Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .)info:eu-repo/semantics/publishedVersio

Flow-induced compaction of a deformable porous medium.

Fluid flowing through a deformable porous medium imparts viscous drag on the solid matrix, causing it to deform. This effect is investigated theoretically and experimentally in a one-dimensional configuration. The experiments consist of the downwards flow of water through a saturated pack of small, soft, hydrogel spheres, driven by a pressure head that can be increased or decreased. As the pressure head is increased, the effective permeability of the medium decreases and, in contrast to flow through a rigid medium, the flux of water is found to increase towards a finite upper bound such that it becomes insensitive to changes in the pressure head. Measurements of the internal deformation, extracted by particle tracking, show that the medium compacts differentially, with the porosity being lower at the base than at the upper free surface. A general theoretical model is derived, and the predictions of the model give good agreement with experimental measurements from a series of experiments in which the applied pressure head is sequentially increased. However, contrary to theory, all the experimental results display a distinct and repeatable hysteresis: the flux through the material for a particular applied pressure drop is appreciably lower when the pressure has been decreased to that value compared to when it has been increased to the same value.D.R.H. was supported by a Killam Postdoctoral Fellowship and a Research Fellowship at Gonville and Caius College, Cambridge. During the experimental part of this project, J.S.N. was supported by the division of Engineering Science, University of Toronto. J.A.N. is partly supported by a Royal Society University Research Fellowship.This is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevE.93.02311

Collateral donor artery physiology and the influence of a chronic total occlusion on fractional flow reserve

Background— The presence of a concomitant chronic total coronary occlusion (CTO) and a large collateral contribution might alter the fractional flow reserve (FFR) of an interrogated vessel, rendering the FFR unreliable at predicting ischemia should the CTO vessel be revascularized and potentially affecting the decision on optimal revascularization strategy. We tested the hypothesis that donor vessel FFR would significantly change after percutaneous coronary intervention of a concomitant CTO. Methods and Results— In consecutive patients undergoing percutaneous coronary intervention of a CTO, coronary pressure and flow velocity were measured at baseline and hyperemia in proximal and distal segments of both nontarget vessels, before and after percutaneous coronary intervention. Hemodynamics including FFR, absolute coronary flow, and the coronary flow velocity–pressure gradient relation were calculated. After successful percutaneous coronary intervention in 34 of 46 patients, FFR in the predominant donor vessel increased from 0.782 to 0.810 (difference, 0.028 [0.012 to 0.044]; P=0.001). Mean decrease in baseline donor vessel absolute flow adjusted for rate pressure product: 177.5 to 139.9 mL/min (difference −37.6 [−62.6 to −12.6]; P=0.005), mean decrease in hyperemic flow: 306.5 to 272.9 mL/min (difference, −33.5 [−58.7 to −8.3]; P=0.011). Change in predominant donor vessel FFR correlated with angiographic (%) diameter stenosis severity (r=0.44; P=0.009) and was strongly related to stenosis severity measured by the coronary flow velocity–pressure gradient relation (r=0.69; P&lt;0.001). Conclusions— Recanalization of a CTO results in a modest increase in the FFR of the predominant collateral donor vessel associated with a reduction in coronary flow. A larger increase in FFR is associated with greater coronary stenosis severity

Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. -13.8 ± 7.1 × 10(4) W·m(-2)·s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 ± 32.8 vs. -59.4 ± 34.2 × 10(2) W·m(-2)·s(-1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 ± 29.5 × 10(4) W·m(-2)·s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 ± 12.6 × 10(3) W·m(-2)·s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA

Timing of Favorable Conditions, Competition and Fertility Interact to Govern Recruitment of Invasive Chinese Tallow Tree in Stressful Environments

The rate of new exotic recruitment following removal of adult invaders (reinvasion pressure) influences restoration outcomes and costs but is highly variable and poorly understood. We hypothesize that broad variation in average reinvasion pressure of Triadica sebifera (Chinese tallow tree, a major invader) arises from differences among habitats in spatiotemporal availability of realized recruitment windows. These windows are periods of variable duration long enough to permit establishment given local environmental conditions. We tested this hypothesis via a greenhouse mesocosm experiment that quantified how the duration of favorable moisture conditions prior to flood or drought stress (window duration), competition and nutrient availability influenced Triadica success in high stress environments. Window duration influenced pre-stress seedling abundance and size, growth during stress and final abundance; it interacted with other factors to affect final biomass and germination during stress. Stress type and competition impacted final size and biomass, plus germination, mortality and changes in size during stress. Final abundance also depended on competition and the interaction of window duration, stress type and competition. Fertilization interacted with competition and stress to influence biomass and changes in height, respectively, but did not affect Triadica abundance. Overall, longer window durations promoted Triadica establishment, competition and drought (relative to flood) suppressed establishment, and fertilization had weak effects. Interactions among factors frequently produced different effects in specific contexts. Results support our ‘outgrow the stress’ hypothesis and show that temporal availability of abiotic windows and factors that influence growth rates govern Triadica recruitment in stressful environments. These findings suggest that native seed addition can effectively suppress superior competitors in stressful environments. We also describe environmental scenarios where specific management methods may be more or less effective. Our results enable better niche-based estimates of local reinvasion pressure, which can improve restoration efficacy and efficiency by informing site selection and optimal Management

85 Prediction of response to biventricular pacing from dyssynchrony indices: the absolute limit on predictability, and its clinical implications

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Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

Background: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff

Effects of disease severity distribution on the performance of quantitative diagnostic methods and proposal of a novel ‘V-plot’ methodology to display accuracy values

BACKGROUND: Diagnostic accuracy is widely accepted by researchers and clinicians as an optimal expression of a test’s performance. The aim of this study was to evaluate the effects of disease severity distribution on values of diagnostic accuracy as well as propose a sample-independent methodology to calculate and display accuracy of diagnostic tests. METHODS AND FINDINGS: We evaluated the diagnostic relationship between two hypothetical methods to measure serum cholesterol (Chol_{rapid} and Chol_{gold} by generating samples with statistical software and (1) keeping the numerical relationship between methods unchanged and (2) changing the distribution of cholesterol values. Metrics of categorical agreement were calculated (accuracy, sensitivity and specificity). Finally, a novel methodology to display and calculate accuracy values was presented (the V-plot of accuracies). CONCLUSION: No single value of diagnostic accuracy can be used to describe the relationship between tests, as accuracy is a metric heavily affected by the underlying sample distribution. Our novel proposed methodology, the V-plot of accuracies, can be used as a sample-independent measure of a test performance against a reference gold standard

Diagnostic accuracy of computed tomography-derived fractional flow reserve a systematic review

Importance Computed tomography–derived fractional flow reserve (FFR-CT) is a novel, noninvasive test for myocardial ischemia. Clinicians using FFR-CT must be able to interpret individual FFR-CT results to determine subsequent patient care. Objective To provide clinicians a means of interpreting individual FFR-CT results with respect to the range of invasive FFRs that this interpretation might likely represent. Evidence Review We performed a systematic review in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic search of MEDLINE (January 1, 2011, to 2016, week 2) and EMBASE (January 1, 2011, to 2016, week 2) was performed for studies assessing the diagnostic accuracy of FFR-CT. Title words used were computed tomography or computed tomographic and fractional flow reserve or FFR. Results were limited to publications in peer-reviewed journals. Duplicate studies and abstracts from scientific meetings were removed. All of the retrieved studies, including references, were reviewed. Findings There were 908 vessels from 536 patients in 5 studies included in the analysis. A total of 365 (68.1%) were male, and the mean (SD) age was 63.2 (9.5) years. The overall per-vessel diagnostic accuracy of FFR-CT was 81.9% (95% CI, 79.4%-84.4%). For vessels with FFR-CT values below 0.60, 0.60 to 0.70, 0.70 to 0.80, 0.80 to 0.90, and above 0.90, diagnostic accuracy of FFR-CT was 86.4% (95% CI, 78.0%-94.0%), 74.7% (95% CI, 71.9%-77.5%), 46.1% (95% CI, 42.9%-49.3%), 87.3% (95% CI, 85.1%-89.5%), and 97.9% (95% CI, 97.9%-98.8%), respectively. The 82% (overall) diagnostic accuracy threshold was met for FFR-CT values lower than 0.63 or above 0.83. More stringent 95% and 98% diagnostic accuracy thresholds were met for FFR-CT values lower than 0.53 or above 0.93 and lower than 0.47 or above 0.99, respectively. Conclusions and Relevance The diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. This analysis allows clinicians to interpret the diagnostic accuracy of individual FFR-CT results. In combination with patient-specific factors, clinicians can use FFR-CT to judge when the cost and risk of an invasive angiogram may safely be avoided