**3. Echocardiography**

Hypertension is one of the most important risk factors for heart failure with increasing risk in all age groups. The lifetime risk for developing heart failure is doubled for subjects with blood pressure > 160/100mm Hg compared to those with blood pressure < 140/90 mm Hg [8]. Systolic and diastolic heart failure are both associated with hypertension. There are several mecha‐ nisms, alone or in combination, leading to development of heart failure in the presence of hypertension: left ventricular hypertrophy (LVH), chamber remodeling, hemodynamic load and coronary microvascular disease with impaired coronary hemodynamics. To assess subclinical organ damage, such as ventricular hypertrophy, echocardiography is more sensitive than electrocardiography [9], which is a routine examination in all subjects with high blood pressure. However, the ESC/ESH guidelines suggest that in patients with low and intermediate cardiovascular risk an echocardiography should be performed for better global cardiovascular risk stratification which may implicate the appropriate pharmacological treatment [10]. The role of echocardiography is not limited to identification of (sub-) clinical organ damage in the pre-treatment phase. Since changes of the left ventricular hypertrophy in response to treatment are associated to cardiovascular fatal and non-fatal events [11], echo‐ cardiography can also be used to monitor treatment's success and re-assess overall risk.

Left ventricular hypertrophy is the first step toward the development of hypertensive heart disease. The echocardiographic evaluation of LVH includes measurements of the interven‐ tricular septum, left ventricular posterior wall thickness and end-diastolic diameter. Upon these parameters obtained by M-Mode at the end of diastole (under two-dimensional control), the left ventricular mass is calculated according to the proposed formula [12]. Since LV mass is depended on gender and obesity, the thresholds for presence of LVH mass are indexed to body surface area and estimated for men (above 125g/m2 ) and for women (above 110g/m2 ) [10]. The adaptation of the left ventricle to hypertension is heterogenic and can be classified in three geometric patterns based on the LV mass and on the index of relative wall thickness (LV wall thickness / chamber radius). An increased ratio ≥ 0.42 combined with increased mass is referred to as concentric hypertrophy. The term eccentric hypertrophy refers to subjects with normal wall to radius ratio (< 0.42) but increased LV mass. The last pattern, the concentric remodeling, refers to subjects with normal ventricular mass but increased ratio (≥ 0.42). All three types of chamber remodeling in response to hypertension are related to increased cardiovascular risk. Interestingly, the incidence of cardiovascular events correlates with changes in geometric adaptation, independent of changes of the LV mass. The development or the persistence of a concentric geometry during treatment has been found to be associated with a greater incidence of cardiovascular events [13]. In the Losartan Intervention For Endpoint reduction in hyper‐ tension (LIFE) study [11] a regression of the left ventricular mass of about 25g/m2 was associ‐ ated with a 20% reduction in the incidence of the primary endpoint (cardiovascular mortality, myocardial infarction, stroke). Recent data have furthermore reinforced the predictive value of echocardiography in hypertensive patients. 35.000 normotensive and hypertensive partic‐ ipants with normal left ventricular ejection fraction were studied retrospectively. An abnormal left ventricular geometric pattern was found in 46% of the patients (35% with left ventricular concentric remodeling and 11% with LVH) and was associated with a double-risk of all-cause mortality compared to the patients with normal left ventricular geometry [14]. A prospective trial showed that hypertensive patients with echocardiographic LVH had significantly higher all-cause mortality and cardiovascular events [15]. Beyond the lower incidence of cardiovas‐ cular events, including sudden death, in patients with regression of echocardiographic left ventricular hypertrophy or a delayed increase in left ventricular mass [11], treatment-induced changes of left atrium dimension and ventricular geometry are also correlated with cardio‐ vascular event rates [16, 17].

choic liquid components may also be observed. A spectrum of appearances is possible. Pheochromocytomas are bilateral in approximately 10% of cases and extra-adrenal in 10–20%. The organ of Zuckerkandl should be looked for at the level of the origin of the inferior mesenteric artery, anterior to the aorta. Other extra-adrenal sites are the renal hilum, bladder wall, and thorax. Pheochromocytoma is occasionally seen posterior to the renal vein in transverse scans. Rarely, pheochromocytoma is diagnosed in the setting of multiple endocrine neoplasia (MEN). About 2% to 5% of pheochromocytomas are malignant. In recent years

Abdominal ultrasound is also being used in the evaluation of hypertension induced end-organ damage. Vascular end-organ damage may be visualized as atherosclerotic as well as aneur‐ ysmatic wall alterations, e.g. of the aorta. In the elderly (> 65 years) approximately 60% of the patients with hypertension have an isolated systolic hypertension. This is a result of the diminished elasticity of the large arterial vessels. Ultrasound can indicate a morphological correlate in form of a manifest aortosclerosis. Besides vascular end-organ damage abdominal ultrasound detects renal end organ damage. The correlate of hypertensive end-organ damage of the kidney is (benign) nephrosclerosis. The sonographic features include a reduced size, hyperechoic parenchyma, indefinite margin of parenchyma and pyelon, and scarring cortical retractions. As stated above, this unspecific sonographic appearance does unfortunately not

Hypertension is one of the most important risk factors for heart failure with increasing risk in all age groups. The lifetime risk for developing heart failure is doubled for subjects with blood pressure > 160/100mm Hg compared to those with blood pressure < 140/90 mm Hg [8]. Systolic and diastolic heart failure are both associated with hypertension. There are several mecha‐ nisms, alone or in combination, leading to development of heart failure in the presence of hypertension: left ventricular hypertrophy (LVH), chamber remodeling, hemodynamic load and coronary microvascular disease with impaired coronary hemodynamics. To assess subclinical organ damage, such as ventricular hypertrophy, echocardiography is more sensitive than electrocardiography [9], which is a routine examination in all subjects with high blood pressure. However, the ESC/ESH guidelines suggest that in patients with low and intermediate cardiovascular risk an echocardiography should be performed for better global cardiovascular risk stratification which may implicate the appropriate pharmacological treatment [10]. The role of echocardiography is not limited to identification of (sub-) clinical organ damage in the pre-treatment phase. Since changes of the left ventricular hypertrophy in response to treatment are associated to cardiovascular fatal and non-fatal events [11], echo‐ cardiography can also be used to monitor treatment's success and re-assess overall risk.

Left ventricular hypertrophy is the first step toward the development of hypertensive heart disease. The echocardiographic evaluation of LVH includes measurements of the interven‐ tricular septum, left ventricular posterior wall thickness and end-diastolic diameter. Upon

endosopic sonography is being used to obtain an adrenal gland biopsy [5-7].

allow a differentiation between cause and result of hypertension.

**3. Echocardiography**

100 Advancements and Breakthroughs in Ultrasound Imaging

Even before evidence of left ventricular hypertrophy is present and before hypertension in young normotensive male offspring of hypertensive parents has developed, diastolic dys‐ function may develop as an early end organ damage due to hypertension [18]. Patients with diastolic heart failure (also referred as heart failure with preserved ejection fraction) show similar long term impairments as patients with systolic heart failure [19]. The importance of an early recognition of diastolic dysfunction is imperative. Arterial hypertension with or without hypertrophy is the main cause of diastolic dysfunction, namely the inability of the heart to adequately fill with blood during diastole. There are several factors which lead to diastolic dysfunction in hypertension by impeding the active or passive phases of diastole. Of these, contractile alterations in myocytes, structural ventricular hypertrophy, extracellular and perivascular fibrosis, and myocardial ischemia are most often implicated. The European Society of Cardiology has recognized diastolic dysfunction diagnosed by echocardiography as criterion for the diagnosis of diastolic heart failure [20]. There are a number of specific echocardiographic indicators of diastolic dysfunction obtained during the examination. The

major four parameters include transmitral Doppler inflow velocity patterns, pulmonary venous Doppler flow patterns, tissue Doppler velocities and color M-mode flow propagation velocity (Vp). Transmitral Doppler flow is acquired by placing a pulsed wave (PW) sample volume at the level of the tips of the mitral leaflets in the apical four-chamber view. Normally, the ventricular inflow consists of an early (E) and a late filling peak (A). Respectively, the early filling peak velocity (E) and the late (atrial) peak velocity (A) should be recorded. In normal young individuals, more forward flow occurs during the early diastole largely due to the rapid decline in left ventricular pressure during the isovolumetric relaxation time (IVRT). Conse‐ quently, the E/A ratio is > 1 correlating with a normal relaxation. An E/A ratio < 1 together with prolonged IVRT and deceleration time (DT, rapid decline of the E) indicate an abnormal relaxation. By considering these three parameters two more patterns of impaired diastolic function are known: the "pseudonormal" pattern which turns to an impaired relaxation pattern when a Valsalva maneuver is performed and the restrictive pattern. The last one, occurring mostly in patients with restrictive cardiomyopathies (e.g., infiltrative sarcoidosis, endomyocardial fibrosis) and dilated cardiomyopathies with poor systolic function which is associated with increased mortality [21]. Unfortunately, mitral flow is influenced not only by the diastolic properties of the LV but also by other factors, including preload, afterload, heart rate and the presence of arrhythmias. Another indicator, the pulmonary venous flow can be used to assess diastolic function but it is also limited in case of mitral valve disease, heart block and tachycardia. A more precise assessment of the diastolic function can be made by using the tissue Doppler imaging (TDI). This enables the measurement of frequency Doppler shifts caused by myocardial motion as the mitral annulus recoils back toward the base in early (e') and late (a') diastole. The peak waves (e´ and a´) are obtained in analogy to those recorded by the mitral flow. TDI enables, depending of the placement of the sample volume, assessment of global or regional diastolic function. In patients with hypertension and hypertrophy, diastolic dysfunction is more evident at the basal septal segments [22]. The E/e' ratio (with e' assessed at a lateral segment) has been identified as the best parameter for diagnosis of diastolic heart failure [23]. An E/e' ratio below 8 is associated with normal filling pressures and a ratio > 12 to 15 is associated with elevated filling pressures. For values between 8 and 12 additional echocardiographic parameters (e.g., use of Valsalva with transmitral Doppler, pulmonary venous flow) are recommended to correctly classify diastolic function. By using the Doppler color M-mode another index of diastolic dysfunction, the propagation velocity of early diastolic flow (Vp) into the ventricle has been proposed. This index seems to be independent of the load conditions and can be useful to unmask diastolic dysfunction in hypertensive patients with pseudonormal mitral flow. However, in patients with normal left ventricular function the Vp may be normal despite an impaired left ventricular relaxation indicating a major limitation of the index. Beside diastolic dysfunction, an enlarged left atrium was found in patients with hypertension and preserved ejection fraction and is associated with elevated filling pressures of the left ventricle leading to clinical heart failure [24].

however a high level of expertise and is limited by subjectivity. Quantified, objective meas‐ urements of the LV systolic function have become standard practice in echocardiography. One parameters of the systolic function is fractional shortening obtained from M-Mode tracings in the parasternal long axis (method according to Teichmann). Though it is a simple and quick method, it is limited by the fact that it provides information about contractility along a single line. If regional wall motion abnormalities occur (e.g. in the presence of coronary artery disease) the severity of the dysfunction may be under - or overestimated, depending if the region of an abnormal wall motion is interrogated or not. As long as this method is only valid in symmet‐ rically contracting hearts, it is inappropriate for the remodeled ventricles of patients with heart failure. The European and American guidelines recommended the biplane method of discs (modified Simpson's rule) as the echocardiographic method of choice for volume measure‐ ments and estimation of ejection fraction [25, 26]. The principle underlying this method is that the total LV volume is calculated from the summation of a stack of elliptical discs. The height of each disc is calculated as a fraction of the LV long axis based on the longer of the two lengths from the two and four-chamber views. The cross-sectional area of the disk is based on the two diameters obtained from the two- and four-chamber views. The method can also be used with one single plane, when two orthogonal views are not available. In this case, the presence of any extensive wall motion abnormalities may limit the results [25]. Practically, the endocardial borders in the apical 4- and 2-chamber views in end-diastole and end-systole are traced manually or automatically. The end-diastolic and end-systolic volumes (EDV, ESV) are calculated and the ejection fraction is estimated as follows: Ejection fraction = (EDV – ESV) / EDV. The reference values for the ejection fraction do not differ between men und women. An EF > 55% indicates a normal systolic function. An EF between 45-54% suggests a mildly abnormal function and an EF between 30-44% a moderately abnormal systolic function. A severely abnormal left ventricular function is indicated by an EF < 30%. This 2-D approach to assess EF is based on geometric assumptions, which are invalid in a nonsymmetrical contract‐ ing, remodeled ventricle. Over the last decade, several three-dimensional (3-D) echocardio‐ graphic techniques became available to measure LV volumes and mass. 3-D echocardiography does not rely on geometric assumptions for volume/mass calculations and is not subject to plane positioning errors, which can lead to chamber foreshortening. Compared to the goldstandard for assessment of left ventricular volumes and EF, the cardiac magnetic resonance, 3-D echocardiography showed significantly better agreement (smaller bias), lower scatter and lower intra- and inter-observer variability than 2-D echocardiography [27, 28]. Furthermore, 3-D echocardiography is also used in the assessment of diastolic function, as it is independent

Diagnostic Use of Sonography in the Evaluation of Hypertension

http://dx.doi.org/10.5772/56171

103

In summary, echocardiography is a necessary diagnostic tool for risk stratification of pa‐ tients with hypertension before treatment but also for follow-up assessment of end-organ damages during treatment. In 25-30% of hypertensive patients with low or moderate car‐ diovascular risk (based on risk factor evaluation and ECG), an increase of the LV mass may be identified by echocardiography leading to higher risk stratification and changes of

of load conditions.

therapeutic strategy [29, 30].

As described earlier, echocardiography assesses two main features of the hypertensive heart disease, left ventricular hypertrophy and diastolic dysfunction. Systolic dysfunction occurring in the presence or not of the aforementioned changes is assessed in the clinical practice by echocardiography. Assessment of the ejection fraction can be made visually, it requires however a high level of expertise and is limited by subjectivity. Quantified, objective meas‐ urements of the LV systolic function have become standard practice in echocardiography. One parameters of the systolic function is fractional shortening obtained from M-Mode tracings in the parasternal long axis (method according to Teichmann). Though it is a simple and quick method, it is limited by the fact that it provides information about contractility along a single line. If regional wall motion abnormalities occur (e.g. in the presence of coronary artery disease) the severity of the dysfunction may be under - or overestimated, depending if the region of an abnormal wall motion is interrogated or not. As long as this method is only valid in symmet‐ rically contracting hearts, it is inappropriate for the remodeled ventricles of patients with heart failure. The European and American guidelines recommended the biplane method of discs (modified Simpson's rule) as the echocardiographic method of choice for volume measure‐ ments and estimation of ejection fraction [25, 26]. The principle underlying this method is that the total LV volume is calculated from the summation of a stack of elliptical discs. The height of each disc is calculated as a fraction of the LV long axis based on the longer of the two lengths from the two and four-chamber views. The cross-sectional area of the disk is based on the two diameters obtained from the two- and four-chamber views. The method can also be used with one single plane, when two orthogonal views are not available. In this case, the presence of any extensive wall motion abnormalities may limit the results [25]. Practically, the endocardial borders in the apical 4- and 2-chamber views in end-diastole and end-systole are traced manually or automatically. The end-diastolic and end-systolic volumes (EDV, ESV) are calculated and the ejection fraction is estimated as follows: Ejection fraction = (EDV – ESV) / EDV. The reference values for the ejection fraction do not differ between men und women. An EF > 55% indicates a normal systolic function. An EF between 45-54% suggests a mildly abnormal function and an EF between 30-44% a moderately abnormal systolic function. A severely abnormal left ventricular function is indicated by an EF < 30%. This 2-D approach to assess EF is based on geometric assumptions, which are invalid in a nonsymmetrical contract‐ ing, remodeled ventricle. Over the last decade, several three-dimensional (3-D) echocardio‐ graphic techniques became available to measure LV volumes and mass. 3-D echocardiography does not rely on geometric assumptions for volume/mass calculations and is not subject to plane positioning errors, which can lead to chamber foreshortening. Compared to the goldstandard for assessment of left ventricular volumes and EF, the cardiac magnetic resonance, 3-D echocardiography showed significantly better agreement (smaller bias), lower scatter and lower intra- and inter-observer variability than 2-D echocardiography [27, 28]. Furthermore, 3-D echocardiography is also used in the assessment of diastolic function, as it is independent of load conditions.

major four parameters include transmitral Doppler inflow velocity patterns, pulmonary venous Doppler flow patterns, tissue Doppler velocities and color M-mode flow propagation velocity (Vp). Transmitral Doppler flow is acquired by placing a pulsed wave (PW) sample volume at the level of the tips of the mitral leaflets in the apical four-chamber view. Normally, the ventricular inflow consists of an early (E) and a late filling peak (A). Respectively, the early filling peak velocity (E) and the late (atrial) peak velocity (A) should be recorded. In normal young individuals, more forward flow occurs during the early diastole largely due to the rapid decline in left ventricular pressure during the isovolumetric relaxation time (IVRT). Conse‐ quently, the E/A ratio is > 1 correlating with a normal relaxation. An E/A ratio < 1 together with prolonged IVRT and deceleration time (DT, rapid decline of the E) indicate an abnormal relaxation. By considering these three parameters two more patterns of impaired diastolic function are known: the "pseudonormal" pattern which turns to an impaired relaxation pattern when a Valsalva maneuver is performed and the restrictive pattern. The last one, occurring mostly in patients with restrictive cardiomyopathies (e.g., infiltrative sarcoidosis, endomyocardial fibrosis) and dilated cardiomyopathies with poor systolic function which is associated with increased mortality [21]. Unfortunately, mitral flow is influenced not only by the diastolic properties of the LV but also by other factors, including preload, afterload, heart rate and the presence of arrhythmias. Another indicator, the pulmonary venous flow can be used to assess diastolic function but it is also limited in case of mitral valve disease, heart block and tachycardia. A more precise assessment of the diastolic function can be made by using the tissue Doppler imaging (TDI). This enables the measurement of frequency Doppler shifts caused by myocardial motion as the mitral annulus recoils back toward the base in early (e') and late (a') diastole. The peak waves (e´ and a´) are obtained in analogy to those recorded by the mitral flow. TDI enables, depending of the placement of the sample volume, assessment of global or regional diastolic function. In patients with hypertension and hypertrophy, diastolic dysfunction is more evident at the basal septal segments [22]. The E/e' ratio (with e' assessed at a lateral segment) has been identified as the best parameter for diagnosis of diastolic heart failure [23]. An E/e' ratio below 8 is associated with normal filling pressures and a ratio > 12 to 15 is associated with elevated filling pressures. For values between 8 and 12 additional echocardiographic parameters (e.g., use of Valsalva with transmitral Doppler, pulmonary venous flow) are recommended to correctly classify diastolic function. By using the Doppler color M-mode another index of diastolic dysfunction, the propagation velocity of early diastolic flow (Vp) into the ventricle has been proposed. This index seems to be independent of the load conditions and can be useful to unmask diastolic dysfunction in hypertensive patients with pseudonormal mitral flow. However, in patients with normal left ventricular function the Vp may be normal despite an impaired left ventricular relaxation indicating a major limitation of the index. Beside diastolic dysfunction, an enlarged left atrium was found in patients with hypertension and preserved ejection fraction and is associated with elevated

102 Advancements and Breakthroughs in Ultrasound Imaging

filling pressures of the left ventricle leading to clinical heart failure [24].

As described earlier, echocardiography assesses two main features of the hypertensive heart disease, left ventricular hypertrophy and diastolic dysfunction. Systolic dysfunction occurring in the presence or not of the aforementioned changes is assessed in the clinical practice by echocardiography. Assessment of the ejection fraction can be made visually, it requires

In summary, echocardiography is a necessary diagnostic tool for risk stratification of pa‐ tients with hypertension before treatment but also for follow-up assessment of end-organ damages during treatment. In 25-30% of hypertensive patients with low or moderate car‐ diovascular risk (based on risk factor evaluation and ECG), an increase of the LV mass may be identified by echocardiography leading to higher risk stratification and changes of therapeutic strategy [29, 30].
