ONLINE DATA SUPPLEMENT. Impact of Obstructive Sleep Apnea on Left Ventricular Mass and. Diastolic Function

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ONLINE DATA SUPPLEMENT Impact of Obstructive Sleep Apnea on Left Ventricular Mass and Diastolic Function Mitra Niroumand Raffael Kuperstein Zion Sasson Patrick J. Hanly St. Michael s Hospital University of Toronto Ontario, Canada

The ECG and heart rate were monitored using standard limb leads. Airflow was detected by monitoring expired carbon dioxide at the nose and mouth through cannulae adapted for the purpose and attached to a CO 2 analyzer (CD 102 Normocap; Datex Corp., Helsinki, Finland). Respiratory efforts were monitored by inductance plethysmography with transducers placed around the chest and abdomen (Respitrace; Ambulatory Monitoring, Ardsley, NY). Arterial oxygen saturation was measured continuously by pulse oximetry, using a finger probe (Biox 3740; Ohmeda, Boulder, CO) set at the fastest response. All variables were recorded either on a polygraph (model 78E; Grass Instruments, Quincy, MA) at a paper speed of 10 mm/s which was used for sleep studies before September 1993 or on a computerized system (Sandman; Mallinckrodt/Nellcor Puritan Bennet [Melville] Ottawa, Ontario) after September 1993. Obstructive apnea was defined as the absence of airflow for more than 10 s in the presence of continued respiratory effort. Central apnea was defined as the absence of airflow for more than 10 s due to loss of respiratory effort. Hypopneas were defined as a reduction in the amplitude of respiratory effort to between 10% and 50% of the sleeping baseline level for more than 10 s and were classified as central or obstructive events based on the presence of synchronous or paradoxical breathing,

respectively. The apnea--hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep. The standard M-mode measurements of left ventricular wall thickness (LVW) and internal dimensions at end diastole (LVD) were made from the parasternal long axis view as recommended by the American Society of Echocardiography (E1). Left ventricular mass (LVM) was calculated using the Devereux (E2) formula as follows: LVM = 0.8{1.04 [(LVD + IVS + LVPW) 3 - (LVD) 3 ]} + 0.6 where LVD is the left ventricular dimension, IVS is the thickness of the interventricular septum, and LVPW is the thickness of the left ventricular posterior wall. LVM was corrected for the patient s height (LVM/ht). Left ventricular systolic function was assessed by a semiquantitative twodimensional echocardiographic scale of 1 to 4, where grade 1 is normal (ejection fraction > 60%) and grade 4 indicates severe LV dysfunction (ejection fraction < 20%). Left ventricular systolic function was also assessed by M-mode measurements of fractional shortening (FS) (E3, E4) as follows: FS (%) = [LVD (end-diastole) - LVD (end-systole)] / LVD (end-diastole)

Left ventricular ejection fraction was derived from M-mode measurements of ventricular dimensions (E4, E5) as follows: EF (%) = [LVD (end-diastole)] 3 - [LVD (end-systole)] 3 / [LVD (end-diastole)] Left ventricular diastolic function was assessed by pulsed Doppler of transmitral flow from the apical view, with a sample volume at the mitral leaflet tips level so as to obtain the higher E point velocity. The Advanced Technology Laboratories Ultramark 8 (ALT-8) ultrasound system was used. This method of assessing left ventricular filling is well-established and has been validated against contrast and radionuclide angiography (E6, E7). The variables measured include peak early filling velocity (E) and peak late filling velocity (A), from which the E/A ratio is calculated, which is a measure of left ventricular filling in early versus late diastole. Each parameter was measured at end-expiration and averaged over at least 5 consecutive analyzable beats.

References E1. Sahn DJ, De Maria A, Kisslo J, Weymann A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072-1083. E2. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation 1977;55:613-618. E3. Quinones MA, Pickering E, Alexander JK. Percentage of shortening of the echocardiographic left ventricular dimension: its use in determining ejection fraction and stroke volume. Chest 1978;74:59-65. E4. Feigenbaum H. Echocardiographic evaluation of cardiac chambers. In: Fiegenbaum H, editor. Echocardiography. Philadelphia: Lea and Febiger; 1980. p. 119-187. E5. Feigenbaum H, Popp RL, Wolfe SB, Troy BL, Pombo JF, Haine CL, Dodge HT. Ultrasound measurements of the left ventricle: a correlative study with angiocardiography. Arch Int Med 1972;129:461-467. E6. Nishimura RA, Abel MD, Hatel LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Dopplerechocardiography, II: clinical studies. Mayo Clin Proc 1989;64:181-204. E7. Bessen M, Gardin JM. Evaluation of left ventricular diastolic function. Cardiol Clin 1990;8:315-332.

Table E1: LVM in OSA and non-osa Patients without nocturnal hypoxemia Males Females OSA Non-OSA OSA Non-OSA (n=224) (n=96) (n=43) n=40 Age 46.1 + 11.1* 43 + 10.6 48.9 + 10.9 39.5 + 11.4 BMI, kg/m 2 32.3 + 6.6 27.8 + 4.2 34.9 + 8.2 30.6 + 8.9 AHI, hr 34 + 25.5 0.61 + 1.1 25 + 22 0.56 + 1.25 SaO 2 < 90% (%TST) 19.6 + 25.3 0.96 + 1.99 13.7 + 22.5 0.95 + 1.95 LVM/ht, g/m 98.9 + 25.6 91 + 21 90.3 + 21.1 82 + 20 Definition of abbreviations: OSA = obstructive sleep apnea; BMI = body mass index; AHI = apnea-hypopnea index; SaO 2 < 90% (TST) = duration that oxygen saturation was less than 90% during sleep, expressed as percentage of the total sleep time. Data are mean ± SD; *p = 0.021 versus non-osa; p < 0.001 versus non- OSA; p < 0.025 versus non-osa; p = 0.008 versus non-osa; p = 0.07 versus non-osa

Table E2. LVM and E/A ratio in non-obese Men with and without OSA OSA (n=35) Non-OSA (n=35) Age 51 ± 13* 45 ± 11 AHI 22 ± 22 3 ± 1 BMI, kg/m 2 23.5 ± 1.4 25.6 ± 2.7 LVM/ht, g/m 83.7 ± 19.3 84.7 ± 17.4 E/A ratio 1.36±0.42 1.34±0.34 Data are mean ± SD; *p = 0.037 versus non-osa; p < 0.001 versus non- OSA