We prospectively studied 74 patients with pulmonary sarcoidosis without overt electrocardiographic (ECG) abnormalities who were referred to our hospital from April 1, 1996 to December 31, 2010. All patients were diagnosed by pulmonologists and referred to the cardiology division for further examination of possible cardiac involvement, even if they had no cardiac symptoms. The diagnosis of pulmonary sarcoidosis was certified on the basis of the fiber-optic bronchoscopy finding of epithelioid, noncaseating granuloma without necrosis. Patients with known cardiac diseases were excluded from the study. We also excluded patients who were taking corticosteroids. All participants underwent SAECG, cardiac echocardiography, and 24-hour ambulatory Holter monitoring. Serum angiotensin-converting enzyme (ACE) and B-type natriuretic peptide (BNP) levels were also evaluated. SAECG records were obtained from the Frank X, Y, and Z leads during sinus rhythm using a Signal Processor DP 1100 (NEC Corporation, Tokyo, Japan). A total of 200 cycles were averaged to obtain a noise level of <0.2 μV. The signals were amplified, digitized, averaged, and bidirectionally filtered with a band-pass filter at frequencies between 40 and 250 Hz. The filtered QRS duration (f-QRS), the root mean square voltage of the terminal 40 ms (RMS40
) in the f-QRS complex, and the duration of low-amplitude signals <40 μV (LAS40
) in the terminal f-QRS complex were measured. In the present study, LP were considered as “positive” if 2 of the following criteria were met: (1) f-QRS ≥ 120 ms, (2) RMS40
< 20 μV, and/or (3) LAS40
> 38 ms. Left ventricular ejection fraction (LVEF) was measured using the Simpson’s method, and early (E) and late (A) peak diastolic velocities were measured using pulsed-wave Doppler echocardiography to assess left ventricular (LV) diastolic function. We evaluated the total number of premature ventricular contractions (PVCs) on 24-hour ambulatory Holter monitoring. Serum ACE levels were measured using a colorimetric method (colorimetric assay kit, Fujirebio Inc., Tokyo, Japan) with p
-leucine as substrate.
Colorimetry of angiotensin-I converting enzyme activity in serum.
Plasma BNP concentrations were determined using a specific immunoradiometric assay for human BNP with commercial kits (Shionoria kit, Shionogi & Co., Ltd. and Kyowa Medex Co., Ltd., Tokyo, Japan). We followed these patients for the evaluation of incidence of cardiac events including cardiac death, arrhythmias, and HF requiring hospital admission and investigated the association of LP with the subsequent development of cardiac events in patients with pulmonary sarcoidosis. Approval for this study was obtained from the institutional review board of Nippon Medical School, and written informed consent was obtained from all patients.
Measurements are presented as mean ± SD or as number (percentage). Univariate and multivariate Cox proportional hazards regression analyses were performed to relate clinical parameters to the end point. The proportional hazard assumption was assessed graphically using log-log survival plots. Event-free rates in patients with and without LP were calculated using the Kaplan-Meier method, and the difference between them was compared using the log-rank test. A P value of <.05 was considered significant. Statistical calculations were performed using SPSS version 20 (IBM Inc., Chicago, IL).