The effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test

AbstractOBJECTIVESThe aim of this study is to demonstrate the effect of resting ST segment depression on the diagnostic characteristics of the exercise treadmill test.BACKGROUNDPrevious studies evaluating the effect of resting ST segment depression on the diagnostic characteristics of exercise treadmill test have been conducted on relatively small patient groups and based only on visual electrocardiogram (ECG) analysis.METHODSA retrospective analysis of data collected prospectively was performed on consecutive patients referred for evaluation of chest pain. One thousand two hundred eighty-two patients without a prior myocardial infarction underwent standard exercise treadmill tests followed by coronary angiography, with coronary artery disease defined as a 50% narrowing in at least one major epicardial coronary artery. Sensitivity, specificity, predictive accuracy and area under the curve of the receiver operating characteristic (ROC) plots were calculated for patients with and without resting ST segment depression as determined by visual or computerized analysis of the baseline ECG.RESULTSSensitivity of the exercise treadmill test increased in 206 patients with resting ST segment depression determined by visual ECG analysis compared with patients without resting ST segment depression (77 ± 7% vs. 45 ± 4%) and specificity decreased (48 ± 12% vs. 84 ± 3%). With computerized analysis, sensitivity of the treadmill test increased in 349 patients with resting ST segment depression compared with patients without resting ST segment depression (71 ± 6% vs. 42 ± 4%) and specificity decreased (52 ± 9% vs. 87 ± 3%) (p < 0.0001 for all comparisons). There was no significant difference in the area under the curve of the ROC plots (0.66–0.69) or the predictive accuracy (62–68%) between the four subgroups.CONCLUSIONSThe diagnostic accuracy and high sensitivity of the exercise treadmill test in a large cohort of patients with resting ST segment depression and no prior myocardial infarction support the initial use of the test for diagnosis of coronary artery disease. The classification of resting ST segment depression by method of analysis (visual vs. computerized) did not affect the results

Influence of contrast media dose and osmolality on the diagnostic performance of contrast fractional flow reserve

Background—Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance. Methods and Results—cFFR, instantaneous wave–free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR≤0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (P&lt;0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity. Conclusions—The overall accuracy of cFFR is greater than instantaneous wave–free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR

Physiological predictors of acute coronary syndromes: emerging insights from the plaque to the vulnerable patient

In this review, the authors explore the evolving evidence linking physiological assessment of coronary artery disease with plaque progression and vulnerability. Reducing adverse clinical events remains the ultimate goal for diagnostic tests, and this review highlights evidence supporting the prognostic value of physiological metrics in predicting outcomes. Historical and contemporary studies support synergy among lesion severity, ischemia, plaque vulnerability, and patient prognosis. Ischemia contributes to clinical events through association with plaque burden, but this review addresses the emerging concept that it associates with atherothrombosis via disturbed lesion hemodynamics. Biomechanical pathophysiological forces including endothelial shear stress-the frictional force generated by blood flow on the vessel wall-are increasingly linked with atherogenesis, vulnerable plaque morphology, and platelet and leukocyte activation. The authors conclude by transitioning from the model of the vulnerable plaque to the concept of the "vulnerable patient," looking more broadly at physiological contributors to Virchow's triad underpinning acute coronary syndrome

COMPUTED TOMOGRAPHY BASED PREDICTION OF ANGIOGRAPHIC DEPLOYMENT ANGLES MAY REDUCE PROCEDURE TIME AND CONTRAST MEDIUM VOLUME FOR TRANSCATHETER AORTIC VALVE REPLACEMENT

Planas Calvet, LluísPrimer pla d'edifici unifamiliar, de dos habitatges adossats.De planta baixa, planta pis i golfes, i una torrassa adossada. Són de gran qualitat els esgrafiats del número 8 i les elaborades reixes de ferro forjat del número 10

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution

OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. BACKGROUND: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. METHODS: In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. RESULTS: IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. CONCLUSIONS: Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise

Functional SYNTAX Score for Risk Assessment in Multivessel Coronary Artery Disease

ObjectivesThis study was aimed at investigating whether a fractional flow reserve (FFR)-guided SYNTAX score (SS), termed “functional SYNTAX score” (FSS), would predict clinical outcome better than the classic SS in patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).BackgroundThe SS is a purely anatomic score based on the coronary angiogram and predicts outcome after PCI in patients with multivessel CAD. FFR-guided PCI improves outcomes by adding functional information to the anatomic information obtained from the angiogram.MethodsThe SS was prospectively collected in 497 patients enrolled in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined by only counting ischemia-producing lesions (FFR ≤0.80). The ability of each score to predict major adverse cardiac events (MACE) at 1 year was compared.ResultsThe 497 patients were divided into tertiles of risk based on the SS. After determining the FSS for each patient, 32% moved to a lower-risk group as follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium-, and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were independent predictors of 1-year MACE. FSS demonstrated a better predictive accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p = 0.02; integrated discrimination improvement of 1.94%, p < 0.001).ConclusionsRecalculating SS by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with multivessel CAD undergoing PCI. (Fractional Flow Reserve versus Angiography for Multivessel Evaluation [FAME]; NCT00267774

Continuum of vasodilator stress from rest to contrast medium to adenosine hyperemia for fractional flow reserve assessment

Objectives: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). Background: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. Methods: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. Results: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias &lt;0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p &lt; 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. Conclusions: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement

Diversity of symptom phenotypes in SARS-CoV-2 community infections observed in multiple large datasets

Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which infection leads to disease, with different routes requiring potentially different treatment approaches. For public health and control of transmission, symptoms in community cases were the prompt on which action such as PCR testing and isolation was taken. However, interpreting symptoms presents challenges, for instance in balancing sensitivity and specificity of individual symptoms with the need to maximise case finding, whilst managing demand for limited resources such as testing. For both clinical and transmission control reasons, we require an approach that allows for the possibility of distinct symptom phenotypes, rather than assuming variability along a single dimension. Here we address this problem by bringing together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory smartphone surveillance in the United Kingdom. Through use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases, making comparisons across datasets and by age bands. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design.Comment: 52 pages; 25 figure

Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial

In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up