Mechanisms of False Positive Exercise Electrocardiography: Is False Positive Test Truly False?

Transcription

1 Mechanisms of False Positive Exercise Electrocardiography: Is False Positive Test Truly False? Masaki Izumo a, Kengo Suzuki b, Hidekazu Kikuchi b, Seisyo Kou b, Keisuke Kida b, Yu Eguchi b, Nobuyuki Azuma b, Yoshihiro J Akashi b, Kazuto Omiya b, Fumihiko Miyake b, Takahiro Shiota a. a Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, USA b Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan ESC Congress 2011 Paris

2 Disclosures Dr. Masaki Izumo: None Dr. Kengo Suzuki: None Mr. Hidekazu Kikuchi: None Dr. Seisyo Kou: None Dr. Keisuke Kida: None Dr. Yu Eguchi: None Dr. Nobuyuki Azuma: None Dr. Yoshihiro J Akashi: None Dr. Kazuto Omiya: None Pr. Fumihiko Miyake: None Pr. Takahiro Shiota: None

3 Background Treadmill exercise electrocardiographic test (TET) is the classical method for initial assessment of coronary artery disease (CAD). However, a significant number of patients reveal false positive with this method. The mechanism of false positive TET remains unclear.

4 Background Long term prognosis is poorer in male patients with false positive than aged-matched controls. Erikssen J et al. Circulation 1983;68:

5 Background Recently-introduced speckle tracking echocardiography (STE) quantifies myocardial deformation in the longitudinal, circumferential, and radial directions. Langeland S, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005; 112: Global longitudinal strain (GLS) calculated with this modality was reported to detect early left ventricular (LV) systolic dysfunction despite of normal ejection fraction. Wang J et al. Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. Eur Heart J 2008; 29:

6 Background Strain = Lr-L0 / L0

7 Hypothesis We hypothesized that male false positive patients might have diastolic and subclinical systolic dysfunction, and STE could detect these dysfunction.

8 Study population 755 pts who underwent treadmill exercise test prior cardiovascular surgery, documented myocardial infarction, valvular heart diseases, complete left branch block in electrocardiography, depressed LVEF, atrial fibrillation. (All n=69) 133pts (19.4%); Positive study 553pts (80.6%); Negative study Evaluated by nuclear medicine; 30pts (22.6%) False positive; 36pts (27.1% male; 30pts, female 6pts) True positive; 67pts (50.4%) Single vessel disease; 30pts (22.6%) Multi vessel disease; 37pts (27.8%) Aged-matched control; 30pts False positive in men; 30pts True positive in men; 55pts

9 Methods Treadmill exercise test All patients underwent symptoms-limited TET according to one of the standard protocols (usually Bruce, modified Bruce, or Ramp). This study adopted the standard end points; to halt the exercise test was determined on a basis of fatigue, severe angina, ECG changes compatible with myocardial ischemia, hypertension (systolic BP 220 mmhg), hypotension (decrement of systolic BP 20 mmhg), or significant arrhythmias. Positive TET was defined as horizontal or down sloping ST depression of 1mm below the baseline or ST elevation of 1 mm above the baseline 80 ms after the J point.

10 Methods Two-dimensional echocardiography Echocardiography was performed using a commercially available system (Vivid E9 Dimension, GE Health care, Horten, Norway) equipped with a 3.5-MHz transducer within 2 days before or after TET. Global longitudinal, circumferential, and radial strain were calculated offline using EchoPack software (GE Health care, Horten, Norway) to evaluate LV systolic function.

11 Tissue Doppler Imaging S E (cm/s) S (cm/s) E/E E Tissue Doppler imaging measured peak early diastolic mitral annular velocity (E ) and systolic velocity (S ), and E/E was calculated as E divided by E.

12 Speckle tracking imaging Global longitudinal strain The endocardial border was manually traced in the end-systolic frame using commercially available 2D strain software. Speckles were tracked frame by-frame throughout the LV wall during the cardiac cycle. Longitudinal strain was measured in a 16-segment LV model from apical views; 4-chamber, 2- chamber, and 3-chamber views.

13 Global circumferential and radial strain Circumferential strain Global circumferential strain (GCS) and global radial strain (GRS) were obtained from the average of strain values, including basal, middle and apical levels. Radial strain

14 Clinical and treadmill exercise test data Variables Controls False positive P value Age 60.6± ± Body mass index 23.7± ± Hypertension (%) Smoking (%) Diabetes (%) Dyslipidemia (%) LV hypertrophy (%) Ex duration (min) 7.5± ± SBP at rest (mmhg) 128.8± ± DBP at rest (mmhg) 85.6± ± SBP peak ex (mmhg) 185.6± ± DBP peak ex (mmhg) 94.2± ± HR at rest (bpm) 79.4± ± HR peak ex (bpm) 153.8± ± Mean predicted HR (%) 92.4± ± ST level (mv) 0.08± ±0.13 <0.001

15 Conventional echocardiographic findings Controls False positive True positive P value (ANOVA) LVDd (mm) 44.4± ± ±5.1* LVDs (mm) 27.8± ± ±5.6* EDVI (ml/m 2 ) 57.1± ± ±13.6* <0.001 ESVI (ml/m2) 19.1± ± ±10.5* <0.001 EF (%) 68.0± ± ±10.2* IVSD 9.4± ± ± PWD 9.5± ± ± LV mass index (g/m 2 ) 85.6± ± ± LAVI 19.5± ± ± E/A 1.16± ± ±0.30* *; Significant difference (p<0.05) Control vs. True positive, ; Significant difference (p<0.05) False positive vs. True positive LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter; EDVI, end diastolic volume index; ESVI, end systolic volume index; EF, ejection fraction; IVS, interventricular septal dimension; PWD, posterior wall dimension; LAVI, left atrial volume index.

16 Comparison of advanced echocardiographic findings P=0.002 P= P=0.006 P=ns P=ns P=ns E' (cm/s) ± ± ±2.1 E/E' ± ± ±2.1 Controls False positive True positive Controls False positive True positive P= P=0.013 P=0.215 S' (cm/s) ± ± ±1.2 Controls False positive True positive

17 Comparison of advanced echocardiographic findings Global longtudinal strain (%) P<0.001 P<0.001 P= ± ± ±2.3 Controls False positive True positive Global circumferential strain (%) P=0.043 P=ns P=ns -23.4± ± ±4.3 Controls False positive True positive Global radial strain (%) P=0.032 P=ns P=ns 43.2± ± ±6.6 Controls False positive True positive

18 Determinants of false positive TET Univariate Multivariate OR (95%CI) P value OR (95%CI) P value EF 1.03 ( ) LV mass index 0.92 ( ) E' 1.14 ( ) ( ) S 1.44 ( ) ( ) GLS 1.48 ( ) ( ) GCS 1.13 ( ) ( ) GRS 0.94 ( ) 0.488

19 Echocardiographic parameters predict positive exercise test. 100 Sensitivity (%) Specificity (%) Global longitudinal strain S E AUC Cut-off Sensitivity Specificity E' 0.75 <6.8cm/s S' 0.72 <6.7cm/s GLS 0.79 >-20.3%

20 Results The incidence of false positive results (27.1%) was similar to that of the earlier study. No significant differences in clinical and exercise characteristics except ECG changes were observed between the two groups. Both LV diastolic and subclinical systolic dysfunction were independently related to false positive TET

21 Clinically silent Clinically recognized Discussion Ischemic cascade Coronary flow reserve Endotherial function Camici PG, et al. Circulation 1992 Rigo F, et al. AJC 2002 Angina ECG abnormalities Systolic dysfunction Strain abnormalities Diastolic dysfunction Perfusion abnormalities Time/Magnitude ischemia Asimul A, Puthumana J. Echocardiography in acute coronary syndrome 2009

22 Conclusions Speckle-tracking and tissue Doppler echocardiography detected LV diastolic and subclinical systolic dysfunction in patients with false positive TET.