Assessment of Intracoronary Adenosine-Induced Hyperemia in Patients with Atrial Fibrillation in Comparison with Patients in Sinus Rhythm.

BACKGROUND: Fractional flow reserve (FFR) is routinely used to evaluate coronary stenosis in patients with atrial fibrillation (AF), although no studies currently address its reliability in this particular population. The clinical impact of correct assessment of coronary stenosis in AF is particularly high in light of the antithrombotic therapy imposed by both AF and coronary stenting. OBJECTIVES: Given the hemodynamic variability and microvascular dysfunction described in AF, the aim of this study was to evaluate the hyperemic response to intracoronary adenosine in AF in comparison with sinus rhythm (SR). METHODS AND RESULTS: This retrospective study included 36 patients in AF and 36 patients in SR. The hyperemic curves were derived in a subset of patients where the required information was available (n = 16 AF, n = 10 SR). AF patients presented a hyperemic response after intracoronary administration of adenosine, which was equivalent to SR in terms of magnitude and time to maximal hyperemia. CONCLUSION: There is equivalent hyperemic response in FFR-guided revascularization in AF versus SR population. Our findings support the use of FFR in evaluating intermediate coronary stenosis in AF.

Comparison of efficacy and safety of intracoronary nicardipine and adenosine for fractional flow reserve assessment of coronary stenosis.

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.

Adenosine intracoronary bolus dose escalation versus intravenous infusion to induce maximum coronary hyperemia for fractional flow reserve assessment.

BACKGROUND: Achievement of maximal hyperemia is mandatory for an accurate calculation of fractional flow reserve (FFR) and it is obtained with adenosine given either as an intravenous infusion or as an intracoronary bolus. AIMS: The purpose of this study was to compare the infusion of adenosine with intracoronary adenosine bolus dose escalation in the optimal assessment of peak FFR. METHODS: We enrolled consecutive patients with borderline coronary lesions that were assessed by FFR with the use of adenosine intracoronary boluses (100, 200, 400 and 600 µg) and intravenous infusion of 140 µg/kg/min and 280 µg/kg/min. FFR values were assessed and compared. RESULTS: Fifty patients with 125 borderline coronary artery stenoses were enrolled. Physiological severity assessed with: intravenous adenosine infusion at 140 µg/kg/min was mean 0.82 ± 0.09; infusion at 280 µg/kg/min - 0.81 ± 0.09; intracoronary bolus of 100 µg, 200 µg, 400 µg and 600 µg - 0.83 ± 0.09; 0.83 ± 0.09, 0.83 ± 0.09; and 0.83 ± 0.09, respectively. There was a strong linear correlation between FFR values obtained from 140 µg/kg/min infusion and adenosine intracoronary 100, 200, 400 and 600 µg bolus injection (r = 0.989, r = 0.99, r = 0.993, r = 0.994, respectively, p < 0.001 for all). CONCLUSIONS: FFR values achieved with intracoronary boluses of adenosine are very similar, but not identical to those obtained using intravenous adenosine administration. The values of FFR may vary between escalating doses of intracoronary boluses and intravenous infusion.

Assessment of endothelial function during the loading phase of infliximab in psoriasis: a potential predictor of its drug survival.

BACKGROUND: Tumor necrosis factor inhibitors decrease the risk of cardiovascular events in moderate to severe psoriasis, but the association between their effects on endothelial function and those on skin lesions has not been well studied. We investigated the association between infliximab effects on endothelial function during the loading phase and those on skin lesions in patients with psoriasis. METHODS: We evaluated endothelial function with reactive hyperemia-peripheral arterial tonometry index (RHI) in 15 patients with psoriasis before the first and third infusions of infliximab. Patients were stratified into two groups; those who maintained Psoriasis Area and Severity Index (PASI) 75 response for more than 6 months (defined as responders) and the others (defined as nonresponders). RESULTS: Six weeks after the initiation of infliximab (before the third infusion), PASI scores were significantly improved compared with baseline, while RHI values were not altered in the whole patient group. However, when the responders and the nonresponders were analyzed separately, RHI values tended to be decreased before the third infusion compared with baseline in the nonresponders, while being unchanged in the responders. Importantly, the difference in ∆RHI reached a statistical significance between the two groups, and the cutoff value (mean - 2 standard deviation of RHI values in the responders) identified the nonresponders with 67% of sensitivity and 100% of specificity. CONCLUSIONS: The decrease in RHI values before the third infusion may serve as a predictor for the long-term unfavorable effect of infliximab on psoriatic skin lesions.

Impact of increasing dose of intracoronary adenosine on peak hyperemia duration during fractional flow reserve assessment.

BACKGROUND: Fractional Flow Reserve (FFR) is currently indicated as a first line strategy for the functional assessment of intermediate coronary stenoses. However, the protocol for inducing hyperemia still lacks standardization. Intracoronary adenosine boli, with a progressive increase to high-dosage, have been proposed as a sensitive and accurate strategy for the classification of coronary stenoses, although being potentially affected by the achievement of plateau of the effect and by a less prolonged and stable hyperemia as compared to intravenous administration. Therefore, the aim of the present study was to define the conditioning parameters and assess the impact of increasing-dose intracoronary adenosine on peak hyperemia duration in patients undergoing FFR for intermediate coronary stenoses. METHODS: FFR was assessed in patients with intermediate (40 to 70%) lesions by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Hyperemic duration was defined as the time for the variation form minimum FFR ±â€¯0.02 and time to recovery till baseline values. RESULTS: We included 87 patients, undergoing FFR evaluation of 101 lesions. Mean peak hyperemia duration and time to recovery significantly increased with adenosine doses escalation (p = 0.02 and p < 0.001). Peak hyperemia duration and time to recovery with 1440 µg adenosine were 14.5 ±â€¯12.6 s and 45.2 ±â€¯30.7 s, respectively. Hyperemia duration was not related to Quantitative Coronary Angiography (QCA) parameters or FFR values. In fact, a similar increase in the time of hyperemic peak was noted when comparing patients with positive or negative FFR (pbetween = 0.87) or patients with lesions < or ≥20 mm (pbetween = 0.92) and lesions involving left main coronary or proximal left anterior descending artery (LAD) (pbetween = 0.07). A linear relationship was observed between time to recovery and FFR variations, with a greater time to baseline required in patients with FFR ≤ 0.80 (p = 0.003) and in lesions ≥ 20 mm (p = 0.006), but not in LAD/LM lesions (p = 0.55). CONCLUSIONS: The present study shows a progressive raise in the duration of peak hyperemia and time to recovery, after the administration of increasing doses of intracoronary adenosine for the assessment of FFR. Therefore, considering the potential advantages of a high-dose adenosine protocol, allowing a more prolonged hyperemia and a more precise and reliable measurement of FFR, further larger studies with such FFR strategy should certainly be advocated to confirm its safety and benefits, before its routinely use recommendation.

Assessment of ocular redness measurements obtained with keratograph 5M and correlation with subjective grading scales.

OBJECTIVE: To examine correlations between ocular redness scores provided by the Keratograph 5M and those determined using two image-based grading scales. METHODS: Observational prospective cross-sectional study. Two hundred and twenty six eyes of two hundred and twenty six participants (175 patients using anti-glaucoma eye drops and 51 subjects untreated). All subjects were scored automatically using the keratograph 5M. These redness scores (RS) were then correlated with the gradings provided by the Efron and McMonnies/Chapman-Davies scale (MC-D) scales (two observers). RESULTS: Excellent reproducibility was observed for both the Efron (weighted K=0.897, 95% CI 0.823-0.904) and MC-D (weighted K=0.783, 95% CI 0.752-0.795) scales. Keratograph RS and the scores obtained with both Efron (Spearman's Rho=0.43, P<0.001) and MC-D (Spearman's Rho=0.48, P<0.001) scales were significantly correlated. RS for the bulbar and limbal - nasal and temporal quadrants also correlated moderately with the two subjective scales. Through Bland Altman analysis, poor agreement was detected between the objective and subjective methods: agreement values for the Efron scale or MC-D scale (matching scorers between observers) versus overall RS showed high biases (-15.58 and -22.05 respectively) and wide limits of agreement (LOA) (-46.169 to 15.005 and -52.534 to 8.19 respectively). Lowest bias was observed between temporal limbal RS and Observer 2 Efron score (-0.04). CONCLUSIONS: Although it emerged as a reliable objective method, the keratograph 5M overestimated the scores compared with the subjective grading scales when used to grade the degree of ocular redness. Therefore, they should not be interchangeable methods.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis in comparison with instantaneous wave-free ratio.

BACKGROUND: Despite evidence demonstrating the benefits of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to compare the diagnostic performances of instantaneous wave-free ratio (iFR) to a novel contrast medium-induced index in FFR prediction, hypothesizing that the latter parameter would offer superior diagnostic agreement with FFR. METHODS & RESULTS: We studied 132 intermediate stenoses in 97 patients prospectively. iFR was measured first, followed by intracoronary injection of 6 mL contrast medium at 3 mL/s to obtain end-diastolic instantaneous distal coronary pressure/aortic pressure ratio (Pd/Pa) 60 ms before the electrocardiographic R-wave (C-ED-Pd/Pa). Subsequently, conventional hyperemic FFR was measured as a reference standard. Of the 132 lesions, 120 were available for final analysis. The FFR values of 95/120 lesions (79.2%) were between 0.60 and 0.90. C-ED-Pd/Pa values (median 0.79 [interquartile range 0.69-0.87]) were significantly lower than FFR values (0.81 [0.75-0.88], P<0.01), whereas iFR values (0.91 [0.86-0.94], P<0.01) were significantly higher. Correlation coefficients with FFR were 0.78 (standard error of the estimate [SEE] 0.067, P<0.0001) and 0.93 (SEE 0.052, P<0.0001) for iFR and C-ED-Pd/Pa, respectively (P<0.001). The areas under the receiver operating characteristic curves were 0.88 and 0.96 for iFR and C-ED-Pd/Pa, respectively (P<0.01). Diagnostic accuracy was 85.0% and 92.5% for iFR and C-ED-Pd/Pa, respectively (P=0.06). CONCLUSIONS: C-ED-Pd/Pa is a novel, practical, and accurate measure for the physiological assessment of intermediate coronary stenosis compared to iFR.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis.

BACKGROUND: Despite evidence demonstrating the superiority of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to determine the diagnostic performance of baseline conditions and contrast medium-induced pressure indices in predicting FFR. We hypothesized that the contrast medium-induced end-diastolic pressure parameter would offer superior diagnostic agreement with FFR, compared to other indices. METHODS & RESULTS: Ninety-one intermediate stenoses in 75 patients were studied prospectively. The baseline distal coronary pressure to aortic pressure ratio (Pd/Pa) and end-diastolic instantaneous Pd/Pa 60 ms before the electrocardiographic R-wave (ED-Pd/Pa) were measured; then, after intracoronary injection of 6 mL contrast medium at 3 mL/s, Pd/Pa (C-Pd/Pa) and end-diastolic Pd/Pa (C-ED-Pd/Pa) were obtained. Subsequently, conventional FFR was measured as a reference standard. Of the 91 lesions, 11 (12.1%) were excluded because of suboptimal data acquisition, leaving 80 for final analysis. C-ED-Pd/Pa values (median 0.80 [interquartile range 0.70-0.88]) were significantly lower than conventional FFR (0.83 [0.75-0.89], P<0.01), whereas Pd/Pa (0.93 [0.90-0.96], P<0.01), ED-Pd/Pa (0.91 [0.87-0.93], P<0.01), and C-Pd/Pa (0.85 [0.79-0.90], P<0.05) were significantly higher. Correlation coefficients (R) with conventional FFR were 0.74 (standard error of the estimate [SEE] 0.067, P<0.0001), 0.78 (SEE 0.062, P<0.0001), 0.85 (SEE 0.052, P<0.0001), and 0.93 (SEE 0.037, P<0.0001) for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. Diagnostic accuracy was 81.2%, 83.8%, 87.5% and 93.8% for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. CONCLUSIONS: Among baseline indices and contrast-induced pressure parameters, C-ED-Pd/Pa is a novel, feasible, and high-performance measure for the physiological assessment of intermediate coronary stenosis.

Invasive assessment of the coronary microcirculation using the index of microcirculatory resistance: description and validation of an animal model.

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-µm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Nitroprusiato: una droga confiable para la estimación de la reserva de flujo fraccional coronario / Nitroprusside: a reliable drug for fractional flow reserve assessment

La angiografía coronaria permanece como "gold standard" para el diagnóstico y toma de decisiones en la enfermedad coronaria. Sin embargo, la significación de lesiones con estenosis de 50-70 por ciento es difícil. La medición de la reserva de flujo fraccional (FFR) es una herramienta útil para dilucidar esta interrogante. Generalmente se usa adenosina (A) en bolo intracoronario para inducir máxima vasodilatación y hay poca evidencia para drogas alternativas con este objeto. En este estudio evaluamos el uso de nitroprusiato (N) como droga alternativa. Métodos y Resultados: Se efectuó un estudio clínico aleatorizado. A (120 ug IC) y posteriormente N (50 ug IC), o vice-versa, se usaron para evaluar cada lesión. Se evaluaron 60 lesiones en 44 pacientes (24 hombres) de 63.5 +/- 9.6 años, con masa corporal 28.95 +/- 3.32 kg/m2. Las lesiones se localizaron en arteria descendente anterior en 46.7 por ciento, coronaria derecha en 26.7 por ciento, circunfleja en 11.7 por ciento y 13.9 por ciento en las otras arterias. La estenosis coronaria promedio evaluada por angiografía cuantitativa fue 49.5 por ciento (95 por ciento CI: 46.5 - 52.5 por ciento). La presión arterial media (PAM) basal fue similar en ambos grupos (pre - A: 106.5 +/- 18.2 mmHg, pre - N: 105.6 +/- 18.8 mmHg, NS) o después de A, pero se observó un descenso transitorio después de NP (descenso promedio de 12.5 mmHg, 95 por ciento CI: 9.2 a15.7 mmHg, 2p < 0.001). Este efecto estaba asociado a la hiperemia prolongada lograda con N. (duración de hiperemia con N: 39.2 +/- 8.7 s., y con A of 15.3 +/- 3.2 s. 2p < 0.001). Hubo excelente correlación entre los resultados de A y de N respecto de FFR (r 0.986)...

Abstract: Coronary angiography remains the gold standard for diagnosing coronary artery disease and making therapeutic decisions. However the significance of intermediate lesions (between 50-70%) is difficult to evaluate. Fractional flow reserve (FFR) measurement is an important tool for the evaluation of these lesions. To achieve maximum vasodilatation, Intracoronary (IC) bolus or a continuous intravenous infusion of (A) is usually used. There is very little data for an alternative drug. The aim of this study was to evaluate Sodium nitroprusside (N) 50 IC bolus as an alternative to A for to determine FFR.Method and Results: A multicentric, randomized clinical trial was conducted. A, (120 IC) and subsequently N (50 IC) or vice versa was used for every lesion. 60 coronary lesions were evaluated in 44 patients (24 men and 20 women), mean age 63.5 ± 9.6 years and BMI 28.95 ± 3.32 kg/m2. The lesions were located in the left anterior descending artery in 46.7% of patients, the right coronary in 26.7%, the circumflex in 11.7% and others in 13.9%. Mean coronary artery stenosis as assessed by quantitative coronary angiography (QCA) was 49.5% (95% CI: 46.5 - 52.5%).The mean arterial pressure (MAP) was similar in groups at baseline.(pre - A: 106.5 ± 18.2 mmHg, pre - N: 105.6 ± 18.8 mmHg, NS), or after A, but there was a transient decrease in MAP when N was administered (average decline of MAP: 12.5 mmHg, (95% CI: 9.2 to 15.7 mmHg, 2p < 0.001). This effect was due to the prolonged hypere-mia time achieved with the drug (hyperemia duration with nitroprusside 39.2 ± 8.7 sec. and with adenosine of 15.3 ± 3.2 sec. 2p < 0.001). We could demonstrate an excellent correlation between IC nitroprusside and IC adenosine with regard to FFR measurement, (correlation coefficient = 0.986, p < 0.001)...

Balancing efficacy and tolerability of prostaglandin analogues and prostaglandin-timolol fixed combinations in primary open-angle glaucoma.

BACKGROUND: Lowering intraocular pressure (IOP) is currently the only therapeutic approach that preserves visual function in primary open-angle glaucoma. In making treatment decisions for first- and second-line therapy, the clinician needs to provide an appropriate balance of efficacy and tolerability. Prostaglandin analogues (PGAs) are frequently used as first-line monotherapy, because of their efficacy and low risk of systemic side effects. Similarly, PGA-based fixed combinations are frequently used in patients who progress or fail to achieve the target IOP. SCOPE: We have reviewed the literature on the management of primary open-angle glaucoma with PGAs, both as monotherapies and in fixed combinations. FINDINGS: In the clinical trial and meta-analysis data identified, bimatoprost 0.03% seems to be associated with a greater overall ability to lower IOP compared with latanoprost, travoprost or tafluprost, at the cost of a slightly higher incidence of conjunctival hyperaemia. Studies indicate that patients' adherence to treatment is generally better with PGAs than with many other monotherapies. In patients requiring more than one IOP-lowering agent, fixed combination treatments may provide improved adherence and tolerability benefits compared with concomitant use of individual treatments. Bimatoprost/timolol fixed combination appears to be slightly more efficacious than latanoprost/timolol or travoprost/timolol, and tolerability differences between the fixed combinations appear to be slight, probably because the addition of timolol to the PGA component lessens the associated hyperaemia. Surveys on EU physician attitudes appear largely in line with these clinical data. CONCLUSION: An appropriate balance between efficacy and tolerability ensures optimum IOP lowering and reduces the risk of non-adherence. PGAs largely fulfil this need as monotherapies and as components of combinations.

Assessment of blood flow changes in human skin by microdialysis urea clearance.

OBJECTIVE: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin and compare it to two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging. METHODS: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine to induce local tissue hyperemia, hypoperfusion, and hyperemia, respectively. RESULTS: Urea clearance, but not the other techniques, detected the changes in blood flow during changes in flow. The last hyperemic response was detected by all three methods. CONCLUSION: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

Digital assessment of endothelial function and ischemic heart disease in women.

OBJECTIVES: We investigated the utility of digital reactive hyperemia peripheral arterial tonometry (RH-PAT) in predicting ischemic heart disease (IHD), including obstructive coronary artery disease (CAD) and nonobstructive coronary artery disease (NOCAD), in women. BACKGROUND: IHD is the leading cause of mortality, and its pathogenesis is diverse in women. Fingertip RH-PAT is a new device that provides noninvasive, automatic, and quantitative evaluation of endothelial dysfunction. METHODS: RH-PAT was measured using Endo-PAT2000 (Itamar Medical, Caesarea, Israel) before cardiac catheterization in 140 stable women scheduled for hospitalization to examine chest pain. NOCAD was diagnosed by angiography with measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation test and cardiac scintigraphy with stress tests. RESULTS: Sixty-eight women (49%) had obstructive CAD and 42 women (30%) had NOCAD. RH-PAT indexes were significantly attenuated in both obstructive CAD and NOCAD as compared with non-IHD (n = 30) (obstructive CAD: median 1.57, interquartile range [IQR] 1.42 to 1.76; NOCAD: median 1.58, IQR 1.41 to 1.78; non-IHD: median 2.15, IQR 1.85 to 2.48, p < 0.001). By multivariate logistic regression analysis, only RH-PAT index was significantly associated with IHD, including obstructive CAD and NOCAD (odds ratio 0.51; 95% confidence interval: 0.38 to 0.68; p < 0.001). In receiver-operating characteristic analysis, RH-PAT index was a significant predictor of IHD (area under the curve 0.86; p < 0.001). Furthermore, only RH-PAT was useful for the prediction of NOCAD after excluding obstructive CAD (area under the curve 0.85; p < 0.001; RH-PAT index of <1.82 had 81% sensitivity and 80% specificity). CONCLUSIONS: RH-PAT indexes were significantly attenuated in women with IHD. Digital RH-PAT can predict patients with IHD, especially NOCAD before angiography. RH-PAT is potentially useful for identifying high-risk women for IHD. (Endothelial Dysfunction and Coronary Artery Spasm; NCT00619294).

Hyperemia-associated costs of medication changes in glaucoma patients treated initially with prostaglandin analogs.

AIMS: To develop a model to estimate and compare the cost of changing therapy due to hyperemia in glaucoma patients treated initially either with latanoprost, bimatoprost, or travoprost monotherapy. METHODS: Data collected from the HealthCore Integrated Research Database, as part of the Glaucoma Adherence and Persistency Study (GAPS), were used to populate the model. Patients with a documented diagnosis of glaucoma who were newly treated (no ocular hypotensive medication and no glaucoma-related procedure during 6 months before first prescription) with latanoprost, bimatoprost, or travoprost monotherapy were identified. The time horizon for the base-case model was the duration of chart abstraction (mean = 4.1 years); a 3-month model also was developed. Physician-reported rates of hyperemia were obtained from chart reviews of 300 patients. Transition rates reflected events related to reports of hyperemia where a physician-driven change (switch or discontinuation) in therapy was documented. The per-patient direct cost (2008) due to hyperemia-driven change in therapy was calculated as the sum of the cost of the initial prescription plus the cost of the office visit where the patient was evaluated and the decision to change therapy was made. Costs were stratified by whether patients were hyperemia free or discontinued the initial therapy due to hyperemia. RESULTS: From the sample of 13,977 newly treated patients, 8,743 patients were started on a prostaglandin monotherapy only. Of these, 5,726 received latanoprost, 1,633 were treated with bimatoprost, and 1,384 received travoprost index monotherapy. Across all treatment groups, costs among hyperemia-free patients were US$73.67 versus US$140.02 for those who discontinued the initial prostaglandin due to hyperemia. Per-patient costs were lowest in the group treated initially with latanoprost. For the base-case model, with latanoprost as the reference, total per-patient incremental costs due to hyperemia-driven change in therapy were US$5.92 for bimatoprost and US$5.43 for travoprost. Results were not highly sensitive to increases either in the incidence of hyperemia among latanoprost-treated patients or in the cost of latanoprost. CONCLUSIONS: Hyperemia results in increased overall costs in patients treated with latanoprost, bimatoprost, and travoprost. Treatment with latanoprost is associated with lower hyperemia-related costs than treatment with bimatoprost or travoprost.

Usefulness of translesional pressure gradient and pharmacological provocation for the assessment of intermediate renal artery disease.

OBJECTIVE: We sought to determine the hemodynamic significance of intermediate RAS by measuring translesional systolic pressure gradients (TSPG), using a pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced hyperemia, following selective renal artery angiography. BACKGROUND: Renal artery stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting effectively relieves RAS, however improvement in blood pressure control or renal function is variable and unpredictable. Hemodynamic significance is usually present with RAS when diameter stenosis is >75%, but is less predictable in intermediate (30%-75%) RAS. METHODS: Twenty-two patients (26 renal arteries) with uncontrolled hypertension underwent invasive hemodynamic assessment because of intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS) between 30% and 75% (quantitative DS was measured prospectively). Translesional pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia was induced by administration of intrarenal ACh. RESULTS: Visual and measured angiographic lesion severity did not correlate with TSPG either at baseline (visual DS, R(2) = 0.091, P = 0.13; measured DS, R(2) = 0.124, P = 0.07) or with hyperemia (visual DS, R(2) = 0.057, P = 0.24; measured DS, R(2) = 0.101, P = 0.12). Baseline and maximal hyperemic gradient did correlate (R(2) = 0.567; P < 0.05). Pharmacological provocation produced a significant increase in TSPG (mean; baseline, 18 +/- 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13 patients); 13 (60%) patients subsequently underwent renal artery stenting for hemodynamically significant RAS. At follow-up (at least 30 days), there was a significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19 mm Hg; P < 0.001). CONCLUSIONS: Intrarenal administration of ACh induces hyperemia and can be used to unmask resistive renal artery lesions. Gradient measurement and induced hyperemia may be warranted in the invasive assessment of intermediate renal artery stenoses, rather than relying on stenosis severity alone. Further study is needed to determine whether translesional pressure gradients and pharmacological provocation predict clinical benefit after renal artery stenting.

Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease.

UNLABELLED: Although physical exercise is the preferred stimulus for cardiac stress testing, pharmacologic agents are useful in patients who are unable to exercise. Previous studies have demonstrated short-term repeatability of exercise and adenosine stress, but little data exist regarding dobutamine (Dob) stress or the long-term reproducibility of pharmacologic stressors in coronary artery disease (CAD) patients. PET allows accurate, noninvasive quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The aim of the study was to investigate the long-term reproducibility of Dob stress on MBF and CFR in CAD patients using PET. METHODS: Fifteen patients with chronic stable angina and angiographically proven CAD (>70% stenosis in at least 1 major coronary artery) underwent PET with (15)O-labeled water and Dob stress at baseline (time [t] = 0) and after 24 wk (t = 24). MBF at rest and MBF during Dob stress were calculated for the whole left ventricle, the region subtended by the most severe coronary artery stenosis (Isc), and remote myocardium subtended by arteries with minimal or no disease (Rem). Reproducibility was assessed using the Bland-Altman (BA) repeatability coefficient and was also expressed as a percentage of the mean value of the 2 measurements (%BA). RESULTS: Dob dose (30 +/- 11 vs. 031 +/- 11 microg/kg/min; P = not significant [ns]) and peak Dob rate.pressure product (20,738 +/- 3,947 vs. 20,047 +/- 3,455 mm Hg x beats/min; P = ns) were comparable at t = 0 and t = 24. There was no significant difference in resting or Dob MBF (mL/min/g) between t = 0 and t = 24 for the whole left ventricle (1.03 +/- 0.19 vs. 1.10 +/- 0.20 and 2.02 +/- 0.44 vs. 2.09 +/- 0.57; P = ns for both), Isc (1.05 +/- 0.24 vs. 1.10 +/- 0.26 and 1.79 +/- 0.53 vs. 1.84 +/- 0.62; P = ns for both), or Rem (1.03 +/- 0.23 vs. 1.10 +/- 0.26 and 2.27 +/- 0.63 vs. 2.26 +/- 0.63; P = ns for both) territories. Global (1.98 +/- 0.40 vs. 1.90 +/- 0.46; P = ns) and regional CFR (Isc: 1.65 +/- 0.40 vs. 1.67 +/- 0.47, and Rem: 2.25 +/- 0.57 vs. 2.06 +/- 0.51; P = ns) were reproducible. The BA repeatability coefficients (and %BA) for MBF in ischemic and remote territories were 0.3 (28%) and 0.26 (24%) at rest and 0.49 (27%) and 0.58 (26%) during Dob stress. CONCLUSION: In patients with clinically stable CAD, Dob induces reproducible changes in both global and regional MBF and CFR over a time interval of 24 wk. The reproducibility of MBF and CFR with Dob was comparable with the short-term repeatability reported for adenosine and physical exercise in healthy subjects.

Assessment of ocular and nasal irritation in asthmatics resulting from fragrance exposure.

BACKGROUND: Many asthmatics report worsening of symptoms following exposure to odours and sensory irritants commonly found in household and cosmetic products. Despite this, little evidence exists to confirm the degree to which such subjective reports are correlated with localized, objective changes in the upper or lower airways following a fragranced product exposure. OBJECTIVE: Subjective symptom reports were compared to objective measures in mild asthmatics, moderate asthmatics and non-asthmatics following exposure to one of two fragranced household aerosol mixtures and a clean air control condition to determine if asthmatics reported greater subjective symptoms of nasal congestion or exhibited objective measures of elevated ocular irritation and nasal congestion following exposure than did healthy controls. METHODS: Measures of nasal mucosal swelling, using acoustic rhinometry, and photographic assessments of ocular hyperemia, using macro-photography, were taken before exposure, immediately after an initial 5-min exposure and again following a 30-min exposure to either of two, fragranced aerosol products and a clean air control. Self-reports of nasal patency at each time-point were also obtained. RESULTS: Although moderate asthmatics tended to report more nasal congestion following fragranced product exposure than did non-asthmatics, no exposure-related changes in ocular redness or nasal mucosal swelling were observed among the three groups. Spirometry readings also failed to show evidence of any exposure-related changes in pulmonary function. CONCLUSION: Despite claims that exposure to fragranced products may trigger ocular and respiratory symptoms among asthmatics, we found no evidence that 30 min of exposure to one of two fragranced aerosols elicited objective adverse effects in the ocular or nasal mucosa of mild and moderate asthmatics. While physiological mechanisms of fragrance impact may yet be responsible for some of the adverse reports among asthmatics following fragrance exposure, such reports may also reflect a non-physiological locus of symptom perception triggered by other sensory cues.

Role of incremental doses of intracoronary adenosine for fractional flow reserve assessment.

BACKGROUND: The achievement of maximal vasodilatation of the coronary microvessels is mandatory for the accurate determination of fractional flow reserve (FFR); the optimal dosing to achieve maximal vasodilation is unclear. This study was designed to address the hypothesis that incremental doses of intracoronary adenosine are necessary to ensure complete vasodilatation of the coronary microcirculation and accurate assessment of FFR. We also examined the relationship between FFR and coronary artery disease risk factors. METHODS: A total of 191 patients (215 vessels) with intermediate coronary lesions were examined. FFR was measured during cardiac catheterization with a pressure monitoring wire. Incremental doses of intracoronary adenosine (12-42 microg, left coronary artery; 12-48 microg, right coronary artery) were administered. RESULTS: Diabetes mellitus was present in 23% of patients, hypertension was present in 65% of patients, and prior myocardial infarction had occurred in 25% of patients. The average percent stenosis in vessels was 57% +/- 15%. Vessels were subdivided on the basis of initial FFR (group 1, <0.75; group II, 0.75-0.79; group III, 0.80-0.89; group IV, >or=0.9). Five of the 24 (21%) vessels with an initial FFR in the 0.75 to 0.80 range had a subsequent FFR of <0.75. There was no difference in FFR or doses of adenosine in the patients with coronary artery disease risk factors. The average adenosine dose given at the achievement of minimal FFR was 26 microg in the right coronary artery (RCA) and 34 microg in the left coronary artery (LCA). The average maximum dose of intracoronary adenosine administered was 29 microg for the RCA and 37 microg for the LCA. The maximum dose of adenosine ever required to achieve minimum FFR was 42 microg in both the LCA and RCA. CONCLUSION: This study suggests that a single high dose of 42 microg of intracoronary adenosine for both the RCA and LCA is sufficient to achieve maximum hyperemia and accurate FFR in most patients, independent of risk factors. Alternatively, when a lower initial dose is administered and FFR is in the 0.75 to 0.90 range, incremental doses of adenosine should be administered to ensure maximal hyperemia.

Noninvasive assessment of significant right coronary artery stenosis based on coronary flow velocity reserve in the right coronary artery by transthoracic Doppler echocardiography.

BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE) has been reported to be useful for the noninvasive assessment of coronary stenosis in the left anterior descending artery. However, the measurement of CFVR in the right coronary artery by TTDE has not yet been validated in a clinical study. OBJECTIVE: The aim of this study was to evaluate whether CFVR by TTDE can detect significant stenosis in the right coronary artery. METHODS: We studied 50 patients who underwent coronary angiography. Coronary flow velocity in the posterior descending branch of the right coronary artery (PD) was measured by TTDE both at baseline and during hyperemia induced by the intravenous infusion of adenosine triphosphate. CFVR was calculated as the hyperemia/baseline (average diastolic peak velocity). RESULTS: Adequate spectral Doppler recordings in the PD were obtained in 36 patients including 26 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals. The study population was divided into 2 groups with (Group A;n = 11) and without (Group B;n = 25) significant stenosis in the right coronary artery. CFVR in Group A was significantly smaller than that in Group B (1.6+/-0.3versus2.5+/-0.4; P < 0.0001). The sensitivity of a CFVR of <2.0 for predicting the presence of significant stenosis in the right coronary artery was 91%, and the specificity was 88%. CONCLUSIONS: The measurement of CFVR in the PD by TTDE is useful for the noninvasive assessment of significant stenosis in the right coronary artery.

Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration.

BACKGROUND: Estrogen improves endothelial function in the coronary conduit vessels of animals; however, its effects on the coronary microcirculation have not been studied completely in humans. METHODS AND RESULTS: We measured myocardial blood flow (MBF) with a PET scan at rest, during cold pressor testing (CPT), and during dipyridamole hyperemia in 54 postmenopausal women without coronary artery disease. Of these, 23 were not and 31 women were taking long-term hormone replacement therapy (HRT) using estrogen either alone or with a progestogen. Each group was subdivided by coronary risk factors (RFs). Twelve young healthy women served as controls. In women not taking HRT, MBF measurements were repeated after 25 mg of conjugated equine estrogens IV. Neither short estrogen nor long-term HRT affected MBF at rest in women with and without RFs. Dipyridamole MBF was attenuated only in the women with RF who were not taking HRT. Short-term estrogen and long-term HRT did not reverse the abnormal response. MBF responses to CPT were abnormal in women not taking HRT, regardless of RFs (20+/-15% versus 32+/-21%) and remained unchanged after short-term estrogen administration. Long-term HRT normalized the response to CPT only in women without RF (53+/-22% versus 59+/-36% in the young women; NS). MBFs were similar for women on estrogen alone or estrogen plus a progestogen, regardless of presence or absence of RFs. CONCLUSION: Menopause is associated with abnormal CPT (an indirect measure of endothelial function), which can be reversed by long-term HRT only when RFs are absent. Progestogens do not antagonize this effect. Long-term HRT may therefore be useful in the primary prevention of coronary artery disease in women without RFs.