Left Ventricular Hypertrophy and Diastolic Dysfunction
Our understanding of systemic hypertension and its vascular complications has been expanding steadily in the past two decades. This progress has refined methods for the measurement of hypertensive disease complications and allowed an inquiry into the clinical factors that may accelerate them. The heart is a prime target for hypertensive damage, suffering accelerated coronary atherosclerosis, left ventricular hypertrophy, arrhythmias, and congestive heart failure .
Left ventricular hypertrophy is initially a compensatory mechanism for the increased systemic vascular resistance that occurs in hypertension, but this hypertrophy eventually becomes deleterious and can result in inadequate myocardial perfusion and cardiac dysfunction. Left ventricular hypertrophy has emerged as an independent cardiovascular risk factor with prognostic precision that may be better than blood pressure itself. Primary care physicians must therefore be aware of the importance of Left ventricular hypertrophy as a cardiovascular risk factor, understand the methods of detecting Left ventricular hypertrophy and diastolic dysfunction, and be aware of current methods of treating Left ventricular hypertrophy.
Epidemiology of hypertensive cardiac hypertrophy
Blood pressure is the major determinant of left ventricular mass index (left ventricular mass corrected for body surface area) with better correlation with 24-h ambulatory blood pressure measurement than office blood pressure. This is probably because of the greater reproducibility of ambulatory blood pressure compared with office blood pressure and the fact that it more closely represents overall blood pressure levels. Similar to other hypertensive complications, systolic (both basal and exercise blood pressure) rather than diastolic blood pressure is more consistently related to left ventricular mass index. The prevalence of Left ventricular hypertrophy among hypertensive subjects varies from 3 to 50%, depending on whether electrocardiography or echocardiography is used for diagnosis and whether treated or untreated patients are studied. This variability not only reflects differences in the populations studied, the severity of hypertension, but the methods and normal values used to define Left ventricular hypertrophy. It is apparent that Left ventricular hypertrophy is a common finding in hypertensive subjects.
Although the overall hemodynamic load is certainly the prime element in the development of Left ventricular hypertrophy, several other clinical factors affect the clinical expression of left ventricular mass. Epidemiologic studies such as The Framingham Study have shown that the prevalence of Left ventricular hypertrophy increases slowly with age with a sharp rise in subjects over 60 yr. However, this increase in Left ventricular hypertrophy with age may be dependent on other factors such as the prevalence of hypertension or obesity. It has also been revealed that women have less Left ventricular hypertrophy than similarly aged men until about the sixth decade, after which the rates are higher in women. The effects of body mass index on cardiac mass are noteworthy because for any given level of blood pressure the prevalence of Left ventricular hypertrophy increases sharply as body mass index increases. Thus, it is appropriate to express left ventricular mass indexed for body surface area, body weight, or height. Many other clinical and pathophysiologic factors have been suggested to play a role in the development of Left ventricular hypertrophy.
Table Clinical and Pathophysiologic Factors Linked to Increase in Left Ventricular Mass
| Clinical Factors | Pathophysiologic Factors |
| Blood pressure | Glucose intolerance |
| Age | Sympathetic nervous system activity |
| body mass index | Renin-angiotensin system activity |
| Alcohol intake | Insulin and growth hormone |
| Sodium intake | |
| Race and family history | |
| Valvular heart disease | |
| Uremia |
One contentious issue is whether race is itself an independent factor in the higher prevalence of Left ventricular hypertrophy in African Americans. This remains an unresolved but debated area.
Pathophysiology of left ventricular hypertrophy
Current thinking about the pathogenesis of Left ventricular hypertrophy is that of an adaptive process initially. It is thought to be initiated by sustained or episodic increases in blood pressure that impart added work on the heart with increases in wall stress (Laplace’s law) and myocardial oxygen consumption. This then leads, through several cellular mechanisms, to hypertrophy of myocytes as well as other supporting tissue. Note that cardiac myocytes cannot undergo hyperplasia because adult myocytes are terminally differentiated and cannot replicate. Because there is inadequate capillary increase to keep up with the cardiac hypertrophy, the relative capillary density is reduced with a possibility for inadequate coronary flow to meet the demands of the bigger myocardium. The increase in cardiac mass is associated with an increase in left ventricular end-diastolic pressure, which may eventually lead to reductions in filling for the ventricle. Furthermore, the hypertensive heart becomes more dependent on left atrial emptying to maintain cardiac output. In extreme forms of diastolic dysfunction with abnormalities of left atrial function, clinical congestive heart failure may develop.
T= PR/2
where T= wall tension, P= pressure, R = radius of chamber. Increases in pressure must cause increases in tension. But
S= T+h
S = wall stress, t = wall tension, h = average wall thickness.
Therefore
P= (S- h- 2) + Я
Therefore any increase in wall stress must be accompanied by increases in h/R, which is the relative wall thickness. The typical change in the heart is an increase in both septal and posterior wall thickness giving concentric left ventricular hypertrophy.
Adverse consequences of left ventricular hypertrophy
Several large epidemiologic and prospective studies have shown that electrocardiography or echocardiographic Left ventricular hypertrophy is a serious finding and increases the risk for coronary artery disease, congestive heart failure, stroke, cardiac arrhythmias, and sudden death. Subjects with Left ventricular hypertrophy suffer about two to four times the cardiac complications of hypertension as their hypertensive counterparts with no Left ventricular hypertrophy. Furthermore, these findings have been reported in a variety of patient populations: subjects with and without hypertension and with and without coronary artery disease. In one report from The Framingham Study, the cardiovascular mortality in a group of subjects with electrocardiography-determined Left ventricular hypertrophy with ST-T wave changes was about seven times higher than that of an age-matched group with normal electrocardiography. Other work has shown that patients with Left ventricular hypertrophy who experience a myocardial infarction (myocardial infarction) have a higher death rate than similar subjects without Left ventricular hypertrophy with an acute myocardial infarction. Further data published from The Framingham Study on a group of 3220 subjects over age 40 and who were clinically free of cardiovascular disease show that echocardiographic determination of left ventricular mass was associated positively with the incidence of cardiovascular disease and death from cardiovascular disease. Similar results have been obtained on a group of elderly patients from the same database. Therefore, Left ventricular hypertrophy is a cardiovascular risk factor similar in importance to diabetes, hypertension, and hypercholesterolemia. In fact, the Sixth Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) has included Left ventricular hypertrophy as one of the factors in stratifying patients into the high-risk category.
From a practical point of view, the finding of Left ventricular hypertrophy on electrocardiography with ST-T wave abnormalities should be as ominous to the primary care physician as the finding of old q-waves indicative of a previous myocardial infarction. Similarly, an echocardiographic report of Left ventricular hypertrophy based on an increase in relative wall thickness and normal chamber size should also alert the clinician that the subject is at increased risk.
Left ventricular mass, hypertension, and diastolic dysfunction
Diastolic dysfunction may be seen in patients with enlargement of the heart (either Left ventricular hypertrophy or hypertrophic cardiomyopathy), with infiltrative disease, or with coronary artery disease. The type of diastolic dysfunction of interest here is that found in many hypertensive patients with and without electrocardiography-Left ventricular hypertrophy. As the extent of Left ventricular hypertrophy increases, so does the incidence of diastolic dysfunction. With time, the impaired relaxation of the ventricle during left ventricular filling is severe enough to produce symptoms during exertion or during atrial fibrillation. Lhe fact that many patients with Left ventricular hypertrophy will become symptomatic during atrial fibrillation is explained by the increased contribution of atrial contraction to left ventricular filling in these subjects. Loss of the atrial contribution to left ventricular filling during atrial fibrillation precipitates symptoms owing to increased pulmonary wedge pressure. Note that diastolic dysfunction may also be accompanied by systolic dysfunction and a reduced left ventricular ejection fraction. However, systolic function is typically preserved in most hypertensive subjects without coronary artery disease and diastolic perturbations predominate.
Detection of Left ventricular hypertrophy and diastolic dysfunction
Left ventricular hypertrophy can be detected noninvasively using 12-lead electrocardiographyas well as echocardiography. Electrocardiography is still recommended in the routine evaluation of hypertensive subjects whereas echocardiography should be reserved for selected patients. Electrocardiographic detection of Left ventricular hypertrophy has lower sensitivity than echocardiography but has strong risk prediction when ST-T wave abnormalities are also present. It has been suggested that these ST-T wave changes may be indicative of myocardial ischemia — hence the high risk for coronary events in this group of patients.
Echocardiographic detection of Left ventricular hypertrophy can be done using both M-mode and 2-D echocardiography; it is well established and gives information about anatomical hypertrophy. A limited M-mode study can provide the wall thickness and left ventricular diastolic dimensions to calculate left ventricular mass. The data obtained from echocardiography also allow the separation of the types of Left ventricular hypertrophy into concentric, eccentric, and concentric remodeling. Currently, however, whether such an analysis provides major additional prognostic significance beyond left ventricular mass is not clear. More detailed examination with Doppler technology can provide objective measures of left ventricular filling. Many of the noninvasive indices used are not specific for hypertensive diastolic dysfunction and may be seen in diastolic dysfunction secondary to coronary artery disease and various metabolic or infiltrative diseases.
The most common index used to infer diastolic dysfunction is an alteration in the E:A wave velocity ratio of left ventricular filling. The E wave represents the early active filling phase in diastole and the A wave represents atrial filling. The normal ratio varies with age but is usually >1.0, and in general a ratio <0.5 is clearly abnormal. Other Doppler changes seen in situations of impaired relaxation include prolonged deceleration time and an increased isovolumetric relaxation time. In the hypertrophied ventricle, a low E wave is seen with a tall
A wave indicative of reduced early filling and late filling promoted by enhanced left atrial contraction. The primary care physician may be told that there has been a reduction in the E:A ratio. These patterns are also affected by age, and preload and considerable care is necessary in interpretation.
These Doppler-based abnormalities of flow are common. Even in relatively young untreated subjects with mild hypertension and without Left ventricular hypertrophy, electrocardiography shows that about 20-25% have abnormal left ventricular filling. The abnormalities of diastolic function may antedate overt Left ventricular hypertrophy.
Regression of left ventricular hypertrophy and outcome
It makes intuitive sense that therapy to reverse Left ventricular hypertrophy should reduce cardiovascular risk in these patients. Diastolic dysfunction improves appreciably when Left ventricular hypertrophy is reversed by antihypertensive therapy, and such improvement may be seen in a few months. Furthermore, reversal of Left ventricular hypertrophy should translate into a reduction in cardiovascular risk. Several studies now indicate that this may indeed be true. In the most recent of these studies, 430 patients with essential hypertension were followed for an average of 2.8 yr. All patients were studied with electrocardiography and ambulatory blood pressure monitoring and cardiovascular events ascertained over time. The group of patients in whom there was an increase of left ventricular mass during follow-up had a higher rate of cardiovascular events than the group in whom there was a decrease in left ventricular mass. Furthermore, in the subgroup with Left ventricular hypertrophy at commencement of the study, there was a higher event rate among those whose left ventricular mass increased during therapy compared with those in whom left ventricular mass decreased with follow-up. It therefore appears that a reduction in left ventricular mass predicts a lower risk than in those patients whose left ventricular mass increases over time. A large multicenter trial, Losartan Intervention for Endpoints, with hard cardiovascular end points is nearing completion and is comparing the angiotensin II receptor blocker losartan to atenolol in patients with established electrocardiography-Left ventricular hypertrophy.
A controversial issue remains whether certain antihypertensive agents are superior in reducing left ventricular mass and therefore reducing risk. Current data do not support one class of antihypertensive agent over others except that vasodilators that induce reflex tachycardia are to be avoided as monotherapy. Our practice is to reduce elevated blood pressure by whatever methods possible, including lifestyle modifications. If there is an unusually large left ventricular mass for a patient with stage 1 to 2 hypertension, then some consideration should be given to performing ambulatory blood pressure monitoring to document sleep blood pressure, which may exaggerate Left ventricular hypertrophy if elevated. Additional recommendations should include reduction of salt and alcohol intake and attainment of ideal body weight if possible. The antihypertensive drugs of choice for these subjects should be guided by compelling indications and concomitant diseases as outlined in the JNC VI report.
Role of left ventricular hypertrophy and diastolic dysfunction in heart failure
The presence of diastolic dysfunction as a contributing factor to congestive heart failure is significant. The clinical features of both systolic and diastolic forms of heart failure are similar, making routine noninvasive evaluation of ventricular function during the episode mandatory in these patients. Echocardiography not only detects diastolic dysfunction but also excludes coexisting valvular, pericardial, and restrictive disease. In many patients with preserved systolic function but clinical evidence for heart failure, ischemia may be playing a role and should be actively excluded. In as many as one third of subjects with clinical heart failure, diastolic dysfunction is the cause or major contributor to their disease process. Although subjects with diastolic heart failure have lower mortality rates than their counterparts with systolic failure, the morbidity and mortality is still substantial. Also of interest is the finding that the incidence of congestive heart failure with isolated diastolic dysfunction as the cause increases impressively with age.
The best therapies for subjects with hypertensive diastolic heart failure are not known. Empiric suggestions derived from clinical experience include careful diuretic use to eliminate congestive symptoms, maintenance of sinus rhythm, and use of antihypertensive agents that slow heart rate and increase filling time. The use of digoxin should be limited to patients with atrial fibrillation. The goal blood pressure in these subjects remains unclear although office blood pressure of 135/85 mmHg may be a reasonable goal. Serial echocardiographic measures of left ventricular mass, though of limited reproducibility, may be useful to confirm regression of Left ventricular hypertrophy.
Conclusion
Unfortunately, too many hypertensive patients develop Left ventricular hypertrophy. The presence of Left ventricular hypertrophy among hypertensive patients should be treated with concern because it is not a mere cardiac manifestation of hypertension but portends a worsened clinical outcome. Ideally, prevention of Left ventricular hypertrophy should be the goal by maintaining good blood pressure control, ideal body weight, and reduced salt intake. Left ventricular hypertrophy is accompanied initially by minor echo-cardiographic abnormalities of diastolic function, but as time progresses these worsen and can induce heart failure. There is promising evidence that antihypertensive therapy to reduce left ventricular mass is beneficial. Suggested therapy for isolated diastolic heart failure associated with Left ventricular hypertrophy includes maintenance of sinus rhythm and control of heart rate, relief of pulmonary congestion, and good blood pressure control in the long term. Hypertensive heart disease, once identified, remains a major challenge to treat.
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