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1. Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices

Author

Lennert Minten, Johan Bennett, Hisao Otsuki, Kuniaki Takahashi, William F. Fearon, and Christophe Dubois

Subjects
aortic stenosis, aortic valve replacement, coronary artery disease, fractional flow reserve, iFR, nonhyperemic pressure ratios, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta‐analysis was to study immediate and long‐term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). Methods and Results Lesion‐specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long‐term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (−0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long‐term after TAVR, FFR decreased significantly (−0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. Conclusions TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut‐offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.

Published
2024
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2. Myocardial Infarction Across COVID‐19 Pandemic Phases: Insights From the Veterans Health Affairs System

Author

Celina M. Yong, Laura Graham, Tariku J. Beyene, Shirin Sadri, Juliette Hong, Tom Burdon, William F. Fearon, Steven M. Asch, Mintu Turakhia, and Paul Heidenreich

Subjects
acute coronary syndrome, acute myocardial infarction, COVID‐19, non–ST‐segment–elevation myocardial infarction, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Cardiovascular procedural treatments were deferred at scale during the COVID‐19 pandemic, with unclear impact on patients presenting with non–ST‐segment–elevation myocardial infarction (NSTEMI). Methods and Results In a retrospective cohort study of all patients diagnosed with NSTEMI in the US Veterans Affairs Healthcare System from January 1, 2019 to October 30, 2022 (n=67 125), procedural treatments and outcomes were compared between the prepandemic period and 6 unique pandemic phases: (1) acute phase, (2) community spread, (3) first peak, (4) post vaccine, (5) second peak, and (6) recovery. Multivariable regression analysis was performed to assess the association between pandemic phases and 30‐day mortality. NSTEMI volumes dropped significantly with the pandemic onset (62.7% of prepandemic peak) and did not revert to prepandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention and coronary artery bypass grafting volumes declined proportionally. Compared with the prepandemic period, patients with NSTEMI experienced higher 30‐day mortality during Phases 2 and 3, even after adjustment for COVID‐19‐positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted odds ratio for Phases 2 and 3 combined, 1.26 [95% CI, 1.13–1.43], P

Published
2023
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3. Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post–Transcatheter Aortic Valve Implantation Death

Author

Andrew S. Perry, Shilin Zhao, Venkatesh Murthy, Deepak K. Gupta, William F. Fearon, Juyong B. Kim, Samir Kapadia, Dharam J. Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Ravinder R. Mallugari, Daniel E. Clark, Jay N. Patel, Holly Gonzales, Frederick G. Welt, Anthony A. Bavry, Megan Coylewright, Robert N. Piana, Anna Vatterott, Natalie Jackson, Robert E. Gerszten, Brian R. Lindman, Ravi Shah, and Sammy Elmariah

Subjects
aortic stenosis, metabolomics, outcomes, remodeling, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P

Published
2023
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4. Global Longitudinal Strain and Biomarkers of Cardiac Damage and Stress as Predictors of Outcomes After Transcatheter Aortic Valve Implantation

Author

Andrew S. Perry, Elliot J. Stein, Michael Biersmith, William F. Fearon, Sammy Elmariah, Juyong B. Kim, Daniel E. Clark, Jay N. Patel, Holly Gonzales, Michael Baker, Robert N. Piana, Ravinder R. Mallugari, Samir Kapadia, Dharam J. Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Frederick G. Welt, Anthony A. Bavry, Megan Coylewright, Deepak K. Gupta, Anna Vatterott, Natalie Jackson, Shi Huang, and Brian R. Lindman

Subjects
aortic stenosis, biomarkers, cardiac remodeling, echocardiography, global longitudinal strain, outcomes, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT‐proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT‐proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Published
2022
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5. Physiology-Based Revascularization

Author

Joo Myung Lee, MD, MPH, PhD, Seung Hun Lee, MD, PhD, Doosup Shin, MD, Ki Hong Choi, MD, Tim P. van de Hoef, MD, PhD, Hyun Kuk Kim, MD, PhD, Habib Samady, MD, PhD, Tsunekazu Kakuta, MD, PhD, Hitoshi Matsuo, MD, PhD, Bon-Kwon Koo, MD, PhD, William F. Fearon, MD, and Javier Escaned, MD, PhD

Subjects
fractional flow reserve, instantaneous wave-free ratio, nonhyperemic pressure ratios, percutaneous coronary intervention, prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

Published
2021
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6. Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis

Author

Elliot J. Stein, William F. Fearon, Sammy Elmariah, Juyong B. Kim, Samir Kapadia, Dharam J. Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Frederick G. Welt, Anthony A. Bavry, Megan Coylewright, Robert N. Piana, Ravinder R. Mallugari, Daniel E. Clark, Jay N. Patel, Holly Gonzales, Deepak K. Gupta, Anna Vatterott, Natalie Jackson, Shi Huang, and Brian R. Lindman

Subjects
biomarkers, left ventricular hypertrophy, mortality, NT‐proBNP, transcatheter aortic valve implantation, transcatheter aortic valve replacement, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Published
2022
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7. Fractional Flow Reserve and Instantaneous Wave‐Free Ratio Predict Pathological Wall Shear Stress in Coronary Arteries: Implications for Understanding the Pathophysiological Impact of Functionally Significant Coronary Stenoses

Author

Christopher C. Y. Wong, Ashkan Javadzadegan, Cuneyt Ada, Jerrett K. Lau, Ravinay Bhindi, William F. Fearon, Leonard Kritharides, Martin K. C. Ng, and Andy S. C. Yong

Subjects
fractional flow reserve, index of microcirculatory resistance, instantaneous wave‐free ratio, wall shear stress, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background The pathophysiological mechanism behind adverse outcomes associated with ischemia‐inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave‐free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (β) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (β=−0.44; 95% CI, −0.62 to −0.25; P

Published
2022
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9. Distance between valvular leaflet and coronary ostium predicting risk of coronary obstruction during TAVR

Author

Jun-Hyok Oh, Yuhei Kobayashi, Guson Kang, Takeshi Nishi, Martin J. Willemink, William F. Fearon, Michael Fischbein, Dominik Fleischmann, Alan C. Yeung, and Juyong Brian Kim

Subjects
TAVR, Coronary artery, Obstruction, Distance, Height, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The aim of this study was to evaluate the role of the distance between the aortic valve in projected position to the coronary ostium to determine risk of coronary artery obstruction after transcatheter aortic valve replacement (TAVR). Methods: An Expected Leaflet-to-ostium Distance (ELOD) was obtained on pre-TAVR planning computed tomography by subtracting leaflet thickness and the distances from the center to the annular rim at annulus level and from the center to the coronary ostium at mid-ostial level. Variables were compared between patients with and without coronary obstruction and the level of association between variables was assessed using log odds ratio (OR). Results: A total of 177 patients with 353 coronary arteries was analyzed. Mean annulus diameters (22.8 ± 2.8 mm and 23.4 ± 1.0 mm, p > 0.05) and mean sinus of Valsalva (SOV) diameters (31.2 ± 3.6 mm and 31.9 ± 3.6 mm, p > 0.05) were similar between patients with lower and higher coronary heights, respectively. There were three coronary obstruction cases. ELOD ≤ 2 mm in combination with leaflet length longer than mid-ostial height allowed for discrimination of cases with and without coronary obstruction. There was a significant association between coronary obstruction event and ELOD ≤ 2 mm (log OR = 6.180, p

Published
2021
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10. Association of microvascular dysfunction with clinical outcomes in patients with non-flow limiting fractional flow reserve after percutaneous coronary intervention

Author

Takeshi Nishi, Tadashi Murai, Katsuhisa Waseda, Atsushi Hirohata, Andy S.C. Yong, Martin K.C. Ng, Tetsuya Amano, Emanuele Barbato, Tsunekazu Kakuta, and William F. Fearon

Subjects
Microvascular dysfunction, Fractional flow reserve, The index of microcirculatory resistance, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: We sought to investigate prognostic implication of microvascular dysfunction as assessed by the index of microcirculatory index (IMR) in patients without residual obstructive CAD with non-flow limiting fractional flow reserve (FFR) (>0.80) following percutaneous coronary intervention (PCI). Methods: A total of 570 patients who had both post-PCI FFR and IMR values were included in the present analysis; of these, 65 patients had FFR ≤ 0.80 and 505 had FFR > 0.80. Of the 505 patients with FFR > 0.80, 137 had high IMR and 368 had low IMR. The primary outcome of the present analysis is a composite of all-cause death, spontaneous myocardial infarction, or target-vessel revascularization. Impaired microvascular function was defined as IMR ≥ 25 (high IMR). Results: During a median follow-up duration of 4.0 years, those with FFR > 0.80 and low IMR demonstrated lower rate or primary outcome event than those with FFR ≤ 0.80 (hazard ratio 0.49 [95% confidence interval 0.27–0.92], p = 0.026) and those with FFR > 0.80 and high IMR (hazard ratio 1.60 [0.99–2.16], p = 0.056). The patients with FFR > 0.80 and IMR ≥ 25 had similar rate of primary outcome event compared with those with FFR ≤ 0.80 (p = 0.49). Conclusion: Microvascular dysfunction following PCI is not rare and is associated with adverse events even in the setting of a non-flow limiting FFR; these results suggest that when performing coronary physiologic assessment following PCI, interrogating not only the epicardial vessel, but also the microvasculature is useful for the risk stratification in patients undergoing PCI.

Published
2021
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11. Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction

Author

Thomas H. Schindler, William F. Fearon, Matthieu Pelletier-Galarneau, Giuseppe Ambrosio, Udo Sechtem, Terrence D. Ruddy, Krishna K. Patel, Deepak L. Bhatt, Timothy M. Bateman, Henry Gewirtz, Jamshid Shirani, Juhani Knuuti, Robert J. Gropler, Panithaya Chareonthaitawee, Riemer H.J.A. Slart, Stephan Windecker, Philipp A. Kaufmann, Maria R. Abraham, Viviany R. Taqueti, Thomas J. Ford, Paolo G. Camici, Heinrich R. Schelbert, and Vasken Dilsizian

Subjects
Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Published
2023

12. Atrial Fibrillation Is Associated With Mortality in Intermediate Surgical Risk Patients With Severe Aortic Stenosis: Analyses From the PARTNER 2A and PARTNER S3i Trials

Author

Michael I. Brener, Isaac George, Ioanna Kosmidou, Tamim Nazif, Zixuan Zhang, Jose M. Dizon, Hasan Garan, S. Chris Malaisrie, Raj Makkar, Michael Mack, Wilson Y. Szeto, William F. Fearon, Vinod H. Thourani, Martin B. Leon, Susheel Kodali, and Angelo B. Biviano

Subjects
aortic stenosis, atrial fibrillation, transcatheter aortic valve replacement, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background The impact of atrial fibrillation (AF) in intermediate surgical risk patients with severe aortic stenosis who undergo either transcatheter or surgical aortic valve replacement (AVR) is not well established. Methods and Results Data were assessed in 2663 patients from the PARTNER (Placement of Aortic Transcatheter Valve) 2A or S3i trials. Analyses grouped patients into 3 categories according to their baseline and discharge rhythms (ie, sinus rhythm [SR]/SR, SR/AF, or AF/AF). Among patients with transcatheter AVR (n=1867), 79.2% had SR/SR, 17.6% had AF/AF, and 3.2% had SR/AF. Among patients with surgical AVR (n=796), 71.7% had SR/SR, 14.1% had AF/AF, and 14.2% had SR/AF. Patients with transcatheter AVR in AF at discharge had increased 2‐year mortality (SR/AF versus SR/SR; hazard ratio [HR], 2.73; 95% CI, 1.68–4.44; P

Published
2021
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13. Global Fractional Flow Reserve Value Predicts 5‐Year Outcomes in Patients With Coronary Atherosclerosis But Without Ischemia

Author

Stephane Fournier, Carlos Collet, Panagiotis Xaplanteris, Frederik M. Zimmermann, Gabor G. Toth, Pim A. L. Tonino, Nico H. J. Pijls, Iginio Colaiori, Giuseppe Di Gioia, Emanuele Barbato, Peter Jüni, William F. Fearon, and Bernard De Bruyne

Subjects
coronary atherosclerosis, fractional flow reserve, percutaneous coronary intervention, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long‐term clinical outcome of patients with stable coronary artery disease but no ischemia‐inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all‐cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post–percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80–2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5‐year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log‐rank P=0.040). The higher 5‐year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log‐rank P=0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977–0.998; P=0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966–0.998; P=0.032), and revascularization (HR, 0.985; 95% CI, 0.972–0.999; P=0.040). Conclusions Even in the absence of ischemia‐producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5‐year follow‐up.

Published
2020
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14. Invasive physiological indices to determine the functional significance of coronary stenosis

Author

Firas R. AL-Obaidi, William F. Fearon, and Andy S.C. Yong

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Physiological measurements are now commonly used to assess coronary lesions in the cardiac catheterisation laboratory, and this practice is evidence-based and supported by clinical guidelines. Fractional flow reserve is currently the gold standard method to determine whether coronary lesions are functionally significant, and is used to guide revascularization. There are however several other physiological measurements that have been proposed as alternatives to the fractional flow reserve. This review aims to comprehensively discuss physiological indices that can be used in the cardiac catheterisation laboratory to determine the functional significance of coronary lesions. We will focus on their advantages and disadvantages, and the current evidence supporting their use. Keywords: Coronary physiology, Fractional flow reserve, Resting physiological indices, Coronary flow reserve

Published
2018
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15. Long-Term Outcomes of Early Coronary Artery Disease Testing After New-Onset Heart Failure

Author

Jimmy Zheng, Paul A. Heidenreich, Shun Kohsaka, William F. Fearon, and Alexander T. Sandhu

Subjects
Cardiology and Cardiovascular Medicine
Abstract

BACKGROUND: Coronary artery disease (CAD) testing remains underutilized in patients with newly diagnosed heart failure (HF). The longitudinal clinical impact of early CAD testing has not been well-characterized. We investigated changes in clinical management and long-term outcomes after early CAD evaluation in patients with incident HF. METHODS: We identified Medicare patients with incident HF from 2006 to 2018. The exposure variable was early CAD testing within 1 month of initial HF diagnosis. Covariate-adjusted rates of cardiovascular interventions after testing, including CAD-related management, were modeled using mixed-effects regression with clinician as a random intercept. We assessed mortality and hospitalization outcomes using landmark analyses with inverse probability-weighted Cox proportional hazards models. Falsification end points and mediation analysis were employed for bias assessment. RESULTS: Among 309 559 patients with new-onset HF without prior CAD, 15.7% underwent early CAD testing. Patients who underwent prompt CAD evaluation had higher adjusted rates of subsequent antiplatelet/statin prescriptions and revascularization, guideline-directed therapy for HF, and stroke prophylaxis for atrial fibrillation/flutter than controls. In weighted Cox models, 1-month CAD testing was associated with significantly reduced all-cause mortality (hazard ratio, 0.93 [95% CI, 0.91–0.96]). Mediation analyses indicated that ≈70% of this association was explained by CAD management, largely from new statin prescriptions. Falsification end points (outpatient diagnoses of urinary tract infection and hospitalizations for hip/vertebral fracture) were nonsignificant. CONCLUSIONS: Early CAD testing after incident HF was associated with a modest mortality benefit, driven mostly by subsequent statin therapy. Further investigation on clinician barriers to testing and treating high-risk patients may improve adherence to guideline-recommended cardiovascular interventions.

Published
2023

17. Diagnostic performance of fractional flow reserve derived from coronary angiography, intravascular ultrasound, and optical coherence tomography; a meta-analysis

Author

Tatsunori Takahashi, Doosup Shin, Toshiki Kuno, Joo Myung Lee, Azeem Latib, William F. Fearon, Akiko Maehara, and Yuhei Kobayashi

Subjects
Fractional Flow Reserve, Myocardial, Predictive Value of Tests, Coronary Stenosis, Humans, Coronary Artery Disease, Coronary Angiography, Cardiology and Cardiovascular Medicine, Coronary Vessels, Severity of Illness Index, Tomography, Optical Coherence, Ultrasonography, Interventional
Abstract

Little is known about the overall diagnostic performance of computational fractional flow reserve (FFR) derived from angiography (Angio-FFR), intravascular ultrasound (IVUS-FFR), and optical coherence tomography (OCT-FFR) to detect hemodynamically significant coronary artery disease. The present study aimed to evaluate the diagnostic performance of those novel physiologic indices using conventional FFR as the gold standard.PubMed and Embase were searched in September 2021 for a systematic review and meta-analysis of studies assessing the diagnostic performance of invasive imaging-derived FFR. The primary outcomes were the summary sensitivity, specificity, correlation coefficients of each index.A total of 6572 records were initially identified and 49 studies were included in the final analysis (7010 lesions from 36 studies for Angio-FFR, 305 lesions from 5 studies for IVUS-FFR, and 667 lesions from 8 studies for OCT-FFR). Invasive imaging-derived FFR had a high diagnostic performance to detect functionally significant coronary lesions using conventional FFR as the gold standard [Angio-FFR, sensitivity 0.87 (95% CI 0.84-0.89), specificity 0.93 (95% CI 0.910.95); IVUS-FFR, sensitivity 0.90 (95% CI 0.84-0.94), specificity 0.95 (95% CI 0.90-0.98); OCT-FFR, sensitivity 0.85 (95% CI 0.78-0.91), specificity 0.93 (95% CI 0.89-0.95)]. The summary correlation coefficients of Angio-, IVUS-, and OCT-FFRs with wire-based FFR were 0.83 (95% CI 0.80-0.85), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86), respectively.This meta-analysis demonstrated that computational FFR derived from invasive coronary imaging has clinically acceptable diagnostic performances irrespective of modalities, supporting their applicability to clinical practice.

Published
2022

18. Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols

Author

Tatsunori Takahashi, Bruce A. Samuels, Weijia Li, Manish A. Parikh, Janet Wei, Jeffery W. Moses, William F. Fearon, Timothy D. Henry, Jennifer A. Tremmel, and Yuhei Kobayashi

Subjects
Spasm, Meta-Analysis as Topic, Ventricular Fibrillation, Coronary Vasospasm, Humans, Coronary Angiography, Cardiology and Cardiovascular Medicine, Coronary Vessels, Acetylcholine
Abstract

Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm.We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols.PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock.A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 μg and 200 μg.Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.

Published
2022

19. Quality of Life After Fractional Flow Reserve–Guided PCI Compared With Coronary Bypass Surgery

Author

William F, Fearon, Frederik M, Zimmermann, Victoria Y, Ding, Jo M, Zelis, Zsolt, Piroth, Giedrius, Davidavicius, Samer, Mansour, Rajesh, Kharbanda, Nikolaos, Östlund-Papadogeorgos, Keith G, Oldroyd, Olaf, Wendler, Michael J, Reardon, Y Joseph, Woo, Alan C, Yeung, Nico H J, Pijls, Bernard, De Bruyne, Manisha, Desai, and Mark A, Hlatky

Subjects
Canada, Coronary Artery Disease, Angina Pectoris, Fractional Flow Reserve, Myocardial, Percutaneous Coronary Intervention, Treatment Outcome, surgical procedures, operative, Physiology (medical), Quality of Life, Humans, cardiovascular diseases, Coronary Artery Bypass, Cardiology and Cardiovascular Medicine, Aged
Abstract

Background: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG. Methods: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve–guided PCI. Quality of life was measured using the European Quality of Life–5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status. Results: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, –0.016 to 0.017]; P =0.946). The trajectory of EQ-5D during the 12 months differed ( P Conclusions: In the FAME 3 trial, quality of life after fractional flow reserve–guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02100722.

Published
2022

22. Racial Differences in the Incidence and Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement

Author

S. Christopher Malaisrie, Do-Yoon Kang, Euihong Ko, Eric Cantey, James D. Flaherty, Jung-Min Ahn, Sehee Kim, Suk Jung Choo, Hanbit Park, Dae-Hee Kim, Seung-Jung Park, Charles J. Davidson, Takeshi Nishi, Duk-Woo Park, Ho Jin Kim, Alan C. Yeung, William F. Fearon, Juyong Brian Kim, Sung-Cheol Yun, Seung-Ah Lee, and Joon Bum Kim

Subjects
medicine.medical_specialty, education.field_of_study, Transcatheter aortic, business.industry, medicine.medical_treatment, Incidence (epidemiology), Population, medicine.disease, Prosthesis, Stenosis, Valve replacement, Aortic valve stenosis, Internal medicine, medicine, Cardiology and Cardiovascular Medicine, education, business, Cohort study
Abstract

Objectives The aim of this study was to compare the incidence and prognostic significance of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) according to racial groups. Background PPM after TAVR may be of more concern in Asian populations considering their relatively small annular and valve sizes compared with Western populations. Methods TP-TAVR (Transpacific TAVR Registry) was an international multicenter cohort study of patients with severe aortic stenosis who underwent TAVR in the United States and South Korea from January 2015 to November 2019. PPM was defined as moderate (0.65-0.85 cm2/m2) or severe ( Results Among 1,101 eligible patients (533 Asian and 569 non-Asian), the incidence of PPM was significantly lower in the Asian population (33.6%; moderate, 26.5%; severe, 7.1%) than in the non-Asian population (54.5%; moderate, 29.8%; severe, 24.7%). The 1-year rate of the primary outcome was similar between the PPM and non-PPM groups (27.5% vs 28.1%; P = 0.69); this pattern was consistent between Asian (25.4% vs 25.2%; P = 0.31) and non-Asian (28.7% vs 32.1%; P = 0.97) patients. After multivariable adjustment, the risk for the primary outcome did not significantly differ between the PPM and non-PPM groups in the overall population (HR: 0.95; 95% CI: 0.74-1.21), in Asian patients (HR: 1.07; 95% CI: 0.74-1.55), and in non-Asian patients (HR: 0.86; 95% CI: 0.63-1.19). Conclusions In this study of patients with severe aortic stenosis who underwent TAVR, the incidence of PPM was significantly lower in Asian patients than in non-Asian patients. The 1-year risk for the primary composite outcome was similar between the PPM and non-PPM groups regardless of racial group. (Transpacific TAVR Registry [TP-TAVR]; NCT03826264 )

Published
2021

23. FFRCT Planner

Author

William F. Fearon and Rushi V. Parikh

Subjects
Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Published
2022

24. Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function

Author

Jerrett K. Lau, Probal Roy, Ashkan Javadzadegan, Abouzar Moshfegh, William F. Fearon, Martin Ng, Harry Lowe, David Brieger, Leonard Kritharides, and Andy S. Yong

Subjects
coronary flow reserve, coronary physiology, microcirculation, microcirculatory resistance, remote ischemic preconditioning, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Remote ischemic preconditioning (RIPC) attenuates myocardial damage during elective and primary percutaneous coronary intervention. Recent studies suggest that coronary microcirculatory function is an important determinant of clinical outcome. The aim of this study was to assess the effect of RIPC on markers of microcirculatory function. Methods and Results Patients referred for cardiac catheterization and fractional flow reserve measurement were randomized to RIPC or sham. Operators and patients were blinded to treatment allocation. Comprehensive physiological assessments were performed before and after RIPC/sham including the index of microcirculatory resistance and coronary flow reserve after intracoronary glyceryl trinitrate and during the infusion of intravenous adenosine. Thirty patients were included (87% male; mean age: 63.1±10.0 years). RIPC and sham groups were similar with respect to baseline characteristics. RIPC decreased the calculated index of microcirculatory resistance (median, before RIPC: 22.6 [interquartile range [IQR]: 17.9–25.6]; after RIPC: 17.5 [IQR: 14.5–21.3]; P=0.007) and increased coronary flow reserve (2.6±0.9 versus 3.8±1.7, P=0.001). These RIPC‐mediated changes were associated with a reduction in hyperemic transit time (median: 0.33 [IQR: 0.26–0.40] versus 0.25 [IQR: 0.20–0.30]; P=0.010). RIPC resulted in a significant decrease in the calculated index of microcirculatory resistance compared with sham (relative change with treatment [mean±SD] was −18.1±24.8% versus +6.1±37.5; P=0.047) and a significant increase in coronary flow reserve (+41.2% [IQR: 20.0–61.7] versus −7.8% [IQR: −19.1 to 10.3]; P

Published
2018
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27. Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function

Author

Nico H.J. Pijls, Alessandro Candreva, Daniëlle C J Keulards, Jeroen Sonck, Annemiek De Vos, Emanuele Gallinoro, Pim A.L. Tonino, Carlos Collet, Jozef Bartunek, Emanuele Barbato, William F. Fearon, Marc Vanderheyden, Bernard De Bruyne, Marcel van 't Veer, Eric Wyffels, Mohamed El Farissi, Stephane Fournier, and Olivier Muller

Subjects
medicine.medical_specialty, business.industry, Coronary flow reserve, Fractional flow reserve, Confidence interval, Microvascular resistance, Flow velocity, Internal medicine, medicine, Cardiology, Cardiology and Cardiovascular Medicine, business, Myocardial mass, Coronary flow
Abstract

The need for a quantitative and operator-independent assessment of coronary microvascular function is increasingly recognized. We propose the theoretical framework of microvascular resistance reserve (MRR) as an index specific for the microvasculature, independent of autoregulation and myocardial mass, and based on operator-independent measurements of absolute values of coronary flow and pressure. In its general form, MRR equals coronary flow reserve (CFR) divided by fractional flow reserve (FFR) corrected for driving pressures. In 30 arteries, pressure, temperature, and flow velocity measurements were obtained simultaneously at baseline (BL), during infusion of saline at 10 mL/min (rest) and 20 mL/min (hyperemia). A strong correlation was found between continuous thermodilution-derived MRR and Doppler MRR (r = 0.88; 95% confidence interval: 0.72-0.93; P

Published
2021

28. CTA pulmonary artery enlargement in patients with severe aortic stenosis: Prognostic impact after TAVR

Author

Domenico Mastrodicasa, Michael P. Fischbein, William F. Fearon, Kegan J. Moneghetti, Juyong Brian Kim, Eva Maret, Martin J. Willemink, Valery Turner, Myriam Amsallem, Francois Haddad, Yukari Kobayashi, D. Craig Miller, Takeshi Nishi, Anson M. Lee, Marina Codari, Dominik Fleischmann, Anna M. Sailer, Virginia Hinostroza, Ayman Jubran, A.C. Watkins, and Alan C. Yeung

Subjects
medicine.medical_specialty, Computed Tomography Angiography, Kaplan-Meier Estimate, Pulmonary Artery, 030204 cardiovascular system & hematology, Severity of Illness Index, Article, 030218 nuclear medicine & medical imaging, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, medicine.artery, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Retrospective Studies, Computed tomography angiography, medicine.diagnostic_test, business.industry, Hazard ratio, Aortic Valve Stenosis, Prognosis, medicine.disease, Pulmonary hypertension, Stenosis, Treatment Outcome, Aortic Valve, Aortic valve stenosis, Pulmonary artery, Ventricular pressure, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

BACKGROUND: Identifying high-risk patients who will not derive substantial survival benefit from TAVR remains challenging. Pulmonary hypertension is a known predictor of poor outcome in patients undergoing TAVR and correlates strongly with pulmonary artery (PA) enlargement on CTA. We sought to evaluate whether PA enlargement, measured on pre-procedural computed tomography angiography (CTA), is associated with 1-year mortality in patients undergoing TAVR. METHODS: We retrospectively included 402 patients undergoing TAVR between July 2012 and March 2016. Clinical parameters, including Society of Thoracic Surgeons (STS) score and right ventricular systolic pressure (RVSP) estimated by transthoracic echocardiography were reviewed. PA dimensions were measured on pre-procedural CTAs. Association between PA enlargement and 1-year mortality was analyzed. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: The median follow-up time was 433 (interquartiles 339–797) days. A total of 56/402 (14%) patients died within 1 year after TAVR. Main PA area (area-MPA) was independently associated with 1-year mortality (hazard ratio per standard deviation equal to 2.04 [95%-confidence interval (CI) 1.48–2.76], p < 0.001). Area under the curve (95%-CI) of the clinical multivariable model including STS-score and RVSP increased slightly from 0.67 (0.59–0.75) to 0.72 (0.72–0.89), p = 0.346 by adding area-MPA. Although the AUC increased, differences were not significant (p = 0.346). Kaplan-Meier analysis showed that mortality was significantly higher in patients with a pre-procedural non-indexed area-MPA of ≥7.40 cm(2) compared to patients with a smaller area-MPA (mortality 23% vs. 9%; p < 0.001). CONCLUSIONS: Enlargement of MPA on pre-procedural CTA is independently associated with 1-year mortality after TAVR.

Published
2021

29. Impact of Serial Coronary Stenoses on Various Coronary Physiologic Indices

Author

Jung-Min Ahn, Takaharu Nakayoshi, Takehiro Hashikata, Kuninobu Kashiyama, Hiroyuki Arashi, Jihoon Kweon, Marcel van’t Veer, Jennifer Lyons, William F. Fearon, Eindhoven MedTech Innovation Center, Cardiovascular Biomechanics, and Immunoengineering

Subjects
Pathologic, Fractional Flow Reserve, Myocardial/physiology, Swine, Coronary Stenosis, Coronary Vessels/diagnostic imaging, Constriction, Pathologic, Coronary Angiography, Coronary Vessels, Constriction, Severity of Illness Index, Fractional Flow Reserve, Myocardial, Treatment Outcome, serial coronary stenoses, Animals, Female, Myocardial/physiology, hyperemia, Cardiology and Cardiovascular Medicine, fractional flow reserve, instantaneous wave free ratio, Coronary Stenosis/diagnosis, tandem lesions
Abstract

Background: Determining the functional significance of each individual coronary lesion in patients with serial coronary stenoses is challenging. It has been proposed that nonhyperemic pressure ratios, such as the instantaneous wave free ratio (iFR) and the ratio of resting distal to proximal coronary pressure (Pd/Pa) are more accurate than fractional flow reserve (FFR) because autoregulation should maintain stable resting coronary flow and avoid hemodynamic interdependence (cross-talk) that occurs during hyperemia. This study aimed to measure the degree of hemodynamic interdependence of iFR, resting Pd/Pa, and FFR in a porcine model of serial coronary stenosis. Methods: In 6 anesthetized female swine, 381 serial coronary stenoses were created in the left anterior descending artery using 2 balloon catheters. The degree of hemodynamic interdependence was calculated by measuring the absolute changes in iFR, resting Pd/Pa, and FFR across the fixed stenosis as the severity of the other stenosis varied. Results: The hemodynamic interdependence of iFR, resting Pd/Pa, and FFR was 0.039±0.048, 0.021±0.026, and 0.034±0.034, respectively (all P P P Conclusions: When assessing serial coronary stenoses, nonhyperemic pressure ratios are affected by hemodynamic interdependence. When the functional significance of serial coronary stenoses is severe, the effect is similar to that which is seen with FFR.

Published
2022

32. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C 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Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, 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Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M 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Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020

33. Physiology-Based Revascularization

Author

Doosup Shin, Habib Samady, Bon-Kwon Koo, Javier Escaned, Tsunekazu Kakuta, Hitoshi Matsuo, Hyun Kuk Kim, Seung-Hun Lee, Joo Myung Lee, Ki Hong Choi, William F. Fearon, and Tim P. van de Hoef

Subjects
medicine.medical_specialty, Standard of care, business.industry, medicine.medical_treatment, percutaneous coronary intervention, Atherosclerotic disease, Percutaneous coronary intervention, Fractional flow reserve, instantaneous wave-free ratio, Revascularization, nonhyperemic pressure ratios, RC666-701, Internal medicine, medicine, Cardiology, Diseases of the circulatory (Cardiovascular) system, prognosis, Instantaneous wave-free ratio, fractional flow reserve, business
Abstract

Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

Published
2021

34. Deep learning for prediction of fractional flow reserve from resting coronary pressure curves

Author

Ivo Everts, Thomas P Mast, Colin Berry, Pim A.L. Tonino, Frederik M. Zimmermann, Marcel van 't Veer, William F. Fearon, Bernard De Bruyne, Barry Hennigan, Nils P. Johnson, Daniel T. Johnson, Keith G. Oldroyd, Nico H.J. Pijls, Eindhoven MedTech Innovation Center, and Cardiovascular Biomechanics

Subjects
Stable angina, Cardiac Catheterization, Experimental Research, Coronary Vessels/diagnostic imaging, Fractional flow reserve, Coronary Angiography, Convolutional neural network, Severity of Illness Index, Deep Learning, Predictive Value of Tests, Artificial Intelligence, Statistics, Post-hoc analysis, Medicine, Humans, Myocardial, Innovation, Coronary Stenosis/diagnosis, Artificial neural network, business.industry, Deep learning, Coronary Stenosis, Reproducibility of Results, Coronary Vessels, Fractional Flow Reserve, Myocardial, Recurrent neural network, Predictive value of tests, Cohort, Artificial intelligence, Cardiology and Cardiovascular Medicine, business
Abstract

Background: It would be ideal for a non-hyperaemic index to predict fractional flow reserve (FFR) more accurately, given FFR's extensive validation in a multitude of clinical settings. Aims: The aim of this study was to derive a novel non-hyperaemic algorithm based on deep learning and to validate it in an internal validation cohort against FFR. Methods: The ARTIST study is a post hoc analysis of three previously published studies. In a derivation cohort (random 80% sample of the total cohort) a deep neural network was trained (deep learning) with paired examples of resting coronary pressure curves and their FFR values. The resulting algorithm was validated against unseen resting pressure curves from a random 20% sample of the total cohort. The primary endpoint was diagnostic accuracy of the deep learning-derived algorithms against binary FFR ≤0.8. To reduce the variance in the precision, we used a fivefold cross-validation procedure. Results: A total of 1,666 patients with 1,718 coronary lesions and 2,928 coronary pressure tracings were included. The diagnostic accuracy of our convolutional neural network (CNN) and recurrent neural networks (RNN) against binary FFR ≤0.80 was 79.6±1.9% and 77.6±2.3%, respectively. There was no statistically significant difference between the accuracy of our neural networks to predict binary FFR and the most accurate non-hyperaemic pressure ratio (NHPR). Conclusions: Compared to standard derivation of resting pressure ratios, we did not find a significant improvement in FFR prediction when resting data are analysed using artificial intelligence approaches. Our findings strongly suggest that a larger class of hidden information within resting pressure traces is not the main cause of the known disagreement between resting indices and FFR. Therefore, if clinicians want to use FFR for clinical decision making, hyperaemia induction should remain the standard practice.

Published
2021

35. Can We Predict Rejection Early After Heart Transplantation?

Author

Hannah A. Valantine and William F Fearon

Subjects
Heart transplantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine.disease, Transplant rejection, Coronary circulation, medicine.anatomical_structure, Coronary Circulation, Physiology (medical), Internal medicine, medicine, Cardiology, Heart Transplantation, Humans, Cardiology and Cardiovascular Medicine, business
Published
2021

36. The relationship between coronary artery distensibility and fractional flow reserve.

Author

Andy S C Yong, Ashkan Javadzadegan, William F Fearon, Abouzar Moshfegh, Jerrett K Lau, Stephen Nicholls, Martin K C Ng, and Leonard Kritharides

Subjects
Medicine, Science
Abstract

Discordance between angiography-based anatomical assessment of coronary stenosis severity and fractional flow reserve (FFR) has been attributed to several factors including lesion length and irregularity, and the myocardial territory supplied by the target vessel. We sought to examine if coronary arterial distensibility is an independent contributor to this discordance. There were two parts to this study. The first consisted of "in silico" models of 26 human coronary arteries. Computational fluid dynamics-derived FFR was calculated for fully rigid, partially distensible and fully distensible models of the 26 arteries. The second part of the study consisted of 104 patients who underwent coronary angiography and FFR measurement. Distensibility at the lesion site (DistensibilityMLA) and for the reference vessel (DistensibilityRef) was determined by analysing three-dimensional angiography images during end-systole and end-diastole. Computational fluid dynamics-derived FFR was 0.67±0.19, 0.70±0.18 and 0.75±0.17 (P

Published
2017
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37. Coronary Computed Tomography Angiography in Diagnosing Obstructive Coronary Artery Disease in Patients with Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Author

Valery Turner, Domenico Mastrodicasa, Simon Winther, Jane C. Tan, William F. Fearon, Dominik Fleischmann, Xingxing S. Cheng, and Suman S Mohanty

Subjects
medicine.medical_specialty, Computed Tomography Angiography, Urology, medicine.medical_treatment, Population, Coronary Artery Disease, Disease, Coronary Angiography, Coronary artery disease, Renal Dialysis, medicine, Humans, Renal Insufficiency, Chronic, education, Dialysis, Kidney transplantation, education.field_of_study, business.industry, Coronary computed tomography angiography, medicine.disease, Meta-analysis, Radiology, Cardiology and Cardiovascular Medicine, business, Research Article, Kidney disease
Abstract

Introduction: Coronary computed tomography angiography (CCTA) is emerging as an important noninvasive testing modality for coronary angiography. The performance characteristic of CCTA in patients with advanced kidney disease is unknown. Methods: We performed a systematic review and meta-analysis of studies specifically investigating the sensitivity and specificity of CCTA compared to coronary angiogram as a reference standard in patients with advanced kidney disease, defined as dialysis dependence or nearing kidney transplantation. Two independent investigators assessed studies for inclusion/exclusion, quality, and characteristics, while a third investigator adjudicated. Results: We identified 4 studies including a total of 217 patients, of whom 159 were dialysis dependent. Three of the 4 studies had a high risk of bias in patient selection and study flow, while 1 study rated low in all areas of bias. The studies were heterogeneous in their patient selection and CCTA protocol but consistent in their definition of obstructive coronary artery disease. The pooled sensitivity and specificity for CCTA were 0.96 (0.87–0.99) and 0.66 (0.57–0.74), respectively. When we restricted the analysis to dialysis-dependent patients, the pooled sensitivity and specificity for CCTA were 0.99 (0.74–1.00) and 0.67 (0.49–0.82), respectively. Conclusions: Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.

Published
2020

38. Variability in Coronary Artery Disease Testing for Patients with New-Onset Heart Failure

Author

Jimmy Zheng, Paul A. Heidenreich, Shun Kohsaka, William F. Fearon, and Alexander T. Sandhu

Subjects
Male, Heart Failure, Outpatients, Myocardial Ischemia, Humans, Coronary Artery Disease, Medicare, Cardiology and Cardiovascular Medicine, United States, Article, Aged
Abstract

BACKGROUND: Coronary artery disease (CAD) is the most common cause of new-onset heart failure (HF). Although guidelines recommend ischemic evaluation in this population, testing has historically been underutilized. OBJECTIVES: This study aimed to identify contemporary trends in CAD testing for new-onset HF patients, particularly after publication of the Surgical Treatment for Ischemic Heart Failure Extension Study (STICHES), and to characterize geographic and clinician-level variability in testing patterns. METHODS: We determined the proportion of incident HF patients who received CAD testing from 2004–2019 using an administrative claims database covering commercial insurance and Medicare. We identified demographic and clinical predictors of CAD testing during the 90 days before and after initial diagnosis. Patients were grouped by their county of residence to assess national variation. Patients were then linked to their primary care physician and/or cardiologist to evaluate variation across clinicians. RESULTS: Among 558,322 new-onset HF patients, 34.8% underwent CAD testing and 9.3% underwent revascularization. After multivariable adjustment, patients who underwent CAD testing were more likely to be younger, male, diagnosed in an acute care setting, and have systolic dysfunction or recent cardiogenic shock. Incidence of CAD testing remained flat without significant change post-STICHES. Covariate-adjusted testing rates varied from 20–45% across counties. The likelihood of testing was higher among patients co-managed by a cardiologist (adjusted OR 5.12, 95% CI 4.98–5.27) but varied substantially across cardiologists (IQR: 50.9–62.4%). CONCLUSIONS: Most new-onset HF patients across inpatient and outpatient settings did not receive timely testing for CAD. Substantial variability in testing persists across regions and clinicians.

Published
2022

39. FFR

Author

William F, Fearon and Rushi V, Parikh

Subjects
Fractional Flow Reserve, Myocardial, Percutaneous Coronary Intervention, Computed Tomography Angiography, Predictive Value of Tests, Coronary Stenosis, Humans, Coronary Artery Disease, Coronary Angiography, Tomography, X-Ray Computed, Severity of Illness Index
Published
2022

40. Fractional Flow Reserve and 'Hard' Endpoints

Author

Hiroyuki Arashi and William F. Fearon

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, MEDLINE, Percutaneous coronary intervention, Fractional flow reserve, medicine.disease, Angina Pectoris, Fractional Flow Reserve, Myocardial, Coronary artery disease, Percutaneous Coronary Intervention, Internal medicine, medicine, Cardiology, Humans, Cardiology and Cardiovascular Medicine, business
Published
2020

41. Diagnostic Accuracy of Nonhyperemic Pressure Ratios Using a Pressure Sensing Microcatheter

Author

Hiroyuki Arashi, Yuhei Kobayashi, Matthew J. Price, Takeshi Nishi, Jeffrey W. Chambers, Arnold H. Seto, Ian J. Sarembock, Ganesh Raveendran, Allen Jeremias, and William F. Fearon

Subjects
medicine.medical_specialty, Myocardial ischemia, business.industry, medicine.medical_treatment, Pressure sensing, Percutaneous coronary intervention, Diagnostic accuracy, Fractional flow reserve, 030204 cardiovascular system & hematology, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Predictive value of tests, Internal medicine, medicine, Cardiology, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Cardiac Catheters
Abstract

Fractional flow reserve (FFR) measurement can identify coronary lesions responsible for myocardial ischemia that will benefit most from percutaneous coronary intervention. Measuring FFR remains underused in clinical practice in part because of issues related to the pressure wire (e.g., crossing of

Published
2020

42. Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement

Author

Robert W. Hodson, Maria Alu, Todd M. Dewey, Howard C. Herrmann, Raj Makkar, Rebecca T. Hahn, Wilson Y. Szeto, Sung-Han Yoon, Wael A. Jaber, Philippe Pibarot, Samir R. Kapadia, Vasilis Babaliaros, Ke Xu, D. Craig Miller, Alan Zajarias, Erin Rogers, Martin B. Leon, Mathew R. Williams, Jaime Wheeler, Craig R. Smith, Dean J. Kereiakes, Mark J. Russo, Brian Whisenant, John G. Webb, William F. Fearon, Alfredo Trento, David L. Brown, David J. Cohen, Susheel Kodali, Kevin L. Greason, Vinod H. Thourani, Lowell P. Satler, Lars G. Svensson, and Michael J. Mack

Subjects
Aortic valve, medicine.medical_specialty, Intention-to-treat analysis, business.industry, General Medicine, 030204 cardiovascular system & hematology, Aortic Valve Insufficiency, medicine.disease, law.invention, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Randomized controlled trial, Aortic valve replacement, law, Aortic valve stenosis, cardiovascular system, medicine, 030212 general & internal medicine, business, Stroke, Cohort study
Abstract

Background There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve r...

Published
2020

43. Diagnostic Performance of Angiogram-Derived Fractional Flow Reserve

Author

Ran Kornowski, Stephan Achenbach, Hitoshi Matsuo, Thomas Engstrøm, William F. Fearon, Bernard De Bruyne, and Guy Witberg

Subjects
Coronary angiography, medicine.medical_specialty, business.industry, Fractional flow reserve, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Pooled analysis, Guidelines recommendations, Internal medicine, Cohort, medicine, Cardiology, Cutoff, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Prospective cohort study, Reference standards
Abstract

Objectives This study sought to assess the diagnostic performance of FFRangio (CathWorks, Kfar Saba, Israel), an angiogram-derived fractional flow reserve (FFR) technology. Background Despite practice guidelines recommendations, the use of coronary physiologic assessment in daily practice remains low for patients undergoing coronary angiography. Angiogram-derived FFR technologies have the potential to promote the integration of physiologic assessment in daily practice. Methods The study performed an analysis of pooled patient- and lesion-level data from 5 prospective cohort studies that examined the diagnostic performance of FFRangio compared with the reference standard wire-based FFR. Results A total of 700 lesions from 588 patients were analyzed. Mean age was 65 years, 71% were men, and 40% presented with acute coronary syndromes. Mean FFR and FFRangio were 0.81 ± 0.12 and 0.81 ± 0.11, with 31.6% and 31.4% of lesions were in the 0.75 to 0.85 range, respectively. When using a binary cutoff FFR value of 0.80, FFRangio showed a sensitivity of 91%, a specificity of 94%, and a diagnostic accuracy of 93%. The mean difference between FFR and FFRangio was 0.00 ± 0.12. The correlation coefficient between FFR and FFRangio was 0.83 (p Conclusions In the largest reported cohort examining the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was robust and consistent across all patient and lesion subgroups. Additional studies are needed allow FFRangio and fulfill its potential expand the implementation of functional assessment of coronary lesions in routine clinical practice.

Published
2020

44. Fractional flow reserve–guided PCI as compared with coronary bypass surgery

Author

Filip Casselman, Kreton Mavromatis, Adel Aminian, Gintaras Kalinauskas, Victoria Y. Ding, Philip MacCarthy, Nawwar Al-Attar, Bernard De Bruyne, Nico H.J. Pijls, Oskar Angerås, Giedrius Davidavičius, Y. Joseph Woo, Di Lu, Petr Kala, Jan-Henk E. Dambrink, Nikolaos Östlund-Papadogeorgos, Michael J. Reardon, Laszlo Szekely, Jaydeep Sarma, Manisha Desai, Keith G. Oldroyd, Kenneth W. Mahaffey, Rajesh Kharbanda, Pim A.L. Tonino, Albert H.M. van Straten, Nils Witt, Nikola Jagic, Evald Høj Christiansen, Fame Study Investigators, Zsolt Piroth, William F Fearon, Mark A. Hlatky, Samer Mansour, Steven E S Miner, Alan C. Yeung, Yuhei Kobayashi, Frederik M. Zimmermann, Thomas Engstrøm, and Olaf Wendler

Subjects
Reoperation, Male, medicine.medical_specialty, CLINICAL-OUTCOMES, EVEROLIMUS-ELUTING STENTS, Coronary Artery Bypass/adverse effects, medicine.medical_treatment, Operative Time, UNIVERSAL DEFINITION, Fractional flow reserve, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, ANGIOGRAPHY, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Stroke, Coronary Stenosis/mortality, Percutaneous Coronary Intervention/adverse effects, Aged, FAME 3 TRIAL, GRAFT-SURGERY, business.industry, Cardiovascular Diseases/epidemiology, Hazard ratio, Percutaneous coronary intervention, General Medicine, Length of Stay, Middle Aged, medicine.disease, 3. Good health, Fractional Flow Reserve, Myocardial, surgical procedures, operative, Bypass surgery, Conventional PCI, Cardiology, REVASCULARIZATION, Female, Stents, business, INTERVENTION
Abstract

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Published
2022

45. Abstract 11935: The Index of Microcirculatory Resistance to Predict Subsequent Acute Cellular Rejection and Cardiac Events After Heart Transplantation

Author

Jung-Min Ahn, Frederik Zimmermann, Lars L Gullestad, Oskar Angerås, Kristjan Karason, Kristoffer Russell, Ketil Lunde, Kozo Okada, Helen Luikart, Kiran K Khush, Yasuhiro Honda, Nico Pijls, Sang Eun Lee, Jae-Joong Kim, Seung-jung Park, Ole-Geir Solberg, and William F Fearon

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Single center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute cellular rejection. Hypothesis: To validate whether IMR measured early after transplantation can predict subsequent acute cellular rejection and long-term outcome in a large multicenter cohort. Methods: From 5 international heart transplantation cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was biopsy-proven acute cellular rejection of grade 2 or 3 within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE, the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission due to a cardiac cause) at 10 years. Results: IMR was measured at a median of 7 weeks (interquartile range: 3 to 10 weeks) post-transplantation. Patients with acute cellular rejection grade 2 or 3 at the time of IMR assessment were excluded. At 1 year, the incidence of acute cellular rejection was 14.0%. IMR was associated proportionally with the risk of acute cellular rejection (per increase of 1-unit IMR; adjusted hazard ratio [aHR], 1.04; 95% confidence interval [CI], 1.01-1.06; P=0.002). The incidence of acute cellular rejection in patients with IMR ≥ 18 was 23.8%, while the incidence of acute cellular rejection in those with IMR < 18 was 5.5% (aHR, 4.09; 95% CI, 1.67-10.0; P=0.002). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-unit IMR; aHR, 1.03; 95% CI, 1.01-1.05; P=0.002). Conclusions: IMR measured early after heart transplantation is associated with subsequent acute cellular rejection at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized post-transplantation management.

Published
2021

46. Abstract 10288: Reduced Pulmonary Artery Distensibility: A Predictor of Persistent Pulmonary Hypertension and 2-Year Mortality Post-Transcatheter Aortic Valve Replacement in High-Risk Patients with Severe Aortic Stenosis

Author

Valery Turner, Eva Maret, Juyong B Kim, A Claire C Watkins, William F Fearon, Francois Haddad, Martin J Willemink, and Dominik Fleischmann

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Persistent pulmonary hypertension (PH) post-TAVR is a better predictor of poor outcome than pre-TAVR PH, possibly due to longstanding vascular damage involving loss of pulmonary artery (PA) elasticity. In this study we sought to evaluate whether PA distensibility (D PA ) measured on pre-procedural ECG-gated CTA is associated with persistent-PH and 2-year mortality after TAVR. Hypothesis: Reduced D PA is a predictor of persistent-PH and mortality post-TAVR. Methods: 336 patients undergoing TAVR between July 2012 and March 2016 were retrospectively included. All patients underwent retrospectively ECG-gated CTA of the chest, with reconstruction of 10 phases over the cardiac cycle (0%- 90% of the R-R interval) prior to TAVR. Patients were followed for all-cause mortality. Main pulmonary artery (MPA) area was measured at 20% (area-MPA 20 ) and 80% (area-MPA 80 ) of the R-R interval. D PA was calculated as follows: [(area-MPA 20 -area-MPA 80 )/area-MPA 20 ]%. Persistent-PH was defined as pre-TAVR RVSP>35mmHg which persisted >35mmHg in post-TAVR echocardiography. 2 groups were compared based on D PA Results: Median follow-up time was 413 (interquartiles 339-757) days. A total of 68 (20%) patients died within 2 years after TAVR and 183 (54%) had persistent-PH. Those with D PA PA >8%. Multivariable regression analyses adjusted for age, sex, STS-score, cardiac risk, frailty≥2 and NYHA≥III, showed that D PA PA PA ≥8% (mortality 28% vs 15%; log-rank p=0.003). Conclusion: D PA on pre-procedural CTA is independently associated with persistent-PH and two-year mortality in patients who undergo TAVR and could be a valuable parameter for risk stratification of TAVR candidates.

Published
2021

48. Microcirculatory Resistance Predicts Allograft Rejection and Cardiac Events After Heart Transplantation

Author

Jung-Min Ahn, Frederik M. Zimmermann, Lars Gullestad, Oskar Angerås, Kristjan Karason, Kristoffer Russell, Ketil Lunde, Kozo Okada, Helen Luikart, Kiran K. Khush, Yasuhiro Honda, Nico H.J. Pijls, Sang Eun Lee, Jae-Joong Kim, Seung-Jung Park, Ole-Geir Solberg, and William F. Fearon

Subjects
Graft Rejection, Male, Time Factors, Microcirculation, Middle Aged, Allografts, Coronary Angiography, Predictive Value of Tests, Coronary Circulation, Heart Transplantation, Humans, Female, Vascular Resistance, Prospective Studies, Cardiology and Cardiovascular Medicine, Follow-Up Studies
Abstract

Single-center data suggest that the index of microcirculatory resistance (IMR) measured early after heart transplantation predicts subsequent acute rejection.The goal of this study was to validate whether IMR measured early after transplantation can predict subsequent acute rejection and long-term outcome in a large multicenter cohort.From 5 international cohorts, 237 patients who underwent IMR measurement early after transplantation were enrolled. The primary outcome was acute allograft rejection (AAR) within 1 year after transplantation. A key secondary outcome was major adverse cardiac events (MACE) (the composite of death, re-transplantation, myocardial infarction, stroke, graft dysfunction, and readmission) at 10 years.IMR was measured at a median of 7 weeks (interquartile range: 3-10 weeks) post-transplantation. At 1 year, the incidence of AAR was 14.4%. IMR was associated proportionally with the risk of AAR (per increase of 1-U IMR; adjusted hazard ratio [aHR]: 1.04; 95% confidence interval [CI]: 1.02-1.06; p0.001). The incidence of AAR in patients with an IMR ≥18 was 23.8%, whereas the incidence of AAR in those with an IMR 18 was 6.3% (aHR: 3.93; 95% CI: 1.77-8.73; P = 0.001). At 10 years, MACE occurred in 86 (36.3%) patients. IMR was significantly associated with the risk of MACE (per increase of 1-U IMR; aHR: 1.02; 95% CI: 1.01-1.04; P = 0.005).IMR measured early after heart transplantation is associated with subsequent AAR at 1 year and clinical events at 10 years. Early IMR measurement after transplantation identifies patients at higher risk and may guide personalized posttransplantation management.

Published
2021

49. Association of microvascular dysfunction with clinical outcomes in patients with non-flow limiting fractional flow reserve after percutaneous coronary intervention

Author

Atsushi Hirohata, Tetsuya Amano, Andy S.C. Yong, Martin K.C. Ng, Takeshi Nishi, Tsunekazu Kakuta, Emanuele Barbato, Tadashi Murai, Katsuhisa Waseda, and William F. Fearon

Subjects
FFR, fractional flow reserve, medicine.medical_specialty, The index of microcirculatory resistance, medicine.medical_treatment, Fractional flow reserve, Revascularization, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Myocardial infarction, Adverse effect, MVD, microvascular dysfunction, Original Paper, PCI, percutaneous coronary intervention, business.industry, Hazard ratio, Percutaneous coronary intervention, medicine.disease, Confidence interval, Microvascular dysfunction, TVR, target vessel revascularization, RC666-701, Conventional PCI, MI, myocardial infarction, Cardiology, IMR, the index of microcirculatory index, Cardiology and Cardiovascular Medicine, business
Abstract

Background We sought to investigate prognostic implication of microvascular dysfunction as assessed by the index of microcirculatory index (IMR) in patients without residual obstructive CAD with non-flow limiting fractional flow reserve (FFR) (>0.80) following percutaneous coronary intervention (PCI). Methods A total of 570 patients who had both post-PCI FFR and IMR values were included in the present analysis; of these, 65 patients had FFR ≤ 0.80 and 505 had FFR > 0.80. Of the 505 patients with FFR > 0.80, 137 had high IMR and 368 had low IMR. The primary outcome of the present analysis is a composite of all-cause death, spontaneous myocardial infarction, or target-vessel revascularization. Impaired microvascular function was defined as IMR ≥ 25 (high IMR). Results During a median follow-up duration of 4.0 years, those with FFR > 0.80 and low IMR demonstrated lower rate or primary outcome event than those with FFR ≤ 0.80 (hazard ratio 0.49 [95% confidence interval 0.27–0.92], p = 0.026) and those with FFR > 0.80 and high IMR (hazard ratio 1.60 [0.99–2.16], p = 0.056). The patients with FFR > 0.80 and IMR ≥ 25 had similar rate of primary outcome event compared with those with FFR ≤ 0.80 (p = 0.49). Conclusion Microvascular dysfunction following PCI is not rare and is associated with adverse events even in the setting of a non-flow limiting FFR; these results suggest that when performing coronary physiologic assessment following PCI, interrogating not only the epicardial vessel, but also the microvasculature is useful for the risk stratification in patients undergoing PCI.

Published
2021

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