Should all patients with hypertension have echocardiography?

(2000) 14, 417 421 2000 Macmillan Publishers Ltd All rights reserved 0950-9240/00 $15.00 www.nature.com/jhh REVIEW ARTICLE Should all patients with hypertension have echocardiography? G de Simone 1,2, G Schillaci 3, V Palmieri 1,2 and RB Devereux 2 1 Department of Clinical and Experimental Medicine, Federico II University Hospital, School of Medicine, Naples, Italy; 2 Department of Medicine, The New York Presbyterian Hospital Weill Medical College of Cornell University, New York, NY, USA; 3 Division of Medicine, Beato G. Villa Hospital, Città della Pieve (Perugia), Italy The feasibility of echocardiographic determination of left ventricular (LV) mass, as well as the advantages that might be gained in some clinical circumstances and possible indications are examined in the present review, in relation to the recent WHO/ISH. The information obtained with echocardiograms in arterial hypertension is an important contribution to risk stratification on an epidemiological scale. In clinical practice, under the ascertained condition of a good reliability, an echocardiogram should be recommended as part of the initial work up when patients meet criteria for not starting therapy (low or mild risk WHO-ISH) or in all circumstances in which decision-making might be affected by the echocardiographic result. At present, there is not sufficient evidence to extend the indication of echocardiography also to patients for whom antihypertensive management is already necessitated by identification of high or very high risk status. (2000) 14, 417 421 Keywords: hypertrophy; decision-making; treatment; guidelines; cardiovascular risk Introduction Uncertainty persists regarding the use of echocardiography as a cost-effective routine diagnostic procedure in patients with arterial hypertension. At the time of JNC V, the electrocardiogram was the preferred procedure to detect left ventricular (LV) hypertrophy, although...assessment of cardiac anatomy and function by echocardiography... are additional measures occasionally useful in assessing cardiovascular status in selected cases. 1 JNC V did not mention which selected cases should undergo echocardiographic assessment of LV mass and/or function. This ambiguity, already emphasised, 2 has not been resolved by the most recent national 3,4 and international guidelines. 5,6 The confusion may even have increased because the recent WHO-ISH guidelines 6 mention echocardiography as a tool to detect LV hypertrophy, together with ECG, without additional insights. This vague indication does not take into account the fact that the generalised use of echocardiography to detect LV hypertrophy would double the cost of the initial work-up for arterial hypertension (including ECG), a burden that needs to be proven useful and of additional value in terms of information needed to guide physicians decisions for patient management. Correspondence: Dr Giovanni de Simone, Echocardiography Laboratory, Department of Clinical and Experimental Medicine, Federico II University Hospital, School of Medicine v. S. Pansini 5 80131 Naples, Italy. E-mail: simogi unina.it Received and accepted 29 March 2000 Among the numerous guidelines available at this time, two extreme positions can be highlighted: the Italian Committee for Guidelines on Hypertension and Cardiovascular Diseases suggests the use of echocardiography for LV mass assessment in any patient classified as high risk because of blood pressure values (grades 2 and 3, WHO), and/or associated cardiovascular risk factors (including diabetes, dyslipaemia, previous myocardial infarction (MI), LV hypertrophy at the ECG and/or family history of coronary heart disease), and in any patient in whom LV hypertrophy is likely to be present because of a number of indirect signs (other target organ damage, high average 24 h blood pressure, etc). 3 At the other extreme, the American Heart Association/American College of Cardiology Committee suggested a clearcut indication to the echocardiographic examination only when associated cardiovascular diseases or LV dysfunction were known or likely to be present. 7 At present, in the absence of a clear guideline, the pressure on the echocardiography laboratories for detection of LV hypertrophy is increasing sharply. In the Echo Lab of the Department of Clinical and Experimental Medicine of the Federico II University in Naples, Italy, this indication for echocardiography covers more than 20% of all the referrals, substantially contributing to the length of the waiting list. In this review, we will critically analyse the feasibility of echocardiographic determination of LV mass, as well as the advantages that might be gained in some clinical circumstances and possible indications therefore, in relation to the recent WHO/ISH guidelines. 6

418 Rationale of the detection of LV hypertrophy: epidemiology and clinic There is strong evidence that echocardiographic LV hypertrophy is a potent marker of cardiovascular risk in arterial hypertension, 8 11 independent of cardiovascular risk factors, representing a form of preclinical stage of the cardiovascular disease that enhances sensitivity to triggered events. 12 There is also evidence that event rate may be decreased by reducing LV mass. 13 In addition to determining the degree and pattern of LV hypertrophy, 14 echocardiography also provides prognostically valuable information on LV myocardial function 15 and total arterial compliance. 16 However, the strong prognostic significance of echocardiographic findings does not yield automatically a need to evaluate LV anatomy in every patient, because there is a limited number of circumstances in which the echocardiographic information is likely to influence clinical decision-making. Moreover, while methodologic errors are diluted on epidemiological scale, they might result in major confusion when a single patient is examined. It is also evident, however, that although there is no proof of better management of hypertensive patients, the confidence of doctors in their assessment of patients problems apparently increases when echocardiographic results are available. 2 Determination of LV mass The technical skill for determination of LV mass, as well as of other quantitative parameters, does not necessarily coincide with the general diagnostic ability of an echocardiography laboratory. While the position of patients is the same for all transthoracic procedures (ie, partial left lateral decubitus), the left ventricle is often evaluated from suboptimal low parasternal windows. First, LV M-mode needs to be prepared in a parasternal long axis view, in which the ultrasound beam is perpendicular to the septum and posterior wall. After locating the optimal orientation, the transducer should be rotated by 90 to obtain a short axis view, in which the left ventricle presents a near-perfect circular shape. In this position the ultrasound beam should be directed to cross the antero-posterior diameter (carefully avoiding papillary muscles or chordae and paying attention to lateral shift of the heart during cardiac cycles and breathing which can produce crossing a geometric chorda displaced from the diameter). When M-mode recordings are obtained from an optimal position and orientation of an ultrasound beam, the patient should be requested to hold their breath in expiration for 3 6 cardiac cycles. The sonographer should adjust the gain to avoid excessive blooming of the posterior interface of the posterior wall, while maintaining the ability to distinguish between endocardial interface and chordae or trabeculae. The transducer frequency should be as high as possible to improve endocardial definition, and imaging depth should encompass the posterior pericardium throughout the cardiac cycle. If some of these recommendations are not met, important errors may occur, mainly (though not solely) due to wrong orientation of the ultrasound beam, which can yield erroneous LV internal diameters and wall thicknesses both in diastole and systole. Rather, when the left ventricle cannot be visualised with the right probe-position and ultrasound beam-orientation to obtain an optimal M- mode, LV mass can also be calculated using the linear measures taken from 2D long axis parasternal views. 17 This approach is especially useful in elderly individuals, in whom wide angle views are easier to be obtained from low parasternal windows than from high windows. Estimation of LV mass should follow commonly accepted recommendations of the American Society of Echocardiography, using leading-edge-to-leadingedge M-mode or 2D measurements at onset of QRS. 18 This approach has been validated by necropsy data, with values closely related to necropsy LV weight (r = 0.90), 19 and yields a better approximation of LV mass than other methods. 20 Evidence and prudence in the clinical indications Given the relatively high cost of the procedure, and in the absence of a systematic evaluation of the cost/benefit ratio, echocardiographic examination of patients with arterial hypertension without associated cardiovascular disease is likely to be a useful additional information only in circumstances in which the physician s decision can be changed by echocardiographic evidence (class 1 indication, Table 1). Particular attention should be paid to individuals classified in the low or mild cardiovascular risk category, because, according to both JNV VI and WHO-ISH guidelines, the physician might decide to wait before starting pharmacological treatment 5,6 (Figure 1), a decision that would be perfectly consistent with the results of trials showing good effectiveness of lifestyle modification in mild hypertension and low risk patients. 21 In these patients, detection of LV hypertrophy using the sensitive tool of echocardiography 22 can modify the risk classification, identifying a need for immediate drug treatment. In these cases, echocardiography can be substantially useful to minimise the error of misclassification, leaving untreated patients that should be treated. 23 Abergel et al 24 recently showed Table 1 Indications for use of echocardiography in patients with arterial hypertension Echocardiogram is indicated Echocardiogram is not indicated Presence or probability of associated cardiovascular disease or LV dysfunction. Possibility of changing management strategy as a consequence of echocardiographic findings. At the beginning of treatment to orient therapy. In high risk patients in whom an aggressive treatment is already required.

(40.4%) after (and because of) the echocardiogram, due to the presence of clear-cut LV hypertrophy ( 50.0 g/m 2.7 in men or 47.0 g/m 2.7 in women) or LV concentric remodelling (relative wall thickness 0.45; n = 93). 419 Figure 1 1999 WHO-ISH guidelines for grades 1 or 2 hypertension. The grey frames present the possibility to refrain from antihypertensive treatment, pending re-evaluation. In these cases, echocardiography might be useful to confirm risk stratification and decision to manage patients only with lifestyle modifications. RF, risk factors; BP, blood pressure. that adherence to the 1993 WHO/ISH recommendations leaves untreated a proportion of patients with mild hypertension who instead would have been treated if echocardiographic information on LV geometry was available. As already pointed out, 25 the Abergel paper, although based on old guidelines, appears to reinforce the position that an echocardiogram might be important in patients who apparently do not require pharmacological treatment. This observation may easily be extended to the more recent guidelines, suggesting that echocardiography might usefully be performed in patients assigned a low risk score (Figure 1) due to (a) the absence of non-echocardiographic target organ damage (including negative ECG) and (b) the absence of multiple associated cardiovascular risk factors. In contrast, based on the present evidence, echocardiographic information might be less important and, perhaps, superfluous for decision-making in patients assigned a high risk score but without associated cardiovascular diseases, for whom aggressive treatment is already indicated. Based on the present body of evidence, an echocardiogram does not appear to be indicated to specific type of treatment (a frequent spontaneous indication), because there is not direct evidence that echocardiographic findings can be used to discriminate among the classes of medications. Moreover, with present knowledge, the echocardiogram does not add critical information for decision-making when other information on cardiovascular risk factors and target organ damage already mandates classification of patients in the high or very high risk rank (Table 1). To evaluate the impact of the indications displayed in Table 1, we examined the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study cohort. 11 Among 2373 untreated hypertensive patients one of the indications for echocardiographic examination (class 1 in Table 1) was present in 944 individuals (39.8%). Specifically, 11.4% (n = 271) were classified as low risk and 28.4% (n = 673) as medium risk (WHO-ISH criteria 6 ). Among them, 381 could be reclassified Reliability and feasibility An additional problem to face when considering indications for echocardiographic examination in arterial hypertension is the ability to obtain reproducible measurements. 26 30 Recently, two different trials provided useful insights into this problem, further refining our consciousness when asking for quantitative echocardiographic evaluation in individual hypertensive patients. In the first report, 31 the test-retest reliability of LV mass calculation was assessed in 183 hypertensive patients from the Prospective Randomized Study of Enalapril to Reverse Ventricular Enlargement (68% men 65 ± 9 years) with LV hypertrophy (LV mass 104 g/m 2 in women, 116 g/m 2 in men) by comparing two echocardiograms performed 45 ± 25 days apart. Analyses were based on readings by one experienced reader (intra-observer variability), obtained from measurements taken using optimally oriented M-mode recordings or, in a majority of patients, 2D long-axis parasternal view. Intraclass correlation coefficient for LV mass was 0.93 and 90% confidence interval of the difference in LV mass between the two evaluations was 14% ( 32 g) to +15% (35 g). This variability of LV mass was unrelated to age or betweenevaluation changes in body weight, systolic or diastolic blood pressure or Doppler-stroke volume. In the second study (Reproducibility of Ecocardiographic Studies), 32 two M-mode tracings (three consecutive cycles) were recorded in the same session and 3 10 days apart in 261 subjects (50% hypertensive, 50% women) in 16 centres in Italy and read by two observers in each centre, after classification by a three-order quality-score (1 = poor, 2 = sufficient, 3 = optimal). Intraclass correlation for test-retest variability of LV mass was 0.96. The 90% interval of agreement of the day-to-day, test-retest intraobserver variability was similar to the one reported in PRESERVE: 30 g to 35 g ( 18 to 18%). This variability decreased to 13/12% at the 80% of interval of agreement and 12/11% at the 75% limit (Table 2). Categorical consistency of re-test in identification of LV hypertrophy in hypertensive patients, who had it on the first study, was as high as 87% ( = 0.87). The results of these studies indicate that echocardiographic measurement of LV mass demonstrates good reproducibility for helping stratify risk in single patients with arterial hypertension, when this information is able to modify management strategy. Technical variability of the measure, however, which is mostly randomly distributed, blunts an indiscriminate use of repeated measurements of LV mass in single patients follow-up, to assess efficacy of treatment. When needed, estimation of the likelihood of true biological change needs to take into account method of measurements, reader s skill and experience of the laboratory. When these are appropriate, the data in Table 2 can be used to estimate

420 Table 2 Probability of true biological variation assessed by percentiles of intra-observer test-retest differences in two sequences of three cardiac cycles, 3 to 10 days apart, performed by expert readers Percentiles Day 1 to day 2 Probability of true % difference biological variation (3 cardiac cycles) for greater changes 5 15.15 90% 10 9.90 80% 12.5 8.88 75% 15 8.52 70% 20 6.09 60% 25 4.32 50% 30 2.75 40% 70 5.45 40% 75 6.17 50% 80 7.56 60% 85 9.91 70% 87.5 11.00 75% 90 12.70 80% 95 15.90 90% From Palmieri et al. 31 the likelihood that an observed difference in LV mass between studies represents a true change in the observed duration. Conclusions The body of information provided by echocardiography in arterial hypertension represents an important contribution to risk stratification on an epidemiological scale. 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