Rethinking False Positive Exercise Electrocardiographic Stress Tests by Assessing Coronary Microvascular Function.

BACKGROUND: Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. OBJECTIVES: The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). METHODS: Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. RESULTS: A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. CONCLUSIONS: In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.

A calixarene-based ion-selective electrode for thallium(I) detection.

Three new calixarene Tl(+) ionophores have been utilized in Tl(+) ion-selective electrodes (ISEs) yielding Nernstian response in the concentration range of 10(-2)-10(-6)M TlNO3 with a non-optimized filling solution in a conventional liquid contact ISE configuration. The complex formation constants (logßIL) for two of the calixarene derivatives with thallium(I) (i.e. 6.44 and 5.85) were measured using the sandwich membrane technique, with the other ionophore immeasurable due to eventual precipitation of the ionophore during these long-term experiments. Furthermore, the unbiased selectivity coefficients for these ionophores displayed excellent selectivity against Zn(2+), Ca(2+), Ba(2+), Cu(2+), Cd(2+) and Al(3+) with moderate selectivity against Pb(2+), Li(+), Na(+), H(+), K(+), NH4(+) and Cs(+), noting that silver was the only significant interferent with these calixarene-based ionophores. When optimizing the filling solution in a liquid contact ISE, it was possible to achieve a lower limit of detection of approximately 8nM according to the IUPAC definition. Last, the new ionophores were also evaluated in four solid-contact (SC) designs leading to Nernstian response, with the best response noted with a SC electrode utilizing a gold substrate, a poly(3-octylthiophene) (POT) ion-to-electron transducer and a poly(methyl methacrylate)-poly(decyl methacrylate) (PMMA-PDMA) co-polymer membrane. This electrode exhibited a slope of 58.4mVdecade(-1) and a lower detection limit of 30.2nM. Due to the presence of an undesirable water layer and/or leaching of redox mediator from the graphite redox buffered SC, a coated wire electrode on gold and graphite redox buffered SC yielded grossly inferior detection limits against the polypyrrole/PVC SC and POT/PMMA-PDMA SC ISEs that did not display signs of a water layer or leaching of SC ingredients into the membrane.