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Objectives: The aim of this study was to assess clinical outcomes after combined pressure and flow assessment of coronary lesions. Background: Although fractional flow reserve (FFR) remains the invasive reference standard for revascularization, approximately 40% of stenoses have discordant coronary flow reserve (CFR). Optimal treatment for these disagreements remains unclear. Methods: A total of 455 subjects with 668 lesions were enrolled from 12 sites in 6 countries. Only lesions with reduced FFR and CFR underwent revascularization; all other combinations received initial medical therapy. Results: Fourteen percent of lesions had FFR ≤0.8 but CFR ≥2.0 while 23% of lesions had FFR >0.8 but CFR 0.8 and CFR ≥2.0 (6.2% event rate) exceeded the prespecified +10% noninferiority margin (P = 0.090). Target vessel failure models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P = 0.007) after initial medical treatment. Central core laboratory review accepted 69.8% of all tracings with mean differences of 0.8 and CFR ≥2.0. These results do not support using invasive CFR ≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference.

Although our coronary circulation evolved to meet demands during marked physical exertion for “fight or flight” survival, complex and multilayered control mechanisms reduce flow during oth...

This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization.The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown.Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization.Severely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone.CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.

Background: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases. Optimal management of these discordant cases requires further study. Aim: The aim of the study was to determine the prognostic value of combined FFR and CFR measurements to predict the 24-month rate of major adverse cardiac events. Secondary end points include repeatability of FFR and CFR, angina burden, and the percentage of successful FFR/CFR measurements which will not be excluded by the core laboratory. Methods: This prospective, nonblinded, nonrandomized, and multicenter study enrolled 455 subjects from 12 sites in Europe and Japan. Patients underwent physiologic lesion assessment using the 0.014” Philips Volcano ComboWire XT that provides simultaneous pressure and Doppler velocity sensors. Intermediate coronary lesions received only medical treatment unless both FFR (≤0.8) and CFR ( 0.80 and CFR ≥ 2.0. Enrollment has been completed, and final follow-up will occur in November 2019.

Background PET quantitative myocardial perfusion requires correction for partial volume loss due to one-dimensional LV wall thickness smaller than scanner resolution. Methods We aimed to assess accuracy of risk stratification for death, MI, or revascularization after PET using partial volume corrections derived from two-dimensional ACR and three-dimensional NEMA phantoms for 3987 diagnostic rest–stress perfusion PETs and 187 MACE events. NEMA, ACR, and Tree phantoms were imaged with Rb-82 or F-18 for size-dependent partial volume loss. Perfusion and Coronary Flow Capacity were recalculated using different ACR- and NEMA-derived partial volume corrections compared by Kolmogorov–Smirnov statistics to standard perfusion metrics with established correlations with MACE. Results Partial volume corrections based on two-dimensional ACR rods (two equal radii) and three-dimensional NEMA spheres (three equal radii) over estimate partial volume corrections, quantitative perfusion, and Coronary Flow Capacity by 50% to 150% over perfusion metrics with one-dimensional partial volume correction, thereby substantially impairing correct risk stratification. Conclusions ACR (2-dimensional) and NEMA (3-dimensional) phantoms overestimate partial volume corrections for 1-dimensional LV wall thickness and myocardial perfusion that are corrected with a simple equation that correlates with MACE for optimal risk stratification applicable to most PET-CT scanners for quantifying myocardial perfusion.

Objectives We sought to develop an automatic method for correcting common errors in phasic pressure tracings for physiology‐guided interventions on coronary and valvular stenosis. Background Effective coronary and valvular interventions rely on accurate hemodynamic assessment. Phasic (subcycle) indexes remain intrinsic to valvular stenosis and are emerging for coronary stenosis. Errors, corrections, and clinical implications of fluid‐filled catheter phasic pressure assessments have not been assessed in the current era of ubiquitous, high‐fidelity pressure wire sensors. Methods We recruited patients undergoing invasive coronary physiology assessment. Phasic aortic pressure signals were recorded simultaneously using a fluid‐filled guide catheter and 0.014″ pressure wire before and after standard calibration as well as after pullback. We included additional subjects undergoing hemodynamic assessment before and after transcatheter aortic valve implantation. Using the pressure wire as reference standard, we developed an automatic algorithm to match phasic pressures. Results Removing pressure offset and temporal shift produced the largest improvements in root mean square (RMS) error between catheter and pressure wire signals. However, further optimization

ObjectiveThis study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease.MethodsThis is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA).ResultsMean FFR and CFR were 0.82±0.10 and 2.2±0.6, respectively. When divided according to FFR and CFR thresholds (above and below 0.80 and 2.0, respectively), HMR was highest in lesions with FFR>0.80 and CFR2=0.98, pConclusionsIncreased HMR was not associated with a higher rate of adverse clinical events, in this population of mainly stable patients. FFR can be equally well expressed as HMR/HMR+HSR, thereby providing an alternative conceptual formulation linking epicardial severity with microvascular resistance.Trial registration numberNCT02328820.

Subendocardial ischemia is commonly diagnosed but not quantified by imaging.This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ)1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90).Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.

To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE).Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs).Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.

Purpose of ReviewThe COURAGE and ISCHEMIA trials showed no reduced mortality after revascularization compared to medical treatment. Is this lack of benefit due to revascularization having no benefit regardless of CAD severity or to suboptimal patient selection due to non-quantitative cardiac imaging?Recent FindingsComprehensive, integrated, myocardial perfusion quantified by regional pixel distribution of coronary flow capacity (CFC) is the final common expression of objective CAD severity for which revascularization reduces mortality. Current lack of revascularization benefit derives from narrow thinking focused on measuring one isolated aspect of coronary characteristics, such as angiogram stenosis, its fractional flow reserve (FFR), anatomic FFR simulations, relative stress imaging, absolute stress ml/min/g or coronary flow reserve (CFR) alone, or even more narrowly on global CFR or fixed regions of interest in assumed coronary artery distributions, or in arbitrary 17 segments on bull’s-eye displays, rather than regional pixel distribution of perfusion metrics as they actually are in an individual.SummaryComprehensive integration of all quantitative perfusion metrics per regional pixel into coronary flow capacity guides artery-specific interventions for reduced mortality in non-acute CAD but requires addressing the methodologic questions in the title.

Quantitative myocardial perfusion by positron emission tomography (PET) is the optimal guide for diagnosis and management or interventions for obstructive or non-obstructive coronary artery disease (CAD) for the following reasons documented in this chapter: PET guided elective revascularization in chronic CAD reduces death and myocardial infarction (MI) by 54% compared to medical treatment alone whereas FFR or FFRct or angiogram guided interventions show no reduced death or MI compared to medical treatment. In a large cohort with high prevalence of CAD, PET excludes 60–80% of elective coronary angiograms as unnecessary for mild or moderate, low risk CAD not needing angiogram versus identifying patients with CAD severity getting PCI or CABG in 78% of PET guided angiograms. By comparison, for FFRct ≤0.8, only 38% have pressure derived FFR ≤0.8 at angiogram, hence FFRct is false + in 62% of + FFRct cases. On head to head comparison with analysis for intent to diagnose, PET is superior to FFRct on a per patient and per artery analysis due FFRct variability of ±25% for predicting FFR ≤0.8 and due to 17% FFRct failures of acquiring useable data versus 0.7% failed data acquisition for PET that has ±10% variability. In addition to this data, PET quantitative perfusion is the accepted Gold Standard of physiologic CAD severity since: (i) PET is the reference standard to which FFR was compared for validation and for the extensive PET literature since validating FFR. (ii) Quantitative myocardial perfusion explains symptoms and abnormal physiologic function broadly in all coronary pathophysiologies to guide management. (iii) Quantitative myocardial perfusion by PET has mainstream status in cardiology texts including Hurst’s The Heart and The Atlas of Nuclear Cardiology (in press).

Kolmogorov–Smirnov (KS) statistic is a non-parametric statistic based on the empirical distribution function. For the one-sample case, it uses the supremum distance between an empirical distribution function (EDF) and a pre-specified cumulative distribution function (CDF). For two-sample case, it measures the maximum of the distance between two EDFs. KS test, as well as other EDF-based tests such as the Anderson-Darling (AD) test and Cramer-von Mises (CvM) test, has been widely used in statistical analysis. To address and compare the performance of these test statistics, we have conducted a simulation study comparing the type I error and power of the KS test, the CvM test, the AD test, and the Chi-squared test. Our study includes both one sample and two sample tests and for both independent and correlated samples. Our study showed that if we do not have prior information about the tested distributions, EDF-based tests are better. However, so long as we have prior information about the tested distribution and the density of two distributions is bell-shaped and we are expecting differences in variance/sparseness, then the Chi-squared test may be more preferable. When correlation exists between tested samples, adjustment on the informative sample size is important and required.

Although our coronary circulation evolved to meet demands during marked physical exertion for "fight or flight" survival, complex and multilayered control mechanisms reduce flow during other periods. Understanding homeostasis of resting flow provides essential insights into clinical pathophysiology. Several homeostatic mechanisms (myogenic, metabolic, endothelial, and neural) maintain sufficient baseline flow regardless of driving pressure (in aggregate, "autoregulation"). As a result, ventricular dysfunction does not arise until coronary perfusion pressure decreases to ∼40 mm Hg. Straightforward clinical parameters explain approximately one-half of observed absolute resting perfusion but with wide imprecision. Resting perfusion does not associate with clinical outcomes and remains unaffected by revascularization, recovery after myocardial infarction, and treating severe aortic stenosis, thereby supporting the notion that the heart was designed for peak performance.

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave‐free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect ‐Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian‐Dutch‐English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively; P 50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR ( P P Conclusions CFC showed significant improvement of identification of lesions that benefit from revascularization compared with CFR with respect to coronary flow increase. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02328820.

With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and define severity. A better understanding of the microvasculature in AS could improve clinical care by predicting left ventricular remodeling or anticipate the interplay between epicardial stenosis and myocardial dysfunction. In this review, we combine five decades of literature regarding microvascular, coronary, and aortic valve physiology with emerging insights from newly developed invasive tools for quantifying microcirculatory function. Furthermore, we describe the coupling between microcirculation and epicardial stenosis, which is currently under investigation in several randomized trials enrolling subjects with concomitant AS and coronary disease. To clarify the physiology explained previously, we present two instructive cases with invasive pressure measurements quantifying coexisting valve and coronary stenoses. Finally, we pose open clinical and research questions whose answers would further expand our knowledge of microvascular dysfunction in AS. These trials were registered with NCT03042104, NCT03094143, and NCT02436655.

Purpose of Review This review discusses similarities and differences between cardiac positron emission tomography (PET), absolute myocardial blood flow, and flow reserve with invasive fractional flow reserve (FFR). Recent Findings Fundamentally, cardiac PET measures absolute myocardial blood flow whereas FFR provides a relative flow reserve. Cardiac PET offers a non-invasive and therefore lower risk alternative, able to image the entire left ventricle regardless of coronary anatomy. While cardiac PET can provide unique information about the subendocardium, FFR pullbacks offer unparalleled spatial resolution. Both diagnostic tests provide a highly repeatable and technically successful index of coronary hemodynamics that accounts for the amount of distal myocardial mass, albeit only indirectly with FFR. The randomized evidence base for FFR and its associated cost effectiveness remains unsurpassed. Summary Cardiac PET and FFR have been intertwined since the very development of FFR over 25 years ago. Recent work has emphasized the ability of both techniques to guide revascularization decisions by high-quality physiology. In the past few years, cardiac PET has expanded its evidence base regarding clinical outcomes, whereas FFR has solidified its position in randomized studies as the invasive reference standard.

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

Angina with no angiographic stenosis, commonly called “microvascular angina,” encompasses a wide continuum of coronary pathophysiology in conflicting published reports. Comprehensive quantitative myocardial perfusion offers new insights beyond overly simplistic coronary flow reserve. Integrating regional absolute stress flow, relative stress flow, coronary flow reserve, and qualitative subendocardial perfusion gradient on tomograms of relative images, provides correct diagnosis, quantitative physiological classification, and potential treatment. Angina without angiographic stenosis is associated with abnormal quantitative perfusion with rare, but instructive, exceptions. However, microvascular dysfunction without angina is common, particularly associated with risk factors. Reduced subendocardial/epicardial relative activity is common with diffuse coronary artery disease without focal stenosis with or without angina depending on the severity of reduced subendocardial perfusion. Precision quantitative myocardial perfusion in 5,900 cases objectively classifies angina with no angiographic stenosis into 4 categories: subendocardial ischemia due to diffuse coronary artery disease (most common), overlooked stenosis, diffuse microvascular dysfunction due to risk factors or specific microvasculopathies, and nonischemic cardiac pain mechanisms (rare), or some mix of these prototypes, of which 95% associate with risk factors, or subclinical or clinically manifest coronary atherosclerosis needing vigorous risk factor treatment.

Article, see p 24 Nitroglycerin (NTG) was invented in 1847 and used for angina pectoris or heart failure since 1879 as reviewed by Asrress et al1 in the current issue of Circulation . An extensive literature shows that NTG lowers blood pressure, vasodilates epicardial coronary arteries, and in experimental models increases coronary blood flow to the subendocardium. What is new about this ancient heart medication documented by an enormous literature that merits publication in Circulation now? The report by Asrress et al1 details physiological mechanisms for angina relief by NTG epitomizing the evolution of clinical coronary physiology in 2 ways. First, it characterizes intracoronary physiological pressure/flow behavior of coronary stenosis during exercise before and after NTG for the first time, thereby explaining physiological consequences directly related to angina relief. Second, viewed analytically, the data in this article provide the basis for a substantial mechanistic and clinical conceptual leap beyond relief of angina caused by coronary stenosis. This conceptual leap integrates the larger generalized mechanisms of subendocardial ischemia because of any cause, such as severe aortic stenosis, ventricular hypertrophy, or small vessel disease, all without epicardial stenosis, or because of hard exercise with only mild to moderate stenosis. How does subendocardial ischemia relate to fractional flow reserve (FFR), which is now a severity standard for guiding revascularization, or relate to mortality risk, which has not been definitively reduced by revascularization in randomized trials? ### Coronary Physiology Background Understanding this article and its implications requires a brief historical snapshot of NTG-related coronary physiology. Figure summarizes proposed mechanisms for NTG relief of angina over 42 years from initial experimental subendocardial ischemia in 19752,3 to coronary pressure gradient-flow definition of physiological severity in 19784,5 to clinical coronary angiograms in 19896 to clinical coronary pressure flow velocity measurements during exercise …

Objective We propose a novel technique called pressure-bounded coronary flow reserve (pb-CFR) and demonstrate its application to the randomized DEFER trial. Background Intracoronary flow reserve assessment remains underutilized relative to pressure measurements partly due to less robust tools. Methods While rest and hyperemic intracoronary pressure measurements cannot quantify CFR exactly, they do provide upper and lower bounds. We validated pb-CFR invasively against traditional CFR, then applied it to high fractional flow reserve (FFR ≥ 0.75) lesions in DEFER randomized to revascularization or medical therapy. Results pb-CFR showed an 84.4% accuracy to predict invasive CFR

The purpose of this study was to utilize simulated data based on an ongoing randomized clinical trial (RCT) to evaluate the effects of treatment switching with randomization as an instrumental variable (IV) at differing levels of treatment crossovers, for continuous and binary outcomes. Data were analyzed using IV, intent-to-treat (ITT), and per protocol (PP) methods. The IV method performed the best, since it provided the most unbiased point estimates, and it had equal or higher power and higher coverage probabilities compared to the ITT estimates, and because a PP analysis can be biased due to its exclusion of non-compliant patients.

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.

Rationale We aimed to define the impact of variable arterial input function on myocardial perfusion severity that may misguide interventional decisions and relates to limited capacity of 3D PET for high-count arterial input function of standard bolus R-82. Methods We used GE Discovery-ST 16 slice PET-CT, serial 2D and 3D acquisitions of variable Rb-82 dose in a dynamic circulating arterial function model, static resolution and uniformity phantoms, and in patients with dipyridamole stress to quantify per-pixel rest and stress cc·min−1·g−1, CFR and CFC with (+) and (−) 10% simulated change in arterial input. Results For intermediate, border zone severity of stress perfusion, CFR and CFC comprising 7% of 3987 cases, simulated arterial input variability of ± 10% may cause over or underestimation of perfusion severity altering interventional decisions. In phantom tests, current 3D PET has capacity for quantifying high activity of arterial input and high-count per-pixel values of perfusion metrics per artery or branches. Conclusions Accurate, reproducible arterial input function is essential for at least 7% of patients at thresholds of perfusion severity for optimally guiding interventions and providing high-activity regional per-pixel perfusion metrics by 3D PET for displaying complex quantitative perfusion readily understood (“owned”) by interventionalists to guide procedures.

Background: Potentially some patients have symptoms that arise from their low-gradient aortic valve stenosis (AS). Comprehensive valve physiology with dobutamine stress remains incompletely characterized in this population. Methods: A cohort of 18 subjects with low-gradient AS underwent graded dobutamine infusion with invasive assessment using 0.014” pressure wires. A subset of 4 subjects received thermodilution cardiac output assessment at each stage. Results: Peak dobutamine hemodynamics could not be predicted from clinical or baseline parameters, reflecting statistically the physiologic heterogeneity of the measured pressure loss versus flow curves. While 0 subjects had a baseline aortic/left ventricular pressure ratio during ejection Conclusion: For low-gradient AS, the hemodynamic changes from resting to peak dobutamine conditions cannot be predicted in advance due to pressure loss versus flow curve heterogeneity. A sizable minority of low-gradient AS reaches a severity during dobutamine stress equivalent to patients undergoing TAVI for established benefit. Whether this subset receives similar clinical advantage remains an unproven but natural hypothesis raised by our study.

In aortic stenosis (AS), a longstanding question revolves around mechanisms for ischemia in patients with angina but normal coronary arteries [(1)][1]. The debate has focused on competing theories of microvascular dysfunction (inability of the myocardium to reduce arteriolar resistance) versus blood