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.

[Results of a clinical study of the combination of flurbiprofen and cetylpyridinium chloride in patients with sore throat]. / Rezul'taty klinicheskogo issledovaniya kombinatsii flurbiprofena i tsetilpiridiniya khlorida u patsientov s bol'yu v gorle.

Sore throat is one of the most frequent complaints with which patients seek medical help from an otorhinolaryngologist, therapist and pediatrician. OBJECTIVE: To evaluate the efficacy and safety of a combined topical drug with flurbiprofen and cetylpyridinium chloride in patients with sore throat caused by upper respiratory tract infections. MATERIAL AND METHODS: A prospective multicenter open randomized comparative study in parallel groups included 266 adult patients with an established diagnosis of acute pharyngitis or acute tonsillitis aged 18 to 60 years with the main complaint of sore throat caused by viral infections of the upper respiratory tract. The patients included in the study were randomized into two groups of 133 participants each: the 1st group included patients who received the combined agent flurbiprofen 8.75 mg and cetylpyridinium chloride 1.00 mg in the form of tablets for resorption, the 2nd group included patients who received cetylpyridinium chloride 1.2 mg in the form of medicinal lozenges. The effectiveness was evaluated on several scales (RADT, STPIS, TPA, STPR) reflecting subjective and objective indicators of the dynamics of the disease. RESULTS: The studied combination proved to be more effective than the monocomponent agent and was characterized by a more pronounced decrease in sore throat within 2 hours after taking the drug and a decrease in pharyngeal hyperemia. CONCLUSION: According to the results of the study, the use of a drug based on a combination of flurbiprofen and cetylpyridinium chloride was accompanied by a rapid and pronounced decrease in sore throat and pharyngeal hyperemia in patients with upper respiratory tract infections.

[Results of the clinical study of the combination of flurbiprofen and cetylpyridinium chloride in patients with sore throat]. / Rezul'taty klinicheskogo issledovaniya kombinatsii flurbiprofena i tsetilpiridiniya khlorida u patsientov s bol'yu v gorle.

Sore throat is one of the most frequent complaints with which patients seek medical help from an otorhinolaryngologist, therapist and pediatrician. OBJECTIVE: To evaluate the efficacy and safety of a combined topical drug with flurbiprofen and cetylpyridinium chloride compared with a monocomponent drug in patients with sore throat associated with manifestations of acute pharyngitis, tonsillitis or with exacerbation of chronic forms of pharyngitis or tonsillitis. MATERIAL AND METHODS: A prospective, multicenter, open, randomized, comparative study in parallel groups included 266 adult patients aged 18 to 60 years with an established diagnosis of acute pharyngitis or acute tonsillitis with the main complaint of sore throat caused by viral infections of the upper respiratory tract. The patients included in the study were randomized into two groups of 133 participants each: the 1st group included patients who received the combined agent flurbiprofen 8.75 mg and cetylpyridinium chloride 1.0 mg in the form of tablets for resorption; the 2nd group included patients who received cetylpyridinium chloride 1.2 mg in the form of medicinal lozenges. The effectiveness was evaluated on three scales - STPIS, TPA, STPR, reflecting indicators of the dynamics of the disease. RESULTS: The studied combination turned out to be more effective than the monocomponent remedy and was characterized by a more pronounced decrease in the intensity of sore throat within 2 hours after taking the drug and a decrease in pharyngeal hyperemia. CONCLUSION: According to results of the study, the use of a drug based on the combination of flurbiprofen and cetylpyridinium chloride was accompanied by a rapid and pronounced decrease in the intensity of sore throat and pharyngeal hyperemia in patients with upper respiratory tract infections.

Usefulness of the Hybrid RFR-FFR Approach: Results of a Prospective and Multicenter Analysis of Diagnostic Agreement between RFR and FFR-The RECOPA (REsting Full-Cycle Ratio Comparation versus Fractional Flow Reserve (A Prospective Validation)) Study.

BACKGROUND: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. MATERIALS AND METHODS: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). RESULTS: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. CONCLUSIONS: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.

Retrospective analysis of adverse events with dupilumab reported to the United States Food and Drug Administration.

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated. OBJECTIVE: To classify the most common adverse reactions associated with dupilumab treatment in patients with AD. METHODS: The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group. RESULTS: The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab. LIMITATIONS: Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated. CONCLUSIONS: Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates.

Clinical Efficacy of Intracoronary Papaverine After Nicorandil Administration for Safe and Optimal Fractional Flow Reserve Measurement.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Index of Microcirculatory Resistance Measured during Intracoronary Adenosine-Induced Hyperemia.

BACKGROUND: The index of microcirculatory resistance is an invasive measure of coronary microvascular function that has to be calculated during maximal hyperemia, classically achieved with intravenous adenosine (IV). The aim of this study was to evaluate the use of intracoronary (IC) adenosine for the calculation of IMR. METHODS AND RESULTS: 31 patients with stable coronary artery disease were included in the study. Coronary pressure and thermodilution measurements were obtained at rest and during maximal hyperemia using a pressure-temperature sensor-tipped coronary guidewire. Duplicate measurements were performed using first IC and then IV adenosine. Dispersion of transit times was comparable for IC and IV adenosine. IMR values based on IC vs IV adenosine showed a high level of agreement and an intraclass correlation coefficient of 0.90. Applying an upper normal limit of 25, misclassification of IMR using IC adenosine was seen in just one patient in whom IC adenosine resulted in a lower value. A simplified procedure based on a single bolus dose of saline did not change the level of agreement or the rate of misclassification. CONCLUSIONS: We found an excellent agreement between IMR values measured during hyperemia induced by IC as compared to IV adenosine. The use of IC adenosine may facilitate invasive assessment of microvascular function and is potentially time- and cost-saving with less patient discomfort as compared to IV infusion. The trail is registered with NCT03369184.

Reactive hyperemia and baseline pulse amplitude among smelter workers exposed to fine and ultrafine particles.

OBJECTIVE: Ambient exposure to fine particles is associated with increased cardiovascular morbidity and mortality. Associations between occupational particulate matter (PM) exposure and cardiovascular disease have been studied less. The objective of this study was to examine associations between PM exposure and endothelial function among workers in Norwegian smelters. METHODS: We examined endothelial function with Endo-PAT equipment after a working day (WD) and on a day off (DO) in 59 furnace workers recruited from three metal smelters in Norway. The difference in baseline pulse amplitude (BPA) and reactive hyperemia index (RHI) between the 2 days was analysed in relation to individual exposure to PM < 250 nm (PM250) or the respirable aerosol fraction of particles, and adjusted for relevant covariates. RESULTS: The exposure to PM250 ranged from 0.004 to 5.7 mg/m3. The mean BPA was significantly higher on WD relative to DO (772 vs. 535, p = 0.001). This difference was associated with PM concentrations among participants ≥ 34 years, but not among the younger workers. Reactive hyperemia was significantly lower on workdays relative to days off (1.70 vs. 1.84, p = 0.05). This difference was observed only among participants above the age 34. No associations with PM exposure were observed. CONCLUSIONS: PM exposure was associated with higher BPA among participants older than 34 years. BPA reflects microvessel pulsatility. Our results may indicate an age-dependent cardiovascular susceptibility to PM exposure. Endothelial function measured by RHI was reduced on WD among participants 34 years and older, but we found no associations between PM exposure and RHI.

White Sclera Painted Contact Lens for Masking of Conjunctival Neovascularization and Hyperemia Following Cosmetic Eye Whitening Procedure.

We describe a case of a 37-year-old veteran with recurrent conjunctival hyperemia 5 years after an eye-whitening conjunctivectomy procedure with mitomycin C who desired to have a repeat procedure by the original surgeon. Instead, the patient was counseled and successfully fitted with white sclera painted contact lenses to mask the regrowth of his conjunctival vasculature with excellent cosmetic results and comfort. Further eye-whitening surgery was, therefore, avoided. We conclude that hand-painted white sclera contact lenses with regular ocular surface health monitoring can be offered as a cosmetic, safer, and economical alternative to patients in order to avoid eye-whitening procedures known to induce ocular ischemia.

Arteriolar and capillary responses to CO2 and H+ in hamster skeletal muscle microvasculature: Implications for active hyperemia.

OBJECTIVE: We hypothesized that CO2 and H+ stimulate capillaries and arterioles to produce local and conducted vasodilations required to coordinate the distribution of blood flow to contracting skeletal muscle fibers. METHODS: CO2 and H+ independently and in combination were applied to 2A arterioles (first branch order from the 1A feed arteriole) and capillaries of the in situ, blood-perfused hamster cremaster muscle. The resulting local and conducted vasodilations were measured. RESULTS: H+ (pH: 7.2-6.6) and CO2 (5% and 10%) applied to the vascular network induced 2A arteriolar vasodilations, while 15% CO2 produced vasoconstriction. Localized application of H+ produced 2A arteriolar vasodilation, while 15% CO2 resulted in a variable response. Simultaneous application of CO2 and H+ did not result in the predicted additive effects. Application of CO2 and H+ alone or combined on arterioles or capillaries did not induce a conducted response. CONCLUSIONS: CO2 and H+ produce arteriolar vasodilation but, critically, cannot stimulate the spread of vasodilation throughout the network, thus limiting their ability to coordinating blood flow to contracting skeletal muscle fibers. Given their potential for interaction, the importance of CO2 and H+ may lie in their ability to modify the effects of other vasodilators.

Temporal dissociation between the minimal distal-to-aortic pressure ratio and peak hyperemia during intravenous adenosine infusion.

The present study sought to compare the temporal relation between maximal coronary flow (peak hyperemia) and minimal coronary-to-aortic pressure ratio (Pd/Pa) for intracoronary (IC) and intravenous (IV) adenosine administration. Peak hyperemia is assumed to coincide with the minimal Pd/Pa value. However, this has not been confirmed for systemic hemodynamic variations during IV adenosine infusion. Hemodynamic responses to IV and IC adenosine administration were obtained in 12 patients (14 lesions) using combined IC pressure and flow velocity measurements. A fluid dynamic model was used to predict the change in Pd/Pa for different stenosis severities and varying Pa Hemodynamic variability during IV adenosine hyperemia was greater than during IC adenosine, as assessed by the coefficient of variation. During IV adenosine, flow velocity peaked 28 ± 4 (SE) s after the onset of hyperemia, while Pd/Pa reached a minimum (0.82 ± 0.01) 22 ± 7 s later (P < 0.05), when Pa had declined by 6.1% and hyperemic velocity by 4.5% (P < 0.01). Model outcomes corroborated the role of variable Pa in this dissociation. In contrast, maximal flow and minimal Pd/Pa coincided for IC adenosine, with IV-equivalent peak velocities and a higher Pd/Pa ratio (0.86 ± 0.01, P < 0.01). Hemodynamic variability during continuous IV adenosine infusion can lead to temporal dissociation of minimal Pd/Pa and peak hyperemia, in contrast to IC adenosine injection, where maximal velocity and minimal Pd/Pa coincide. Despite this variability, stenosis hemodynamics remained stable with both ways of adenosine administration. Our findings suggest advantages of IC over IV adenosine to identify maximal hyperemia from pressure-only measurements.NEW & NOTEWORTHY Systemic hemodynamic variability during intravenous adenosine infusion produces substantial temporal dissociation between peak hyperemia appraised by coronary flow velocity and the minimal distal-to-aortic pressure ratio commonly used to determine functional stenosis severity. This dissociation was absent for intracoronary adenosine administration and tended to be mitigated in patients receiving Ca2+ antagonists.

The Ocular Hypotensive Efficacy of Topical Fasudil, a Rho-Associated Protein Kinase Inhibitor, in Patients With End-Stage Glaucoma.

To investigate the effects of topical administration of a selective Rho-associated kinase (ROCK) inhibitor, fasudil 0.5% and 1.2% in glaucomatous patients. In this interventional case series study, 4 eyes of 4 patients with unilateral end-stage primary open-angle glaucoma and no light perception vision were assigned to receive topical fasudil 0.5% (in 3 eyes) or 1.2% (in 1 eye) ophthalmic solution twice daily for 8 weeks. At weeks 1, 2, 3, 4, and 8, intraocular pressure (IOP) and adverse events were evaluated. Baseline mean IOP was 53.5 ± 3.4 mm Hg and mean IOP reductions of the last visit were -8.25 ± 1.2 mm Hg at 2 hours and -8.75 ± 2.2 mm Hg at 4 hours. Mean IOP reductions were clinically and statistically significant with 0.5% and 1.2% fasudil and peak effects occurred 2-4 hours after application (P = 0.0002). The largest IOP reductions were produced by 1.2% fasudil (up to -12 mm Hg). Conjunctival hyperemia was found in 1 patient with 1.2% fasudil. Topical administration of fasudil in end-stage primary open-angle glaucoma patients, caused reduction in IOP and was well tolerated. ROCK inhibitors could be considered as a candidate for glaucoma therapy in future.

Physicochemical/photophysical characterization and angiogenic properties of Curcuma longa essential oil.

This study analyzed the physicochemical and photophysical properties of essential oil of Curcuma longa and its angiogenic potential. The results showed that curcumin is the main fluorescent component present in the oil, although the amount is relatively small. The experimental chorioallantoic membrane model was used to evaluate angiogenic activity, showing a significant increase in the vascular network of Curcuma longa and positive control groups when compared to the neutral and inhibitor controls (P <0.05), but no significant difference was found between Curcuma longa essential oil and the positive control (P >0.05). Histological analysis showed extensive neovascularization, hyperemia and inflammation in the positive control group and Curcuma longa when compared to other controls (P <0.05), characteristic factors of the angiogenesis process. In conclusion, Curcuma longa oil showed considerable proangiogenic activity and could be a potential compound in medical applications.

Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults.

In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF.

[Impact of blood pressure control on coronary flow reserve in hypertensive patients].

OBJECTIVE: To investigate the impacts of blood pressure control on coronary flow reserve (CFR) in hypertensive patients. METHODS: A total of 236 patients without significant coronary stenosis (defined as <50% luminal narrowing which was confirmed by coronary angiography or coronary artery CT scan) between January 2011 to July 2015 were retrospectively enrolled in this study. CFR was measured in the left anterior descending coronary artery (LAD) during adenosine triphosphate-induced hyperemia by transthoracic Doppler echocardiography. Patients were divided into hypertension group (n=173) and non-hypertension group (n=63). The hypertension patients were further divided into ideally controlled (n=31, defined as SBP <120 mmHg (1 mmHg=0.133 kPa) and DBP <80 mmHg), controlled (n=82, defined as SBP 120 to 139 mmHg and DBP <90 mmHg) and uncontrolled groups (n=60, defined as SBP≥140 mmHg and/or diastolic DBP≥90 mmHg) based on their blood pressure after systematic antihypertensive therapy and CFR values were compared among the 4 groups. Multivariate regression analyses were performed to identify the independent determinants of CFR in patients with hypertension. RESULTS: Compared with non-hypertension group, the CFR was significantly lower in controlled (3.27±0.71 vs. 2.87±0.56, P<0.001) and uncontrolled groups (3.27±0.71 vs. 2.61±0.71, P<0.001), but was similar in ideally controlled group (3.27±0.71 vs. 3.21±0.85, P=0.68). Furthermore, the CFR was significantly lower in uncontrolled group than that of the other two hypertension groups and was significantly lower in controlled group than that of ideally controlled group. Higher blood pressure (ß=-0.17, P=0.03) and age(ß=-0.02, P=0.03) were independent predictors of lower CFR in patients with hypertension. CONCLUSIONS: Higher blood pressure is an independent predictor of decreased CFR in patients with hypertension. Hypertensive patients with ideally controlled blood pressure have similar CFR level as patients without hypertension.

Impact of antipsoriatic therapy on endothelial function.

BACKGROUND: Endothelial function (EF) impairment is one of the first events in the process of atherosclerosis, which is known to be associated with psoriasis. Nevertheless, the effect of antipsoriatic treatments, some of them with atherogenic risks, on cardiovascular morbidity and EF is still unclear. OBJECTIVES: To investigate the effect of short-term antipsoriatic treatments on EF values as a potential marker of their effect on cardiovascular morbidity. METHODS: EF was evaluated in 26 patients with moderate-to-severe psoriasis by measuring microvascular blood flow, expressed as the reactive hyperaemia index (RHI), before and after phototherapy (8 weeks) or systemic antipsoriatic treatment (12 weeks). RESULTS: Antipsoriatic intervention was effective (46% achieving ≥ 75% improvement in Psoriasis Area and Severity Index), while the average RHI did not improve during the study (1·73 ± 0·48. vs. 1·66 ± 0·35, average difference -0·12 ± 0·43, not significant). Patients with baseline preserved EF exhibited a decline in RHI (difference -0·2 ± 0·4, P = 0·053), while patients with abnormal baseline RHI presented nonsignificant RHI improvement (RHI difference 0·1 ± 0·2). CONCLUSIONS: There was no positive effect on EF of short-term antipsoriatic treatment. It is possible that a longer period of treatment and EF evaluation would uncover a positive endothelial effect, especially in patients with baseline abnormal EF.

Variability of fractional flow reserve according to the methods of hyperemia induction.

OBJECTIVES: We performed this study to evaluate the variability of fractional flow reserve (FFR) values which were measured from various methods of hyperemia induction. BACKGROUND: Concerns have been raised regarding the variability of FFR due to different routes for hyperemic agent administration and different hyperemic agents targeting different receptors to induce maximal hyperemia. METHODS: A total of 656 intermediate coronary lesions from 628 patients with coronary artery disease were analyzed. Among them, 238 lesions underwent FFR measurement with hyperemia induced by both intravenous (IV) and intracoronary (IC) adenosine administration, 318 by IV adenosine/adenosine triphosphate (ATP) and IC nicorandil injection, and 100 by IV adenosine and regadenoson infusion. RESULTS: Excellent correlation and close classification agreement (FFR ≤ 0.80) were observed between IV vs. IC adenosine (r = 0.980, CA = 92.9%, Cohen's Kappa = 0.887, P < 0.001), between IV adenosine/ATP vs. IC nicorandil (r = 0.962, CA = 91.2%, Cohen's Kappa = 0.817, P < 0.001), and between IV adenosine vs. regadenoson (r = 0.990, CA = 100%, Cohen's Kappa = 1.000, P < 0.001). When changes in blood pressure (ΔBP) or heart rate (ΔHR) were compared with changes in FFR (ΔFFR) between IV adenosine/ATP and IC nicorandil administration, there were no significant correlations between ΔBP and ΔFFR nor between ΔHR and ΔFFR (r = -0.122, P = 0.076; r = 0.036, P = 0.605, respectively). CONCLUSIONS: This study suggests that the measurement of FFR is reproducible regardless of the hemodynamic changes, hyperemic agents used, or the route of administration.

Long-term outcome after deferral of revascularization in patients with intermediate coronary stenosis and gray-zone fractional flow reserve.

BACKGROUND: A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS: We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS: Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Advances in coronary physiology.

Pressure-wire technology, most typically fractional flow reserve (FFR), has provided interventional cardiologists with a means of determining the physiological importance of a stenosis during angiography. There has been renewed interest in coronary physiology in the light of guideline recognition, ongoing clinical research and new technologies changing the paradigm of how assessment is performed in the catheter laboratory. We reflect on FFR, with regards the potential effects of changing hemodynamics on FFR and the latest evidence with regards to outcomes. We also review the instantaneous wave-free ratio (iFR), a new pressure-only index, measured at rest, that is under active evaluation in several international randomized controlled trials. We review the accumulated evidence and discuss the important physiological concepts between pressure and flow that underlie the approach to using resting indices. Finally we investigate future developments, including physiological mapping with iFR-Pullback and the potential to predict the hemodynamic effect of stenting.

Effect of benzalkonium chloride-free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study.

BACKGROUND: Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). METHODS: This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan® preserved with POLYQUAD® [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of ≤18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study. RESULTS: All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P < 0.001 for both). A greater percentage of patients achieved a target IOP of ≤18 mmHg at week 6 (93.1 %; n = 163/175) and week 12 (93.3 %; n = 166/178) compared with baseline (89.5 %; n = 171/191). There was a 10.5 % increase in the percentage of patients with "none/trace" amounts of hyperemia. Most patients preferred the study medication (81.5 %; n = 141/173) and were confident that they would adhere to their preferred medication (90.8 %; n = 157/173). No serious AEs were reported, and eye irritation (3.7 %; n = 7/191) was the most common treatment-related AE. CONCLUSIONS: Transitioning from BAK-containing latanoprost 0.005 % to BAK-free travoprost 0.004 % preserved with PQ reduced IOP in patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01510145.