Enhanced coronary calcification determined by electron beam CT is strongly related to endothelial dysfunction in patients with suspected coronary artery disease.

BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT) is strongly associated with total plaque burden but is not related to systemic vascular inflammation. AIMS: We sought to test the hypothesis that enhanced coronary artery calcification, a marker of atherosclerosis and plaque burden, was related to endothelial dysfunction in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with suspected CAD were enrolled. Coronary artery calcification was detected by EBCT. A noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All subjects were classified into three groups according to coronary calcium scores: group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores > or = 200 (n = 48). There was an inverse association between the degree of coronary artery calcification and the endothelium-dependent FMD in the three groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001) but not the endothelium-independent NMD. Besides, no significant difference in serum levels of hsCRP and MCP-1 were found among the three groups. However, both the serum levels of hsCRP and MCP-1 were correlated significantly with endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037, respectively). By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION: Enhanced coronary artery calcification strongly predicted endothelial dysfunction in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were significantly correlated with endothelial function. These findings suggested that both calcium deposition and inflammation were involved in endothelial dysfunction.

Efficacy and safety of slow-release fluvastatin 80 mg daily in Chinese patients with hypercholesterolemia.

BACKGROUND: Before this study, the efficacy and safety of doubling the dosage of fluvastatin from 40 mg/day to 80 mg/day in Chinese patients with primary hypercholesterolemia remained to be determined. METHODS: In this open-label, active-controlled randomized 2-center study, patients with primary hypercholesterolemia were randomized to treatment with immediate-release fluvastatin 40 mg/day (n = 30) or slow-release fluvastatin 80 mg/day (n = 31) for 12 weeks. The primary efficacy variable was percent change in low-density lipoprotein (LDL) cholesterol level from baseline. Secondary efficacy variables were percent changes in total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels, and the percent of patients achieving LDL cholesterol goals of the US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) II. RESULTS: Both fluvastatin dosages (40 mg/day vs 80 mg/day) effectively reduced LDL cholesterol (-22.5% vs -29.9%; p = 0.087), total cholesterol (-17.3% vs -22.5%; p = 0.140), and triglyceride levels (-14.0% vs -12.3%; p = 0.813) (all p < 0.0001 for comparison with baseline), and slightly increased HDL cholesterol levels (+5.2% vs +5.6%; p = 0.917), after 12 weeks of treatment. The percent of patients achieving LDL cholesterol goals of the NCEP ATP II was 37% versus 65% (p < 0.05). The adverse event profiles for the 2 fluvastatin dosages were similar. CONCLUSION: In Chinese patients with primary hypercholesterolemia, doubling the dosage of fluvastatin from 40 to 80 mg once daily was effective and safe regarding reduction of LDL cholesterol level, and allowed more patients to achieve LDL cholesterol goals of the NCEP ATP II.

Effects of sildenafil on cardiac repolarization.

OBJECTIVES: Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. METHODS: We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. RESULTS: Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). CONCLUSIONS: Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Usefulness of attenuated heart rate recovery immediately after exercise to predict endothelial dysfunction in patients with suspected coronary artery disease.

Attenuated heart rate recovery after graded exercise, which is associated with decreased vagal activity, is a powerful predictor of overall mortality. Endothelial function plays a key role in determining the clinical manifestations of established atherosclerotic lesions and has shown to be suppressed by increased sympathetic tone. We designed this study to determine whether patients with an attenuated heart rate recovery after exercise could predict endothelium dysfunction. Sixty-six patients with suspected coronary artery disease were enrolled, and a noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerin-mediated vasodilation. The patients were divided equally into 3 groups according to heart rate recovery in 1 minute after peak exercise (n = 22 in each group): group 1 had heart rate recovery of /=29 beats. The endothelium-dependent flow-mediated vasodilation responses were significantly decreased in group 1 compared with groups 2 and 3 (2.5 +/- 3.0 vs 5.0 +/- 3.4 vs 5.4 +/- 2.7%, p = 0.006), but responses to sublingual nitroglycerin showed no difference among the 3 groups (p = 0.332). According to multivariate analysis, heart rate recovery after exercise was an independent predictor of endothelial function.

The extracellular fluid-to-intracellular fluid volume ratio is associated with large-artery structure and function in hemodialysis patients.

BACKGROUND: Large-artery derangement is a major risk factor for cardiovascular and all-cause mortality in patients with end-stage renal disease (ESRD). It is not clear how body fluid distribution affects large-artery structure and function in patients with ESRD. METHODS: One hundred fifty-seven hemodialysis (HD) patients (mean age, 55.9 +/- 15.1 years; 76 men, 81 women) were enrolled. Influence of the extracellular fluid (ECF)-to-intracellular fluid (ICF) ratio derived from bioimpedance spectroscopy on the structure and function of the common carotid artery (CCA) and aorta was analyzed. One hundred forty-four healthy subjects were examined to obtain normal reference values for body fluid compartments. Based on ECF-ICF ratio, 2 groups were identified: ECF-ICF ratio in the 95th percentile or less and ECF-ICF ratio greater than the 95th percentile of age- and sex-stratified normal reference values. RESULTS: ECF-ICF ratio was significantly related to CCA diameter (r2 = 0.26; P < 0.001), CCA incremental modulus (E(inc); r2 = 0.15; P < 0.001), carotid augmentation index (AGI; r2 = 0.10; P < 0.001), and aortic pulse wave velocity (aPWV; r2 = 0.21; P < 0.001). ECF-ICF ratio remained a significant independent determinant for CCA diameter (model r2 = 0.47; P < 0.001), E(inc) (r2 = 0.29; P < 0.001), aPWV (r2 = 0.51; P < 0.001), and AGI (r2 = 0.40; P < 0.001) when age, sex, mean blood pressure, anthropometrical parameters, HD duration, and status of diabetes mellitus were accounted for. HD patients with an ECF-ICF ratio greater than the 95th percentile had a greater CCA diameter, E(inc), aPWV, and AGI than their counterparts. CONCLUSION: ECF-ICF ratio is associated with large-artery structure and function in HD patients. Patients with ESRD with a high ECF-ICF ratio are characterized by significant large-artery derangement.

Comparison of hemostatic activation created by right- and left-heart radiofrequency catheter ablation.

BACKGROUND: Thromboembolic complications commonly occur in radiofrequency (RF) ablation procedures (0.6-1.3% of cases). Comparison of hemostatic activation between left and right RF ablation is limited. HYPOTHESIS: The purpose of this study was to evaluate platelet and hemostatic activation before, immediately after, and 48 h following left and right myocardial RF ablation procedures. METHODS: The subjects were two groups of patients who underwent right-heart (24 patients) and left-heart (20 patients) RF ablation. Blood samples taken before, immediately after, and 48 h after the procedure were tested for changes in platelet and hemostatic activation. RESULTS: No indication of clinically symptomatic thromboembolism and no major differences in baseline characteristics and procedure were apparent in either group, except for a higher temperature mode setting (p < 0.001) in the left-heart group. The hemostatic evaluation levels increased significantly by the end of the procedure in both groups and the platelet activation level remained elevated for 48 h after the procedure. The platelet activation level increased insignificantly at the end and 48 h after the procedure. Of the other changes in levels of platelet and hemostatic activation, only an increase in one of the hemostatic levels in the right-heart group at 48 h after procedure was significant (p = 0.01). CONCLUSIONS: Our findings suggest that similar hemostatic activation occurred during and immediately after RF ablation in both groups. Sustained elevation of the hemostatic marker after the ablation procedure in the right-heart group was observed as of significant therapeutic and prognostic implications.

Endovascular stenting treatment for drug-refractory hypertension due to ostial stenosis of transplanted renal artery.

Transplanted renal artery stenosis (TRAS) is one of the major causes of poor blood pressure control, progressive renal dysfunction and finally renal graft failure in uremic patients receiving renal allograft transplantation. Percutaneous transluminal balloon angioplasty (PTA) with stenting is an effective treatment for TRAS but has rarely had validation for the ostial lesions of TRAS. We reported 2 patients developing drug-refractory hypertension along with impaired renal function who received PTA plus stent deployment therapy for severe ostial stenosis of graft renal artery. Both of the patients had improved allograft function gradually, and satisfactory blood pressure control after 3 months follow-up. In conjugation with balloon angioplasty, stenting could provide a safe and effective revascularization strategy in conjunction with balloon angioplasty for ostial lesions of TRAS.

Estimation of central systolic blood pressure using an oscillometric blood pressure monitor.

Current noninvasive techniques for assessing central aortic pressure require the recording of an arterial pressure wave using a high-fidelity applanation tonometer. We therefore developed and validated a novel method to estimate the central aortic systolic pressure using an oscillometric blood pressure monitor alone. Invasive high-fidelity right brachial and central aortic pressure waves, and left-brachial pulse volume plethysmography from an oscillometric blood pressure monitor, were obtained at baseline and 3 min after administration of sublingual nitroglycerin in 100 patients during cardiac catheterization. In the initial 50 patients (Generation Group), Central systolic blood pressure was predicted by a multi-variate prediction model generated from the comprehensive analysis of the invasive brachial pressure wave, including brachial late-systolic shoulder pressure value and parameters related to wave reflection and arterial compliance. Another prediction model was similarly constructed from the noninvasively calibrated pulse volume plethysmography. Both models were validated in the subsequent 50 patients (Validation Group) with results: r=0.98 (P<0.001) and mean difference=0.5+/-4.5 (95% confidence interval -8.3 to 9.3) mm Hg for the invasive model, and r=0.93 (P<0.001) and mean difference=-0.1+/-7.6 (95% confidence interval -15.0 to 14.8) mm Hg for the noninvasive model. Thus, our results indicate that central aortic systolic blood pressure could be estimated by analysis of the noninvasive brachial pressure wave alone from an oscillometric blood pressure monitor.

A double blind randomized trial to compare the effects of eprosartan and enalapril on blood pressure, platelets, and endothelium function in patients with essential hypertension.

The renin-angiotensin system is the major contributor to development of hypertension, atherosclerosis, and many other cardiovascular diseases. Angiotensin II, one of the main effectors of this system, contributes to the pathogenesis of hypertension and plays an important role in monocyte, platelet, and endothelium interactions. The effects on platelet and endothelial function, either by angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, are still not well understood. A double-blind, randomized, prospective trial of either enalapril (10-20 mg daily) or eprosartan (400-800 mg daily) over a 10-week period was conducted in 42 patients (27 males, 15 females). Platelet activation was evaluated by measuring platelet factor 4 (PF-4), beta-thromboglobulin (beta-TG), the ratio of platelet factor 4 to beta-thromboglobulin, and endothelial function by measuring total plasma nitrate levels, von Willebrand factor (vWF) levels, and blood flow using venous occlusive plethysmography. After a 10-week treatment with enalapril or eprosartan, the sitting blood pressure in both the enalapril group (from 152.2 +/- 18.7 mmHg to 141.9 +/- 23.5 mmHg, P < 0.05) and eprosartan group (from 151 +/- 10.0 mmHg to 142.3 +/- 12.9 mmHg, P < 0.05) was significantly reduced. Significant diastolic blood pressure (DPB) reduction (from 94 +/- 8.7 to 84.5 +/- 9.6 mmHg, P < 0.05) and a greater DBP reduction response were found in the eprosartan group (63% in eprosartan versus 25% in enalapril). Additionally, dose-dependent reductions in the indices of platelet activation and endothelial dysfunction were observed in patients administered high dose treatments of eprosartan and enalapril, and the beneficial effects of these agents were not correlated with the reduction of blood pressure using both agents. Eprosartan is effective and well-tolerated in the treatment of mid-to-moderate hypertension, and the DBP response reduction to eprosartin was better than that to enalapril. A high dose of either eprosartan or enalapril significantly decreased the indices of platelet activation and endothelial dysfunction in hypertensive patients. The benefits of both agents cannot be explained solely by their antihypertensive effects and possibly may be mediated through their unique effect on angiotensin blockade.

Prolongation of cardiac repolarization by arsenic trioxide.

Arsenic trioxide (As(2)O(3); ATO) has recently been found to be very effective for relapsed acute promyelocytic leukemia. Several articles reported prolongation of QT interval or ventricular arrhythmias in patients receiving ATO. However, the QT-prolonging effect has not been confirmed and the direct membrane effect of ATO has never been studied. In the present investigation, using conventional action potential recording technique, we found that ATO dose dependently prolonged action potential duration (APD) in guinea pig papillary muscle with a slow pacing frequency. Parenteral administration of ATO prolonged QT interval and APD in guinea pig hearts. Intravenous infusion of clinically relevant doses of ATO prolonged QT interval and APD dose dependently. These studies suggest that ATO has a direct effect on cardiac repolarization. Patients who are receiving ATO should avoid concomitant administration of other QT-prolonging agents or conditions in favor of delaying cardiac repolarization.

Genistein and tyrphostin AG 556 block the action potential shortening in septic shock.

BACKGROUND: We have previously shown that an increase in NO activity activated ATP-sensitive potassium channel (K(ATP)) and shortened action potential duration (APD) in an endotoxic shock model. Because the increase in NO production and the decrease of APD appear to be downstream late events in endotoxic shock, we hypothesized that a common signaling pathway might mediate these effects. METHODS: Using a guinea pig model of endotoxic shock, we investigated the effect of genistein and tyrphostin AG 556 on the cardiac action potential. Adult Hartley guinea pigs (300 to 450 gm) were randomized into 2 treatment parts. In the chronic treatment part, guinea pigs were randomized to receive daily subcutaneous injection of one of the five agents: saline, genistein, tyrphostin AG 556, daidzein, and vehicle for 10 days. In the acute treatment part, these agents were administered by intraperitoneal injection 1 hour before endotoxic shock. The animals were then anesthetized and mechanically ventilated, and underwent 6-hour endotoxic shock or sham experiment. RESULTS: In the chronic treatment part, the plasma nitrate concentration, myocardial guanosine 3',5'-cyclic monophosphate (cGMP) content, and APD at 90% repolarization (APD90) of papillary muscle showed no difference in the five groups before endotoxic shock. After 6-hour endotoxic shock, the elevation of plasma nitrate concentration and myocardial cGMP content was found significant in the control, the daidzein, and the vehicle groups, but was blunted in the genistein and the tyrphostin groups. The shortening of APD90 of papillary muscle was also significant in the control, the daidzein, and the vehicle groups, but blunted in the genistein and tyrphostin groups. There were similar findings in the acute treatment part, except the weaker effect of genistein and tyrphostin. CONCLUSIONS: Genistein and tyrphostin AG 556, either administered chronically or acutely, significantly attenuate the cardiac APD shortening in endotoxic shock, presumably through the decrease in the plasma nitrate and the cardiac cGMP production. It is suggested that tyrosine kinase signaling plays an important role in the modulation of APD in endotoxic shock.

Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes.

Genistein is an isoflavone with potent inhibitory activity on protein tyrosine kinase. Previous studies have shown that genistein has additional effects, among which the direct blocking effects on various ionic channels have recently been disclosed. Using whole-cell voltage clamp and current clamp techniques, we demonstrate that micromolar concentrations of genistein dose-dependently and reversibly inhibit the inward rectifying K(+) current, and depolarize the resting membrane potential, resulting in abnormal automaticity in guinea pig ventricular myocytes. Interestingly, another potent tyrosine kinase inhibitor, tyrphostin 51, did not produce the same inhibitory effect, while the inactive analogue of genistein, daidzein, had a similar blocking effect. We suggest that genistein directly blocks the inward rectifying K(+) current in ventricular myocytes, and one should be cautious of its pro-arrhythmic effect in clinical use.

The assessment of fluid status in haemodialysis patients: usefulness of the Doppler echocardiographic parameters.

BACKGROUND: In end-stage renal disease (ESRD) patients undergoing regular haemodialysis (HD), the maintenance of fluid status within an optimal range is critical. We therefore examined the role of Doppler echocardiographic parameters in the assessment of fluid status in these patients. METHODS: Three study groups were enrolled: 40 healthy volunteers (NTNR), 40 HD patients who were normotensive without receiving antihypertensive agents (NTHD) and 38 HD patients who had remained hypertensive (HTHD) despite antihypertensive treatment. Measurements of Doppler echocardiographic parameters from pulmonary vein (PV) and mitral inflow (Mi) were performed on a non-dialysis day. Extracellular water as a percentage of body weight (ECW%) and pre-dialysis mean blood pressure (BDMBP) were references for fluid status. The best Doppler parameter for fluid status assessment identified from the study groups was then tested in another validation groups (38 NTHD and 38 HTHD). RESULTS: Among all of the PV and Mi parameters, the S/D ratio (peak systolic velocity divided by peak diastolic velocity) was correlated with fluid status parameters best (with ECW%, r = -0.49, P<0.001; with BDMBP, r = -0.51, P<0.001). The correlations were independent of age, sex and Mi parameters. The receiver operating characteristics curve analysis demonstrated that an S/D ratio >1.33 had a sensitivity of 90% and a specificity of 77% in identifying NTHD patients. When the same criterion was applied to the validation groups, the positive predictive value was 64% and the negative predictive value was 86%. CONCLUSION: The Doppler-derived S/D ratio is a potentially useful marker for the assessment of fluid status in HD patients.

Estimation of preload recruitable stroke work relationship by a single-beat technique in humans.

The slope of the preload recruitable stroke work relationship (M(w)) is a highly linear, load-insensitive contractile index. To investigate whether M(w) can be determined from a single steady-state beat, 45 patients were studied during cardiac catheterization. Single-beat M(w) (SBM(w)) was calculated directly from the baseline stroke work and baseline left ventricular (LV) end-diastolic volume (EDV(B)), and the volume-axis intercept (V(w)) was estimated as k x EDV(B) + (k - 1) x LV(wall), where k is the ratio of the epicardial shell volumes corresponding to V(w) and EDV(B) and LV(wall) is the wall volume. The mean of individual k values was 0.72 +/- 0.04, which correlated with LV mass significantly (r = 0.60, P < 0.001). SBM(w) calculated from a constant k of 0.7 predicted M(w) well (r = 0.88, P < 0.0001), and the prediction improved slightly when k was estimated from individual LV mass (r = 0.93, P < 0.0001). Subgroup analyses revealed that the single-beat technique also worked in patients with small or large LV mass or volume or with regional wall motion abnormalities. The absolute change in SBM(w) after dobutamine infusion also correlated with that in M(w). In conclusion, M(w) can be estimated from a steady-state beat without alteration of preload.

Impact of left ventricular function on the pulmonary vein Doppler spectrum: nonsimultaneous assessment with load-insensitive indices.

Pulmonary vein Doppler spectrum is highly load-dependent and thus has been used to estimate left ventricular (LV) filling pressure. However, the impact of LV function on pulmonary vein Doppler spectrum remains obscure because only load-sensitive indices were studied previously. In the present study, measurements of the pulmonary vein Doppler spectrum were correlated with load-insensitive LV systolic (end-systolic elastance [Ees]) and diastolic (relaxation time constant [tau] and beta coefficient of the end-diastolic pressure volume relationship) function indices obtained from an invasive catheterization study nonsimultaneously. The peak velocity, velocity time integral, and duration of systolic forward spectrum were significantly correlated with Ees (r = 0.35, r = 0.36, and r = 0.41, respectively;P < 0.05). The pulmonary vein diastolic velocity time integral (PVDVTI) and duration of the diastolic forward spectrum were significantly correlated with Ees (r = 0.51 and r = 0.57, respectively;P < 0.01). PVDVTI was correlated with tau and the end-diastolic pressure-volume relationship (EDPVR) (r = 0.42 and r = 0.40 respectively,P < 0.05). On the other hand, the systolic fraction of the forward spectrum was significantly correlated with ejection fraction (for peak velocity,r = 0.63, P < 0.01; for velocity time integral,r = 0.37, P < 0.05) but not with Ees, and the diastolic fraction of the forward spectrum was significantly correlated with minimum pressure derivative over time (for peak velocity,r = 0.48, P < 0.05; for velocity time integral,r = 0.44, P < 0.05, respectively) but not with tau or EDPVR. In summary, the systolic and diastolic components of the pulmonary vein Doppler spectrum are affected variably by LV systolic and diastolic function, independent of the loading condition. The systolic and diastolic fraction of pulmonary vein Doppler spectrum appears to depend more on the loading condition than the LV systolic or diastolic function.

Left ventricular mass and hemodynamic overload in normotensive hemodialysis patients.

BACKGROUND: It remains uncertain whether the hemodynamic parameters are important determinants of left ventricular mass (LVM) in normotensive chronic hemodialysis (NTHD) patients, as has been found in their hypertensive counterparts. METHODS: Forty NTHD patients (mean age, 53.7 +/- 14.4 years; male/female, 18/22) without the requirement of antihypertensive drugs for at least six months were studied. Controls were 41 hypertensive hemodialysis patients (HTHD) and 46 normotensive subjects with normal renal function (NTNR). The influence of anthropometrics, cardiovascular structure and function, and volume status on LVM (by two-dimensional echocardiography) was analyzed by steps of multiple linear regression. RESULTS: As compared with the NTNR and NTHD group, the HTHD group had obvious pressure and volume/flow overload, and greater LV wall thickness, chamber size and mass. In contrast, NTHD subjects had similar blood pressure, large artery function, LV chamber size and stroke volume as the NTNR subjects. However, the NTHD patients still had greater wall thickness and LVM, along with greater cardiac output, lower total peripheral resistance and lower end-systolic meridional stress to volume ratio (ESSV) than the NTNR group. LVM in the NTHD group was significantly positively related to averaged systolic blood pressure (SBPavg), body surface area, extracellular fluid (ECF), carotid intima-media thickness (IMT), aortic pulse wave velocity (PWV), and negatively related to ESSV and Kt/V. The independent significant noncardiac structural determinants of LVM in NTHD subjects were ESSV, SBPavg, PWV and SV (model r2 = 0.617, P < 0.001). CONCLUSIONS: The NTHD patients, without significant pressure and volume overload, still had increased LVM that was partially explained by the persistent flow overload and subclinical LV dysfunction.

Clinical and angiographic determinants of adverse cardiac events in patients with stent restenosis.

Patients with angiographically proven stent restenoses do not necessarily develop adverse cardiac events. Which clinical, procedural, or angiographic parameters relate to the development of adverse cardiac events among these patients has not been determined. This study included 155 patients (167 stented lesions) with angiographically proven restenosis (> or = 50% diameter stenosis) within the stent or at its margins in routine follow-up angiograms that was obtained at 6.5 +/- 3.6 months after successful stenting. Thirty-six patients (22%) had adverse cardiac events (including unstable angina necessitating target lesion revascularization, acute myocardial infarction, or cardiac death) during follow-up and 119 patients (78%) were event-free. These two groups of patients were compared to determine the parameters related to adverse cardiac events. Univariate determinants of adverse events included hypertension (P = 0.023), unstable angina at initial presentation (P = 0.002), target lesion in proximal left anterior descending artery (P = 0.041), TIMI grade 0-2 flow in follow-up angiograms (p < 0.001), impaired left ventricular function at follow-up (P = 0.002), follow-up minimal lumen diameter < or = 0.6 mm (P = 0.003), follow-up diameter stenosis > 75% (P = 0.005), late loss > 2 mm (P = 0.01), and loss index > 1.127 (P < 0.001). Multivariate analysis demonstrated hypertension (odds ratio, OR, = 3.6; P = 0.019), unstable angina at initial presentation (OR = 2.6; P = 0.007), TIMI grade 0-2 flow at follow-up (OR = 2.8; P = 0.05), impaired LV function at follow-up (OR = 4.2; P = 0.004), and loss index > 1.127 (OR = 3.6; P = 0.017) as independent risk factors for adverse cardiac events. Classification and regression tree analysis identified loss index > 1.127 and impaired LV function as the two strongest determinant of adverse cardiac event. Therefore, hypertensive patients whose initial clinical presentation were unstable angina should be managed carefully to optimize the angiographic results and, most importantly, followed up more closely for development of impaired LV function after coronary stenting in order to prevent the occurrence of adverse cardiac event at follow-up.

Assessment of left ventricular end-systolic elastance from aortic pressure-left ventricular volume relations.

The left ventricular (LV) end-systolic pressure-volume relation (ESPVR) is a load-insensitive method for evaluating LV contractility, which needs invasive measurement. Some noninvasive methods substitute peak aortic pressure (Ps) for end-systolic LV pressure by assuming there is no difference between these pressures. However, this assumption has not been directly validated. With conductance catheter and dual micromanometers, ESPVRs and the slope (EesLv) were constructed from simultaneous LV pressures (LVP) and volumes, aortic pressures (AOP) and LV volumes (Ees(AO)), and Ps and LV end-ejection volumes (VEE) (Ees(PP-EEV)) during preload reduction in 50 subjects. The ratio of steady-state P(s) over V(EE) (P(S)/V(EE)) was also checked. AOP and LVP displayed differences of 11 +/- 6 and -30 +/- 12 mm Hg at the onset and end-ejection, respectively, and -2 +/- 4 mm Hg at end-systole. Ees(AO) and Ees(LV) were nearly identical: Ees(AO) = 0.97 x Ees(LV) + 0.05, r2 = 0.99. Ees(PP-EEV) correlated with EesLV (EesPP-EEV = 0.57 x EesLV + 0.61, r2 = 0.46) but with much more scatter. Ps/V(EE) correlated worst with Ees(LV). Central AOP can be substituted for LVP to derive EesLV. Other estimation methods yield weaker and poor correlations to directly measured Ees.