Insulin resistance is increased by transdermal estrogen therapy in postmenopausal women with cardiac syndrome X.

Estrogen has been reported to have both short- and long-term effects on the cardiovascular system. However, it remains to be examined how short-term transdermal estrogen therapy (TET) affects insulin sensitivity (SI) in patients with cardiac syndrome X (CSX), who are characterized by elevated insulin resistance. SI was assessed in a randomized, double-blind, placebo-controlled crossover study by minimal model analysis in seven postmenopausal women with CSX treated by TET. SI decreased by 32 +/- 8.3%, from 5.94 +/- 1.14 at baseline to 3.61 +/- 0.40 [(10(-4) x min(-1))/(microU/ml)] during TET (p = 0.03). Time to the onset of symptoms increased from 414.2 +/- 51.0 s at baseline to 450.0 +/- 53.2 s (p = 0.04). We conclude that TET increases SI in postmenopausal women with CSX. This effect is unrelated to the beneficial anti-ischemic effects on exercise duration.

The grades of ischemia on the presenting electrocardiogram of patients with ST elevation acute myocardial infarction.

Patients with acute myocardial infarction who have terminal QRS distortion in addition to ST-segment elevation (grade III ischemia) on their presenting electrocardiogram have higher mortality and larger final infarct size than patients with ST-segment elevation without changes in the terminal portion of the QRS complex (grade II ischemia). This article discusses the data concerning the prognostic significance of the grades of ischemia on the presenting electrocardiogram and the possible underlying mechanism of terminal QRS distortion. Patients with grade III ischemia have more severe ischemia and faster progression of necrosis than patients with grade II ischemia. This might be related to less protection by "ischemic preconditioning" or presence of collateral circulation.

Value of the initial electrocardiogram in patients with inferior-wall acute myocardial infarction for prediction of multivessel coronary artery disease.

BACKGROUND: Patients with inferior-wall acute myocardial infarction (AMI) who have ST-segment depression in the left precordial leads (LSTD+) on the initial electrocardiogram were reported to have more diffuse coronary artery disease (CAD) than had those without this finding (LSTD-). This suggests that LSTD+ patients may need extensive revascularization interventions more often than do LSTD- patients. However, this has not yet been confirmed. OBJECTIVE: To compare the coronary angiographic findings and treatment strategies for patients with inferior-wall AMI according to the LSTD pattern. METHODS: The clinical outcomes and the angiographic findings for 238 consecutive patients aged < or = 75 years who had been admitted to our hospital between 1 February 1995 and 1 February 1997 with inferior-wall AMI were retrospectively analyzed. The patients were divided into two groups according to the pattern of precordial ST-segment depression: LSTD+, ST-segment depression in leads V4-V6; and LSTD-, absence of this finding. All patients were treated according to current practice guidelines including with thrombolysis and revascularization interventions. RESULTS: The final study population included 217 patients; 83 were LSTD+ and 134 were LSTD-. All underwent coronary angiography within 30 days of the infarction. Compared with LSTD- patients, LSTD+ patients tended to be older (mean age 62.7 +/- 11.7 versus 58.3 +/- 9.6 years, P = 0.004), and had higher incidences of hypertension (39.8 versus 24.6%, P = 0.019) previous myocardial infarction (45.8 versus 20.1%, P = 0.0001) and congestive heart failure (21.7 versus 3.7%, P = 0.00008). Three-vessel CAD was much more common, and single-vessel CAD much less common, in the LSTD+ than in LSTD- group (62.7 versus 13.4% and 8.4 versus 50.7%, P < 0.00001 for both). Coronary-artery-bypass surgery and multivessel percutaneous coronary interventions (PCI) were used in treating 65.1% of the LSTD+ versus only 6.0% of the LSTD- patients (P < 0.00001), whereas single-vessel PCI was used in treating 71.6% of the LSTD- patients versus only 24.1% of the LSTD+ patients (P < 0.00001). Thus, the LSTD- pattern predicted single-vessel disease and single-vessel PCI only, whereas the LSTD+ pattern was predictive of multivessel CAD and of use of coronary-artery-bypass surgery or multivessel PCI (predictive values of 94.0 and 65.1%, respectively). CONCLUSIONS: Among patients with inferior-wall AMI, left precordial ST-segment depression predicts a very high prevalence of multivessel CAD and use of extensive revascularization interventions. The absence of this finding predicts nondiffuse CAD and lack of a need for extensive revascularization.

Thrombolysis is an effective and safe therapy in stuck bileaflet mitral valves in the absence of high-risk thrombi.

OBJECTIVES: We sought to evaluate the effectiveness and safety of thrombolytic therapy in stuck mitral bileaflet heart valves in the absence of high-risk thrombi. BACKGROUND: Current recommendations for the thrombolytic treatment of stuck prosthetic mitral valves are partially based on older valve models and inclusion of patients in whom high-risk thrombi were either ignored or not sought for. The feasibility and safety of thrombolysis in bileaflet models may be affected by the predilection of thrombi to catch the leaflet hinge. METHODS: We studied 12 consecutive patients (men/women = 5/7, age 58.8 +/- 14.9 years) who experienced one or more episodes of stuck bileaflet mitral valve over a 33-month period and received thrombolytic therapy with streptokinase, urokinase or tissue-type plasminogen activator. Transesophageal echocardiography was performed in all patients. Patients with mobile or large (>5 mm) thrombi were excluded. Functional class at initial episode was I-II in 4 patients (33.3%) and III-IV in 8 patients (66.6%). RESULTS: Patients receiving thrombolytic therapy achieved an overall 83.3% freedom from a repeat operation or major complications (95% confidence interval 51.6-97.9%). Minor bleeding occurred in three patients (25%) and allergic reaction in one (8.3%). Transient vague neurologic complaints, without subjective findings, occurred in four patients (33.3%). Three patients had one or more relapses within 5.2 +/- 3.1 months from the previous episode, and readministration of thrombolytics was successful. CONCLUSIONS: In clinically stable patients with stuck bileaflet mitral valves and no high-risk thrombi, thrombolysis is highly successful and safe, both in the primary episode and in recurrence. The best thrombolytic regimen is yet to be established.

Relation between evolutionary ST segment and T-wave direction and electrocardiographic prediction of mycardial infarct size and left ventricular function among patients with anterior wall Q-wave acute myocardial infarction who received reperfusion therapy.

In the prethrombolytic era it was found that infarct size and left ventricular ejection fraction could be predicted using the Selvester QRS score. We evaluated whether infarct size and left ventricular ejection fraction could be predicted by the predischarge QRS score in patients who had received reperfusion therapy and whether considering the configuration of the ST segments and T waves would increase the accuracy of these predictions. We evaluated 51 patients with first anterior wall myocardial infarction who had received reperfusion therapy and predischarge resting technetium-99m-sestamibi scan. The electrocardiograms recorded on the same day of the scan were analyzed for the QRS score and were divided into 3 groups: A, isoelectric ST and negative T waves; B, ST elevation (> or =0.1 mV) and negative T waves; and C, ST elevation (> or =0.1 mV) and positive T waves. Groups A, B, and C included 12, 23, and 16 patients, respectively. The myocardial perfusion defect extent increased from groups A to C (median 21%, 37%, and 43.5% in groups A, B, and C, respectively; p = 0.023). Similarly, left ventricular ejection fraction decreased (44%, 38%, and 34%, respectively; p = 0.042) from groups A to C. Overall, the correlation between the QRS score and the myocardial perfusion defect extent (rho 0.249; p = 0.08) and ejection fraction (rho -0.229; p = 0.11) was poor. A statistically significant correlation between myocardial perfusion defect size and QRS score was found only in group A (rho 0.599, p = 0.04). Among patients with anterior myocardial infarction who received reperfusion therapy, the predischarge QRS score was predictive of infarct size only in those in whom ST elevation resolved completely. In patients with residual ST elevation there was no correlation between QRS score and infarct size.

Persistent ST segment depression in precordial leads V5-V6 after Q-wave anterior wall myocardial infarction is associated with restrictive physiology of the left ventricle.

OBJECTIVES: To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV). BACKGROUND: Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV. METHODS: We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9). RESULTS: Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04). CONCLUSIONS: Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.

Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency.

AIMS: To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. METHODS: Patients with congestive heart failure (CHF, NYHA Class II-IV) and chronic renal insufficiency (creatinine clearance

Acute myocardial infarction following sildenafil citrate (Viagra) intake in a nitrate-free patient.

Since its introduction to the market in March 1997, sildenafil acetate (Viagra) has been prescribed to 1.7 million people. Sixteen men who were taking the drug have died, 7 of them during or soon after sexual activity. Most of these data have been derived from the media and not from the scientific literature. There is a general impression that cardiovascular complications of sildenafil occur mainly when the drug is taken concomitantly with nitrates. We describe a 65-year-old man with known coronary artery disease who had an acute myocardial infarction shortly after taking sildenafil and engaging an sexual activity. The patient had not been using nitrates. We suggest that the emotional arousal induced by Viagra, followed by the heavy physical exertion during sexual activity, triggers plaque rupture that leads to acute myocardial infarction.

Effect of isosorbide-5-mononitrate on exercise performance and clinical status in patients with congestive heart failure. Results of the Nitrates in Congestive Heart Failure (NICE) Study.

BACKGROUND AND AIMS: Nitrate therapy improves hemodynamics in patients with heart failure, but the chronic effects of oral nitrates on exercise performance and clinical status have not been well studied. METHODS: Oral isosorbide-5-mononitrate (ISMN) (50 mg once daily) or placebo was administered to 136 patients (NYHA Class 2-3) treated for heart failure, all receiving captopril and most also furosemide. Endpoints were treadmill exercise time at 12 weeks by modified Naughton protocol (primary), with an additional 12-week follow-up period. Secondary endpoints included left ventricular dimensions, ejection fraction, cardiothoracic ratio, functional class, quality of life, hospitalizations and plasma norepinephrine and atrial natriuretic peptide in a four-center substudy. RESULTS: Intention-to-treat analysis showed that mean change in treadmill exercise duration tended to be greater in patients receiving ISMN than placebo (treatment difference +42 s, 95% CI -5, +90 s at 12 weeks and +21 s, 95% CI -25, +74 s after 24 weeks) (NS). Treatment difference was greater in the prespecified subgroup with ejection fraction 31-40% (+55 s, 95% CI -11, +136 s at 12 weeks and +65 s, 95% CI +3, +147 s) (p = 0.035) at 24 weeks. No deleterious effects (i.e. hypotension) were observed with ISMN, although headache was reported in 19% of the active treatment group (p = 0.0001). CONCLUSIONS: ISMN added to captopril increased treadmill exercise time in patients with heart failure and a lesser reduction in baseline ejection fraction, although for the group as a whole, the increase in treadmill time was not significant.

Electrocardiographic criteria for predicting the culprit artery in inferior wall acute myocardial infarction.

Two patterns of the QRS complex in the lateral lead aVL on the admission electrocardiograms of patients with inferior wall acute myocardial infarction (AMI) were correlated with the culprit artery. S/R wave ratio < or =1/3 with ST depression < or =1 mm was found to be a sensitive and specific marker for left circumflex artery AMI, whereas S/R-wave ratio >1/3 with ST-segment depression >1 mm was suggestive of right coronary artery AMI.

Correlation of angiographic findings and right (V1 to V3) versus left (V4 to V6) precordial ST-segment depression in inferior wall acute myocardial infarction.

This study assessed whether differences in the underlying mechanisms for various patterns of precordial ST-segment depression with inferior acute myocardial infarction (AMI) are associated with poorer prognoses. We studied 1,155 patients with inferior AMI who underwent thrombolysis in the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO-I) angiographic substudy: those without precordial ST depression (n = 412; 35.7%), those with maximum ST depression in leads V1 to V3 (n = 547; 47.4%), and those with maximum ST depression in leads V4 to V6 (n = 196; 17.0%) on admission electrocardiogram. We compared the infarct-related artery, presence of left anterior descending or multivessel coronary artery disease, and left ventricular function among groups. Patients with maximum ST depression in leads V4 to V6 more often had 3-vessel disease (26.0%) than those without precordial ST depression (13.5%) or those with ST depression in leads V1 to V3 (15.7%; p = 0.002), and they had a lower ejection fraction (median 54% vs 60% and 55%, respectively; p <0.001). Patients with maximum ST depression in leads V1 to V3 less often had AMIs due to proximal right coronary artery obstruction (23.9%) than patients without precordial ST depression (35.2%) or those with ST depression in leads V4 to V6 (40.0%; p = 0.001) and had larger AMIs as estimated by peak creatine kinase. Different patterns of precordial ST depression are associated with distinctive coronary anatomy. ST depression in leads V4 to V6, but not V1 to V3, confers a greater likelihood of multivessel coronary artery disease.

Usefulness of dobutamine radionuclide ventriculography for prediction of left ventricular function improvement after coronary artery bypass grafting for ischemic cardiomyopathy.

Ventricular function may improve after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy depending on the amount of contractile myocardial reserve. Based on the studies using dobutamine echocardiography to predict regional wall improvement after revascularization, we investigated the benefit of low-dose dobutamine radionuclide ventriculography for assessing functional contractile reserve in this population. The study group included 56 patients with ischemic cardiomyopathy (mean left ventricular [LV] ejection fraction [EF] of 23 +/- 5%) and multivessel disease, who were referred for viability assessment. All underwent radionuclide ventriculography before and during infusion of 5 and 10 microg/kg/min of dobutamine. An increase in global LVEF from rest to dobutamine was calculated, and 10% was considered the cutoff value to predict ventricular improvement after CABG. Of the 35 patients who underwent CABG 1 month later, 29 were available for repeated radionuclide ventriculography after 12 +/- 5 months. Of these, 15 showed improvement (delta LVEF > or = 5%, mean 10 +/- 5%) and 14 did not (delta LVEF < 5%, mean -1 +/- 3%). The increase in EF with dobutamine had the highest univariate predictive value of all parameters evaluated. The sensitivity, specificity, and positive and negative predictive values of dobutamine radionuclide ventriculography were 67%, 93%, 91%, and 72%, respectively. We conclude that dobutamine radionuclide ventriculography is a useful method to assess contractile reserve and predict ventricular functional improvement after CABG in patients with ischemic cardiomyopathy.

Relation between QT dispersion and slow intraventricular conduction in patients with acute anterior wall myocardial infarction.

BACKGROUND: QT dispersion has been proposed as a simple, noninvasive measure for identifying patients at risk of postinfarction arrhythmia. It is assumed to reflect nonuniform ventricular repolarization, which, in turn, may result from regional differences in repolarization time as well as from localized activation delay. The aim of this study was to examine the relation between QT dispersion and intraventricular conduction abnormalities in patients with acute anterior wall myocardial infarction. METHODS AND RESULTS: Standard 12-lead electrocardiographic and 12-lead signal-averaged electrocardiographic recordings were performed in 25 patients with a first Q-wave anterior wall myocardial infarction. Measures calculated by using the 6 precordial (V1 through V6) leads for QT dispersion were (1) difference between maximum and minimum QT and QTc intervals and (2) standard deviation of QT and QTc intervals. Measures calculated from the signal-averaged electrocardiogram were (1) maximum filtered QRS duration; (2) mean; and (3) standard deviation of filtered QRS duration. No relation was found between any measure of filtered QRS duration and that of QT dispersion by using linear correlation analysis. Similarly, no significant association was demonstrated between the filtered QRS duration and corresponding QT interval measurements (total 131 leads). CONCLUSIONS: The lack of correlation between signal-averaged electrocardiogram indexes of slow intraventricular conduction and electrocardiogram variables of QT dispersion suggests an independent predictive value for the 2 methods in identifying patients at risk of postinfarction arrhythmia. This suggestion is further supported by the finding that altered activation sequence is an unlikely mechanism of QT dispersion in patients with acute myocardial infarction, as indicated by the lack of association between the filtered QRS duration and corresponding QT interval measurements.

The prognostic implications of negative T waves in the leads with ST segment elevation on admission in acute myocardial infarction.

We assessed the prognostic significance of negative T waves on admission in leads with ST elevation in 2,853 patients with acute myocardial infarction treated with thrombolysis. Patients were classified into 2 groups based on the presence of negative (T-) or positive (T+) T waves in the leads with ST elevation on admission. T+ and T- waves on admission were detected in 2,601 (91%) and 252 (9%) patients, respectively. T- waves were observed in 6.7 and 9.6% of patients admitted 2 h after symptom onset. T- patients admitted 2 h after onset suffered higher mortality (20/196 patients; 10.2%) than T+ patients (100/1,836 patients; 5.4%; p = 0.01). Multivariate analysis of the data on patients treated >2 h after onset demonstrated T- waves to be associated with mortality (OR 1.86; 95% CI 1.07-3.25; p = 0.017). T- waves in leads with ST elevation upon admission are associated with adverse prognosis in patients presenting >2 h after symptom onset, whereas in patients presenting

Value of T-wave direction with lead III ST-segment depression in acute anterior wall myocardial infarction: electrocardiographic prediction of a "wrapped" left anterior descending artery.

BACKGROUND: Lead III ST-segment depression during acute anterior wall myocardial infarction (AMI) has been attributed to reciprocal changes. However, the value of the T-wave direction (positive or negative) in predicting the site of obstruction and type of the left anterior descending (LAD) artery is not clear and has not been studied before. HYPOTHESIS: The aim of the study was to assess retrospectively the correlation between two patterns of lead III ST-segment depression, and type of LAD artery and its level of obstruction during first AMI. METHODS: The study group consisted of 48 consecutive patients, admitted to the coronary care unit for first AMI, who showed ST-segment elevation in lead a VL and ST-segment depression in lead III on admission 12-lead electrocardiogram. The patients were divided by T-wave direction into Group 1 (n = 31), negative T wave, and Group 2 (n = 17), positive T wave. The coronary angiogram was evaluated for type of LAD ("wrapped", i.e., surrounding the apex or not), site of obstruction (pre- or postdiagonal branch), and other significant coronary artery obstructions. RESULTS: Mean lead III ST-segment depression was 1.99 +/- 1.32 mm in Group 1 and 1.13 +/- 0.74 mm in Group 2 (p = 0.004); mean ST-segment elevation in a VL was 1.35 +/- 0.84 mm and 1.23 +/- 0.5 mm, respectively (p = 0.5). A wrapped LAD was found in 12 patients (38.7%) in Group 1 and in 13 in Group 2 (76.4%) (p = 0.02). The sensitivity of lead III ST-segment depression with positive T wave to predict a wrapped LAD was 52%, and the specificity was 82% with a positive predictive value of 76%. On angiography, 25 patients (80%) in Group 1 and 13 (76%) in Group 2 had prediagonal occlusion of the LAD (p = 0.77). No significant difference between groups was found for right and circumflex coronary artery involvement or incidence of multivessel disease. CONCLUSIONS: The presence of lead III ST-segment depression with positive T wave associated with ST-segment elevation in a VL in the early course of AMI can serve as an early electrocardiographic marker of prediagonal occlusion of a "wrapped" LAD.

Coronary stent deployment without predilation: prevention of complications of venous graft angioplasty.

Saphenous vein graft stenting without predilation may potentially decrease procedural complications such as distal embolization and no-reflow phenomenon. In this report the authors describe the deployment of stents (three Wallstents, one Palmaz-Schatz, one Multilink, and one NIR) without predilation in five patients with unstable angina pectoris due to high-grade stenosis in old saphenous vein grafts. Stent deployment was successful in all patients without procedure-related complications. Stenting without predilation appears to be feasible in old bypass grafts with significant stenosis. The potential of this new stenting technique to reduce the risk of stenting complications should be tested by a randomized trial.

QRS complex distortion predicts no reflow after emergency angioplasty in patients with anterior wall acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction, distortion of the terminal portion of the QRS complex on the electrocardiogram (ECG) at the time of their admission to hospital is associated with larger final infarct size and greater mortality. This study assessed the results of emergency coronary angioplasty in patients with anterior acute myocardial infarction with and without distortion of the terminal portion of the QRS complex on the admission ECG. METHODS: We assessed the Thrombolysis in Myocardial Infarction (TIMI) trial flow grade, resolution of ischemic ECG changes, and clinical outcome after emergency angioplasty for acute anterior wall myocardial infarction in patients with (n = 21) and without (n = 21) distortion of the terminal portion of the QRS complex on the admission ECG. RESULTS: Compared with patients without distortion of the terminal portion of the QRS complex on the admission ECG, those with distortion had a significantly lower incidence of TIMI flow grade 3 (52% compared with 84%, P < 0.05), lower rate of resolution of the ischemic ECG changes (33% compared with 84%, P < 0.005), and greater rate of mortality during their stay in hospital despite successful balloon angioplasty (19% compared with 0%, P < 0.05). CONCLUSIONS: In patients with anterior wall acute myocardial infarction, distortion of the terminal portion of the QRS complex on the admission ECG predicts a greater mortality rate and a greater incidence of reflow impairment after emergency angioplasty.

Acute anterior wall myocardial infarction entailing ST-segment elevation in lead V1: electrocardiographic and angiographic correlations.

BACKGROUND: The correlation between ST elevation in lead V1 during anterior wall acute myocardial infarction (AMI) and the culprit lesion site in the left anterior descending (LAD) coronary artery is poor. HYPOTHESIS: The study was undertaken to assess the electrocardiographic (ECG) characteristics and angiographic significance of ST-segment elevation in lead V1 during anterior wall acute myocardial infarction (AMI). METHODS: Data from 115 patients with anterior wall AMI, who underwent coronary angiography within 14 days of hospitalization, were studied. The admission 12-lead ECG was examined and the coronary angiogram was evaluated for the nature of the conal branch of the right coronary artery (RCA) and for the culprit lesion site in the left anterior descending (LAD) coronary artery. RESULTS: Mean ST-segment deviation and the frequency of patients with ST-segment elevation > 0.1 mV were significantly lower in lead V1 than in lead V2 (0.136 +/- 0.111 mV vs. 0.421 +/- 0.260 mV, and 37 vs. 96%, for leads V1 and V2, respectively). A small conal branch not reaching the interventricular septum (IVS) was more prevalent among patients with ST-segment elevation > 0.1 mV in lead V1 (67%), whereas a large conal branch was more prevalent in patients with ST-segment deviation (1 mV in that lead (83%, p < 0.001). No relation was found between ST-segment deviation in lead V1 during anterior wall AMI and the culprit lesion site in the LAD. CONCLUSION: ST-segment elevation in lead V1 during first anterior wall AMI was found in one third of the patients, and its magnitude was lower than that in the other precordial leads. ST-segment elevation in lead V1 favors the presence of a small conal branch of the RCA that does not reach the IVS.