely define the cost-effectiveness of echocardiographic screening for LVH in terms of potentially preventable cardiovascular morbidity and death.

Cardiac MRI: The costly gold standard

Cardiac MRI is the gold standard test for LVH, as it is even more accurate and reproducible than echocardiography.³² It can precisely estimate a patient's left ventricular mass and assess for other structural cardiac abnormalities.

MRI’s use, however, is severely restricted in clinical practice due to its high cost and limited availability. While it may never be used for general screening for LVH, it certainly has a role in clinical research and for assessing cardiac anatomy in special clinical situations.

TREATMENT SHOULD INCLUDE AN ACE INHIBITOR OR ARB

Once LVH has been diagnosed, the next step is to decide on an appropriate treatment plan.

While the choice of therapy will always depend on other comorbidities, a 2003 metaanalysis of antihypertensive medications in the treatment of LVH (controlling for the degree of blood pressure lowering) showed that ARBs were the most efficacious class of agents for reducing the left ventricular mass.³³ Specifically, ARBs decreased the mass by 13%, followed by calcium-channel blockers at 11%, ACE inhibitors at 10%, diuretics at 8%, and beta-blockers at 6%. In pairwise comparison, ARBs, calcium-channel blockers, and ACE inhibitors were all significantly more effective in reducing the left ventricular mass than beta-blockers.

As previously discussed, LVH appears to be pathophysiologically linked to myocardial fibrosis and the renin-angiotensin-aldosterone system. For this reason and based on the data presented above regarding the degree of LVH regression, ACE inhibitors or ARBs should be used as the first-line agents for LVH unless they are contraindicated in the individual patient.

The LIFE study

The LIFE study offers the strongest evidence that treating LVH is beneficial. It showed that in hypertensive patients with electrocardiographic LVH by the Cornell product or Sokolow-Lyon criteria, treatment with antihypertensive drugs that resulted in less-severe LVH on electrocardiography was associated with lower rates of cardiovascular morbidity and death, independent of the blood pressure achieved or the drug used.¹⁰

The end point in this study was a composite of stroke, myocardial infarction, and cardiovascular death. Regression of electrocardiographic LVH in hypertensive patients has also been shown to decrease the incidence of diabetes mellitus,³⁴ atrial fibrillation,³⁵ and hospitalizations for heart failure.³⁶

The LIFE study also examined the prognostic implications of treating LVH detected by echocardiography. In this prospective cohort substudy, patients who had a lower left ventricular mass index during treatment with antihypertensive drugs had lower rates of cardiovascular morbidity and all-cause mortality, independent of the effects of blood pressure and treatment used.¹¹

These results suggest that there may be a role not only for treating LVH, but also for monitoring for a reduction in the left ventricular mass index as a goal of therapy (similar to the way hemoglobin A_1c is used in diabetic patients). If the index is used in this way, one could potentially adjust the dose of current drugs, switch classes, or add an additional drug based on a persistently elevated left ventricular mass index in order to optimize the patient's overall cardiovascular risk. A randomized controlled trial of therapy directed by the mass index vs conventional therapy of LVH would be necessary to assess the clinical utility of this approach.

RECOMMENDATIONS

LVH is a common and potentially modifiable cardiovascular risk factor often overlooked in clinical practice. Ideally, all hypertensive patients should be screened with echocardiography to look for LVH, using the calculated left ventricular mass index rather than wall thickness alone to make the diagnosis. While electrocardiography is specific and also has prognostic implications, it is not sensitive enough to be used alone to screen for LVH.

Once the diagnosis of LVH is made, the initial therapy should be an ARB or an ACE inhibitor. Response to therapy can be assessed by monitoring for a reduction in left ventricular mass index or regression of electrocardiographic LVH.

Treatment-induced regression of LVH decreases adverse cardiovascular events and improves overall survival. When modifying medications in hypertensive patients, it is important to remember that the treatment of LVH is not synonymous with blood pressure control.

Left ventricular hypertrophy (LVH) strongly predicts cardiovascular morbidity and overall mortality in hypertensive patients. ^1–7 Antihypertensive treatment that causes LVH to regress decreases the rates of adverse cardiovascular events and improves survival, independent of how much the blood pressure is lowered.^8–11 It is clinically important to recognize that LVH is a modifiable risk factor and that management is more complex than just blood pressure control.

This paper reviews the definition of LVH, compares the diagnostic tests for it, and discusses the current evidence-based approach to managing this dangerous risk factor.

A CHRONICALLY ELEVATED CARDIAC WORKLOAD CAUSES LVH

LVH is an abnormal increase in the mass of the left ventricular myocardium caused by a chronically increased workload on the heart.¹² This most commonly results from the heart pumping against an elevated afterload, as in hypertension and aortic stenosis. Another notable cause is increased filling of the left ventricle (ie, diastolic overload), which is the underlying mechanism for LVH in patients with aortic or mitral regurgitation and dilated cardiomyopathy. Coronary artery disease can also play a role in the pathogenesis of LVH, as the normal myocardium attempts to compensate for the ischemic or infarcted tissue.¹³

A key component in the development of LVH is myocardial fibrosis (Figure 1), which compromises cardiac function.¹⁴ The fibrosis is initially manifested by diastolic dysfunction, although systolic dysfunction also occurs with progressive disease.

The development of myocardial fibrosis appears to be pathophysiologically linked to the renin-angiotensin-aldosterone system. Specifically, there is evidence that angiotensin II has a profibrotic effect on the myocardium of hypertensive patients.¹⁵ This may explain why angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are among the most potent agents for treating LVH, as we will discuss later in this review.

Genetics also play an important role in the pathogenesis of LVH. Mutations in genes encoding sarcomeric proteins have a direct causal relationship in patients with hypertrophic cardiomyopathy.¹⁶ In addition, there appears to be a genetic predisposition that causes some patients with mild hypertension to develop LVH while others do not.^17,18

DIAGNOSIS BY ELECTROCARDIOGRAPHY, ECHOCARDIOGRAPHY, OR MRI

LVH can be detected by electrocardiography (Figure 2), echocardiography (Figure 3), or cardiac magnetic resonance imaging (MRI) (Figure 4). Each has unique advantages and disadvantages.

Electrocardiography is the cheapest and most readily available of the three tests for LVH. While its specificity is acceptably high, its clinical utility is limited by its very low sensitivity.^19,20

Many different criteria for electrocardiographic LVH have been proposed over the years. Most use the voltage in one or more leads, with or without additional factors such as QRS duration, secondary ST-T wave abnormalities, or left atrial abnormalities. The most well known electrocardiographic criteria are the Cornell voltage,²¹ the Cornell product,²² the Sokolow-Lyon index,²³ and the Romhilt-Estes point score system (Table 1).²⁴

A systematic review of 21 studies,¹⁹ published in 2007, found that all the criteria were less sensitive than specific:

• Cornell voltage—median sensitivity 15%, median specificity 96%
• Cornell product—median sensitivity 19.5%, median specificity 91%
• Sokolow-Lyon voltage—median sensitivity 21%, median specificity 89%
• Romhilt-Estes point score—median sensitivity 17%, median specificity 95%.

Of note, the ranges of the published values were extremely broad. For example, the ranges in sensitivity were:

• Cornell voltage—2% to 41%
• Cornell product—8% to 32%
• Sokolow-Lyon voltage—4% to 51%
• Romhilt-Estes point score—0% to 41%.

While the studies with the extreme values may have had issues of small sample size or poor study quality, the wide range in values may primarily be the result of diverse study populations as well as different validation methods and cutoff values to define LVH. Regardless, the overall message of high specificity and low sensitivity is indisputable.

Electrocardiography is insensitive for diagnosing LVH because it relies on measuring the electrical activity of the heart by electrodes on the surface of the skin to predict the left ventricular mass. The intracardiac electrical activity is problematic to measure externally because the measurements are affected by everything between the myocardium and the electrodes, most notably fat, fluid, and air. Because of this effect, electrocardiography underdiagnoses LVH in patients with obesity, pleural effusions, pericardial effusions, anasarca, or chronic obstructive pulmonary disease. In addition, the diagnosis of LVH by electrocardiography is strongly influenced by age and ethnicity.^25–26

While electrocardiography is not sensitive and cannot be used to rule out LVH, it still has a role in its diagnosis and management. In the landmark Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study, regression of LVH (diagnosed electrocardiographically by the Sokolow-Lyon index or the Cornell product criteria) in response to losartan (Cozaar) improved cardiovascular outcomes independent of blood pressure.¹⁰ Based on this, it is reasonable that all hypertensive patients and other patients at risk of LVH who undergo electrocardiography be screened with these two criteria.

 

 

Echocardiography is the test of choice

Echocardiography, if available, should be the test of choice to assess for LVH. It is much more sensitive than electrocardiography and can also detect other abnormalities such as left ventricular dysfunction and valvular disease.

This test uses transthoracic or transesophageal ultrasonography to measure the left ventricular end-diastolic diameter, posterior wall thickness, and interventricular septum thickness. From these measurements and the patient’s height and weight, the left ventricular mass index can be calculated.²⁷

Several different cutoff values for the left ventricular mass index have been proposed; the LIFE study used values of > 104 g/m² in women and > 116 g/m² in men to define LVH.

When using echocardiography to assess for LVH, it is imperative that the left ventricular mass index be used and not just the left ventricular wall thickness, as often happens in clinical practice. This is necessary because diagnosis by wall thickness alone is not a good indicator of LVH, with a concordance between wall thickness and a left ventricular mass index of only 60%.²⁸ In addition, wall thickness tends to underestimate LVH in women and overestimate it in men.

Is echocardiography cost-effective?

Despite its clear advantages, an important consideration about echocardiography as a screening test for all hypertensive patients is its cost.

A suggested way to reduce cost is to measure the left ventricular mass index only.²⁹ A limited echocardiographic examination is much less expensive than a complete two-dimensional echocardiogram ($255 vs $431 per the 2009 Medicare Ambulatory Payment Classification³⁰) and should be the examination performed if the patient has no other clinical indication for echocardiography.

Another way to control cost is to stratify patients by risk and to do echocardiography only in those who would benefit most from it. Based on the prevalence of LVH, one study concluded that echocardiography is most cost-effective in men 50 years or older.³¹

Further study is necessary to more precisely define the cost-effectiveness of echocardiographic screening for LVH in terms of potentially preventable cardiovascular morbidity and death.

Cardiac MRI: The costly gold standard

Cardiac MRI is the gold standard test for LVH, as it is even more accurate and reproducible than echocardiography.³² It can precisely estimate a patient's left ventricular mass and assess for other structural cardiac abnormalities.

MRI’s use, however, is severely restricted in clinical practice due to its high cost and limited availability. While it may never be used for general screening for LVH, it certainly has a role in clinical research and for assessing cardiac anatomy in special clinical situations.

TREATMENT SHOULD INCLUDE AN ACE INHIBITOR OR ARB

Once LVH has been diagnosed, the next step is to decide on an appropriate treatment plan.

While the choice of therapy will always depend on other comorbidities, a 2003 metaanalysis of antihypertensive medications in the treatment of LVH (controlling for the degree of blood pressure lowering) showed that ARBs were the most efficacious class of agents for reducing the left ventricular mass.³³ Specifically, ARBs decreased the mass by 13%, followed by calcium-channel blockers at 11%, ACE inhibitors at 10%, diuretics at 8%, and beta-blockers at 6%. In pairwise comparison, ARBs, calcium-channel blockers, and ACE inhibitors were all significantly more effective in reducing the left ventricular mass than beta-blockers.

As previously discussed, LVH appears to be pathophysiologically linked to myocardial fibrosis and the renin-angiotensin-aldosterone system. For this reason and based on the data presented above regarding the degree of LVH regression, ACE inhibitors or ARBs should be used as the first-line agents for LVH unless they are contraindicated in the individual patient.

The LIFE study

The LIFE study offers the strongest evidence that treating LVH is beneficial. It showed that in hypertensive patients with electrocardiographic LVH by the Cornell product or Sokolow-Lyon criteria, treatment with antihypertensive drugs that resulted in less-severe LVH on electrocardiography was associated with lower rates of cardiovascular morbidity and death, independent of the blood pressure achieved or the drug used.¹⁰

The end point in this study was a composite of stroke, myocardial infarction, and cardiovascular death. Regression of electrocardiographic LVH in hypertensive patients has also been shown to decrease the incidence of diabetes mellitus,³⁴ atrial fibrillation,³⁵ and hospitalizations for heart failure.³⁶

The LIFE study also examined the prognostic implications of treating LVH detected by echocardiography. In this prospective cohort substudy, patients who had a lower left ventricular mass index during treatment with antihypertensive drugs had lower rates of cardiovascular morbidity and all-cause mortality, independent of the effects of blood pressure and treatment used.¹¹

These results suggest that there may be a role not only for treating LVH, but also for monitoring for a reduction in the left ventricular mass index as a goal of therapy (similar to the way hemoglobin A_1c is used in diabetic patients). If the index is used in this way, one could potentially adjust the dose of current drugs, switch classes, or add an additional drug based on a persistently elevated left ventricular mass index in order to optimize the patient's overall cardiovascular risk. A randomized controlled trial of therapy directed by the mass index vs conventional therapy of LVH would be necessary to assess the clinical utility of this approach.

RECOMMENDATIONS

LVH is a common and potentially modifiable cardiovascular risk factor often overlooked in clinical practice. Ideally, all hypertensive patients should be screened with echocardiography to look for LVH, using the calculated left ventricular mass index rather than wall thickness alone to make the diagnosis. While electrocardiography is specific and also has prognostic implications, it is not sensitive enough to be used alone to screen for LVH.

Once the diagnosis of LVH is made, the initial therapy should be an ARB or an ACE inhibitor. Response to therapy can be assessed by monitoring for a reduction in left ventricular mass index or regression of electrocardiographic LVH.

Treatment-induced regression of LVH decreases adverse cardiovascular events and improves overall survival. When modifying medications in hypertensive patients, it is important to remember that the treatment of LVH is not synonymous with blood pressure control.