Left ventricular hypertrophy: An overlooked cardiovascular risk factor
ABSTRACTLeft ventricular hypertrophy (LVH) is common in hypertensive patients, and it increases the risk of myocardial infarction, stroke, and death. Recent evidence indicates it is a modifiable risk factor that is not entirely dependent on blood pressure control. The authors review its pathogenesis, diagnosis, and treatment.
KEY POINTS
- LVH is caused by a chronically increased cardiac workload, most commonly from hypertension.
- Ideally, all hypertensive patients should undergo echocardiography to screen for LVH, using the calculated left ventricular mass index.
- Electrocardiography is too insensitive to be used alone to screen for LVH.
- In hypertensive patients, initial therapy of LVH should consist of an angiotensin II receptor blocker or an angiotensin-converting enzyme inhibitor.
- Treatment-induced regression of LVH improves cardiovascular outcomes independent of blood pressure.
- Further study is necessary to examine the utility of following the left ventricular mass index as a treatment goal.
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 A1c 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.
