Cardiology Research and Practice Table 4: Unadjusted and adjusted hazard ratios of left ventricular relaxation time constant (Tau) > 48 ms and peak early diastolic mitral annular velocity (e ) < 5.8 cm/s by Cox proportional hazards regression analysis. Unadjusted 2.57 (1.13–5.81)¶ 3.47 (1.57–7.70)# Model 1∗ 2.45 (1.04–5.82)¶ 2.38 (1.03–5.52)¶ Adjusted Model 2† 3.12 (1.16–8.37)¶ 4.09 (1.75–9.57)# Model 3‡ 3.23 (1.31–7.97)¶ 3.81 (1.65–8.81)# Data are represented as hazard ratio (95% CI). ∗Adjusted for age, sex, hypertension, dyslipidemia, diabetes, and coronary revascularization after the index cardiac catheterization. †Adjusted for previous history of myocardial infarction, the number of coronary arteries narrowed, ejection fraction, systolic aortic pressure, and heart rate. ‡Adjusted for use of β-blocker, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium blocker, statin, and antiplatelet agents. ¶P < 0.05. #P < 0.01. 6 Tau > 48 ms e < 5.8 cm/s found that EDP > 20 mmHg and E/e ≥ 15 were each predictive of future heart failure events. In contrast, in our study, no prognostic value was observed in EDP or E/e . Compared with a cohort of Liang et al., our patients had lower EDP (18.2 ± 7.3 versus 14.4 ± 5.4 mmHg) and E/e (12.5 ± 5.6 versus 9.6 ± 3.3) levels, due probably to that patients with congestive heart failure were not included in our study. Thus, EDP or E/e may not be predictive of adverse prognosis in a cohort of patients without congestive heart failure in which the majority have normal or slightly elevated EDP and E/e . The strength of the present study is that LV hemody- namic variables were obtained with the use of a micro- manometer catheter but not a ﬂuid-ﬁlled catheter. Although a ﬂuid-ﬁlled catheter accurately measures late diastolic LV pressures, it cannot precisely determine rapidly changing pressures as occur during LV isovolumetric relaxation [17]. Use of a micromanometer catheter enabled us to determine Tau, an index of LV relaxation. Although LV relaxation can be estimated from e on Doppler echocardiography, e quanti- tates the peak velocity of early diastolic longitudinal motion of the mitral annulus [18] and measurement of e only pro- vides best-available noninvasive assessment of LV relaxation. Our study is signiﬁcant in showing for the ﬁrst time the prognostic value of abnormal LV relaxation determined by cardiac catheterization in patients with known or suspected CAD. Although the present study does not provide direct mechanisms underlying the association between abnormal LV relaxation and adverse prognosis in patients with known or suspected CAD, there are possible explanations. The most common cause of cardiac death or cardiovascular hospital- ization in our study was ischemic myocardial events. It is well-established that the presence of myocardial ischemia impairs LV relaxation [19]. In fact, we observed that patients with impaired LV relaxation had more severe CAD (Table 2). Thus, the prognostic association of impaired LV relaxation may be mediated at least in part by CAD severity. We ob- served, however, that after adjustment for the index coronary angiographic ﬁndings, the predictive value of impaired LV relaxation remained signiﬁcant (Table 4, Model 2). Thus, a part of the prognostic association of impaired LV relaxation may be due to inducible myocardial ischemia regardless of the stenoses of epicardial coronary arteries. Consistent with this explanation, studies have shown that impaired LV relaxation diminishes early diastolic coronary ﬂow [20, 21] and may thereby further exaggerate myocardial ischemia particularly when accompanied by tachycardia (such as tachyarrhythmia and during exertion). Another possible explanation for our observed associa- tion of impaired LV relaxation with adverse prognosis is that LV diastolic abnormalities may coexist with other disorders that may adversely impact on prognosis. Speciﬁcally, Lee et al. reported that altered LV diastolic function assessed by Doppler echocardiography was independently associated with endothelial dysfunction and hemostatic abnormalities [22], both of which have been reported to be predictive of the development of atherosclerotic diseases and ischemic myocardial events in patients with CAD [23, 24]. There are several limitations in the present study. First, LV mass was available in the limited number of the patients (68%), which could have inﬂuenced our results [25]. Furthermore, estimation of LV mass by M-mode echocar- diography in the presence of altered LV geometry such as myocardial infarction may be inappropriate [15]. Second, we did not measure left atrial volume index, a powerful pre- dictor for left atrial pressure and clinical outcomes [14, 26]. Third, the time diﬀerence between cardiac catheterization and Doppler echocardiographic examination is not small (about one day). This may explain our observed modest cor- relations of diastolic function indices obtained from cardiac catheterization with those from Doppler echocardiography and may also possibly explain the lack of prognostic value of E/e . Forth, our study patients were composed of stable known or suspected CAD patients without congestive heart failure who were referred for cardiac catheterization for assessment of CAD. Our ﬁndings cannot be extended to other populations. Finally, our study is not large enough to permit us to evaluate the association of LV diastolic dysfunction with speciﬁc causes of death or hospitalization. Our study suggests that measurement of e by Doppler echocardiography may provide useful information for risk stratiﬁcation in known or suspected CAD patients without congestive heart failure. The cut-oﬀ point of e used in the present study, however, is higher than that previously reported. Speciﬁcally, Wang et al. reported that e < 3 cm/s was a powerful predictor for cardiac death in patients with reduced (<50%) EF [8]. Similarly, the same group reported the predictive value of e < 3.5 cm/s for cardiac death in hypertensive subjects with LV hypertrophy [9]. These results