Poor reliability of P-wave terminal force V1 in ischemic stroke.

INTRODUCTION: Several ECG markers are postulated to represent underlying atrial remodelling and have been associated with ischemic stroke. P-wave terminal force in lead V1 (PTFV1) is one such marker. We examined the factors that contribute to the reliability of PTFV1 and its association with ischemic stroke. MATERIAL AND METHODS: Four hundred and thirty-five patients that presented with an ischemic stroke or transient ischemic attack (TIA) were identified through a prospectively maintained multi-site institutional stroke database. Control group consisted of age matched patients without prior history of an ischemic stroke or TIA. All patients underwent a 12-lead ECG and 24-hour Holter monitoring during the study period to exclude atrial fibrillation. RESULTS: Morphology consistent with PTFV1 occurred commonly in both the stroke/TIA and control groups. There was no significant difference in the median PTFV1 value between the stroke 3.96 mV ms [Interquartile range (IQR) 2.78-5.58] and control 4.23 mV ms [IQR 2.91-5.57] groups. Measurements of PTFV1 demonstrated excellent intra-observer reliability on assessment of the same P-wave (Intra class correlation (ICC) 0.91, p < 0.001) with narrow limits of agreement 2.21 to -2.95 mV ms. A change in the P wave assessed led to a significant reduction in reliability (ICC 0.79, p < 0.001). Inter-observer, inter P-wave assessment demonstrated further reduction in reliability (ICC 0.68, p < 0.002) with wide limits of agreement 6.17 to -5.78 mV ms, indicating significant under and overestimation of PTFV1. CONCLUSION: The utility of PTFV1 as a clinical marker for ischemic stroke is limited by the reduction in reliability associated with inter-observer and inter P-wave measurements.

In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodelling.

1. Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2. Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3. The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-beta1 (TGF-beta1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8-15; P < 0.01) and 5.3-fold reduction (95% CI 1.8-7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-beta1 and AngII-induced increases in alpha(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4. Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins.

Physiologic determinants of endothelin concentrations in human saliva.

BACKGROUND: Salivary endothelin (ET) concentrations have been shown to correlate with disease severity in patients with chronic heart failure (CHF). We undertook the present study to evaluate the stability of salivary ET under different handling conditions to assess its suitability as a biochemical marker in screening, diagnosis, and management of CHF. METHODS: Saliva samples were collected from healthy individuals and/or CHF patients, subjected to different handling conditions, and then stored at -80 degrees C until assayed by an ELISA for ET. RESULTS: Salivary ET concentrations showed a time-dependent increase during storage at room temperature. After 72 h of incubation at room temperature, ET increased approximately 2.8-fold (P = 0.03). Simultaneously, salivary big ET showed a time-dependent 11.2-fold decrease (P <0.0001). This activity was blocked by an ET-converting enzyme (ECE) inhibitor, suggesting that these changes were attributable to ECE-dependent cleavage of endogenous big ET in saliva. Ex vivo conversion was also observed when samples were stored at 4 degrees C, but the magnitude of these changes was markedly smaller (P <0.0001). Posture also affected salivary ET concentrations in CHF patients. With a change from supine to seated rest, salivary ET concentrations increased 1.5- and 1.8-fold after 20 and 40 min, respectively (P = 0.01). With a return to supine rest, salivary ET concentrations returned to baseline concentrations (P = 0.008). CONCLUSIONS: These data suggest that saliva sampling and handling conditions could markedly affect measurement of salivary ET. In particular, care should be taken to minimize ECE-dependent enzymatic conversion of endogenous big ET in saliva.