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82197992.Pdf View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Journal of the American College of Cardiology Vol. 38, No. 2, 2001 © 2001 by the American College of Cardiology ISSN 0735-1097/01/$20.00 Published by Elsevier Science Inc. PII S0735-1097(01)01378-X Relationship of the Electrocardiographic Strain Pattern to Left Ventricular Structure and Function in Hypertensive Patients: The LIFE Study Peter M. Okin, MD, FACC,* Richard B. Devereux, MD, FACC,* Markku S. Nieminen, MD, PHD, FACC,† Sverker Jern, MD,‡ Lasse Oikarinen, MD, PHD,† Matti Viitasalo, MD, PHD,† Lauri Toivonen, MD, PHD,† Sverre E. Kjeldsen, MD, PHD,§ Stevo Julius, MD, SCD, FACC,࿣ Bjo¨rn Dahlo¨f, MD, PHD,‡ for the LIFE Study Investigators New York, New York; Helsinki, Finland; Go¨teborg, Sweden; Oslo, Norway; and Ann Arbor, Michigan OBJECTIVES This study was designed to assess the relation of electrocardiographic (ECG) strain to increased left ventricular (LV) mass, independent of its relation to coronary heart disease (CHD). BACKGROUND The classic ECG strain pattern, ST depression and T-wave inversion, is a marker for left ventricular hypertrophy (LVH) and adverse prognosis. However, the independence of the relation of strain to increased LV mass from its relation to CHD has not been extensively examined. METHODS Electrocardiograms and echocardiograms were examined at study baseline in 886 hyperten- sive patients with ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage enrolled in the Losartan Intervention For End point (LIFE) echocardiographic substudy. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. RESULTS Strain occurred in 15% of patients, more commonly in patients with than without evident CHD (29%, 51/175 vs. 11%, 81/711, p Ͻ 0.001). When differences in gender, race, diabetes, systolic pressure, serum creatinine and high density lipoprotein cholesterol were controlled, strain on baseline ECG was associated with greater indexed LV mass in patients with (152 Ϯ 33 vs. 131 Ϯ 32 g/m2,pϽ 0.001) or without CHD (131 Ϯ 24 vs. 119 Ϯ 22 g/m2,pϽ 0.001). In logistic regression analyses, strain was associated with an increased risk of anatomic LVH in patients with CHD (relative risk 5.14, 95% confidence interval [CI] 1.16 to 22.85, p ϭ 0.0315), without evident CHD (relative risk 2.91, 95% CI 1.50 to 5.65, p ϭ 0.0016), and in the overall population when CHD was taken into account (relative risk 2.98, 95% CI 1.65 to 5.38, p ϭ 0.0003). CONCLUSIONS When clinical evidence of CHD is accounted for, ECG strain is likely to indicate the presence of anatomic LVH. Greater LV mass and higher prevalence of LVH in patients with strain offer insights into the known association of the strain pattern with adverse outcomes. (J Am Coll Cardiol 2001;38:514–20) © 2001 by the American College of Cardiology The classic strain pattern of ST depression and T-wave ship of ECG strain to LV mass, as opposed to its potential inversion on the rest electrocardiogram (ECG) is a well- relation to CHD, has not been extensively examined. Thus, recognized marker of the presence of anatomic left ventric- the present study examined the relation of the strain pattern ular hypertrophy (LVH) (1–6). This abnormality of repo- on the rest ECG to LV mass and the presence of anatomic larization has been associated with an adverse prognosis in a LVH, taking into account potential effects of coexistent variety of clinical populations (7–11) and implicated as the CHD and controlling for other clinical and demographic strongest marker of untoward outcomes when ECG LVH variables that could potentially affect these relationships. criteria have been utilized for risk stratification (8–10). Moreover, the strain pattern could also reflect underlying METHODS coronary heart disease (CHD), a relationship that could in part explain the clinical consequences of this ECG finding Subjects. The Losartan Intervention For End point beyond those directly attributable to high left ventricular (LIFE) study (12,13) enrolled hypertensive patients with (LV) mass (3,4,8,10). However, the independent relation- ECG LVH by Cornell voltage-duration product (14,15) and/or Sokolow-Lyon voltage (1) on a screening ECG in a From the *Department of Medicine, Division of Cardiology, Cornell University prospective double-blind study to determine whether appre- Medical Center, New York, New York; †Division of Cardiology, Department of ciable reduction in mortality and morbid events is associated Medicine, Helsinki University Central Hospital, Helsinki, Finland; ‡Sahlgrenska University Hospital/O¨ stra, Go¨teborg, Sweden; §Ullevål University Hospital, Oslo, with the use of losartan as opposed to atenolol (12). Eligible Norway; and the ࿣University of Michigan Medical Center, Ann Arbor, Michigan. patients for LIFE were hypertensive men and women aged Supported in part by grant COZ-368 from Merck and Co., Inc., West Point, 55 to 80 years with a seated blood pressure of 160 to 200/95 Pennsylvania. Manuscript received November 10, 2000; revised manuscript received March 1, to 115 mm Hg after one and two weeks on placebo. Study 2001, accepted April 10, 2001. inclusion and exclusion criteria have been previously pub- JACC Vol. 38, No. 2, 2001 Okin et al. 515 August 2001:514–20 Strain and Hypertrophy LV mass index was Ͼ104 g/m2 in women or Ͼ116 g/m2 Abbreviations and Acronyms in men. Hypertrophy was considered concentric if LV ASE ϭ American Society of Echocardiography relative wall thickness was Ͼ0.430 and eccentric if relative CHD ϭ coronary heart disease wall thickness was normal (16); patients with normal LV ECG ϭ electrocardiogram, electrocardiographic ϭ mass were considered to have normal LV geometry if ESS end-systolic stress Յ HDL ϭ high density lipoprotein relative wall thickness was 0.43 or to have concentric LIFE ϭ Losartan Intervention For End point study remodeling if relative wall thickness was increased. Alter- LV ϭ left ventricular native analyses used LV mass/height2.7 partition values of LVH ϭ left ventricular hypertrophy 46.7 and 49.2 g/m2.7 in women and men, respectively. Myocardial contractile performance was assessed by ex- amining LV systolic shortening in relation to circumferen- lished (12,13). A previously described (16) representative tial end-systolic stress (ESS) (26). The relation of LV sample of the whole LIFE study, totaling 964 patients, midwall shortening to midwall circumferential ESS at the underwent baseline echocardiograms; 21 patients had un- LV minor axis was calculated as previously described (27), measurable echocardiographic LV mass and 57 had incom- and was expressed as a percent of the value predicted from plete baseline ECG measurements. There were 361 eligible circumferential ESS by an equation derived in apparently women and 525 eligible men whose mean age was 66 Ϯ 7 normal adults (28). This variable, stress-corrected midwall years. shortening was considered low if Ͻ89.2%, the 5th percentile Electrocardiography. All ECGs were interpreted at the in a separate reference population of 280 normal adults (28). Core Laboratory at Sahlgrenska University Hospital/O¨ stra To estimate myocardial oxygen demand, the ESS-LV in Go¨teborg, Sweden, by investigators blinded to the mass-heart rate product was calculated as previously de- clinical information (12,13). The product of QRS dura- scribed (29). Fractional and midwall shortening could be ϫ ϩ tion Cornell voltage (RaVL SV3, with 8 mm added in determined in 100% of patients, whereas circumferential women [14,15]) was used with a threshold value of ESS, stress-corrected midwall shortening and ESS-LV 2,440 mm ⅐ ms to identify LVH. After design of LIFE, mass-heart rate product could be determined in 97% (857/ studies were published suggesting a smaller gender adjust- 886) of patients in this study. ment (6,17), and feedback from LIFE investigators showed Statistics. Patients were classified as having CHD if they that otherwise eligible patients had ECG LVH by highly had self-reported angina or myocardial infarction, diagnos- specific but insensitive Sokolow-Lyon voltage criteria (1), tic Q-waves by Minnesota code on the ECG or segmental but not by Cornell product. Accordingly, changes were wall motion abnormalities on the two-dimensional echocar- made in ECG entry criteria: the gender adjustment of diogram. Differences in prevalence were compared using ␹2 Cornell voltage was reduced from 8 to 6 mm and Sokolow- analyses and mean values of continuous variables by un- ϩ Ͼ Lyon voltage (SV1 RV5/6) 38 mm was accepted for paired t test. Echocardiographic variables were further ECG eligibility (13). Additional ECG measurements were compared using analysis of covariance to adjust for differ- performed at Helsinki University Central Hospital. Repo- ences in age, gender, race, systolic pressure, cholesterol and larization abnormalities in leads V5 and/or V6 indicated high density lipoprotein (HDL) cholesterol, creatinine and typical strain (11) when there was a downsloping convex ST prevalent diabetes between groups. Independent relations of segment with an inverted asymmetrical T-wave opposite to echocardiographic LVH, abnormal LV geometry and ab- the QRS axis. normal stress-corrected midwall shortening to ECG strain Echocardiography. Studies were performed using funda- were determined using stepwise logistic regression analyses mental imaging with commercially available phased-array and the same covariates. A two-tailed p Ͻ 0.05 was required echocardiographs as previously described (16,18). Left ven- for statistical significance. tricular internal dimension and wall thicknesses were mea- sured at end-diastole by American Society of Echocardiog- RESULTS raphy (ASE) recommendations (19) on up to three cardiac cycles. When M-mode recordings could not be optimally Patient characteristics. Strain was present in 132 patients oriented, correctly oriented linear dimension measurements (15%) and was more common in patients with CHD than in were made using two-dimensional imaging by leading-edge those without (29%, 51/175 vs.
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