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1. Tandem lesions associate with angiographic progression of coronary artery stenoses

Author: Kyle B. Franke, Nicholas J. Montarello, Adam J. Nelson, Jessica A. Marathe, Dennis T.L. Wong, Rosanna Tavella, Margaret Arstall, Christopher Zeitz, Matthew I. Worthley, John F. Beltrame, and Peter J. Psaltis
Subjects: Atherosclerosis, Coronary artery disease, Quantitative coronary angiography, Plaque progression, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56–73) and the median interval between angiograms was 2.1 years (IQR 1.2–3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04–4.63, p
Published: 2024
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2. Angina and Non-Obstructive Coronary Artery (ANOCA) Patients with Coronary Vasomotor Disorders

Author: Sarena La, Rosanna Tavella, Jing Wu, Sivabaskari Pasupathy, Christopher Zeitz, Matthew Worthley, Ajay Sinhal, Margaret Arstall, John A. Spertus, and John F. Beltrame
Subjects: ANOCA, functional angiography, coronary vasomotor disorders, coronary artery spasm, coronary microvascular disease, Science
Abstract: Angina and Non-Obstructive Coronary Artery (ANOCA) patients often lack a clear explanation for their symptoms, and are frequently discharged with the label of “unspecified chest pain”, despite the availability of functional coronary angiography (provocative spasm and microvascular function testing) to identify potential underlying coronary vasomotor disorders. This study compared the outcomes of ANOCA patients with a coronary vasomotor disorder diagnosis post elective coronary angiography to patients discharged with unspecified chest pain. Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive symptomatic patients (n = 7555) from 2012 to 2018 underwent elective angiography; 30% had ANOCA (stenosis p < 0.001) and readmissions for chest pain (30% vs. 10%, p < 0.001) compared with those with unspecified chest pain. This real-world study emphasizes the importance of identifying high-risk ANOCA patients for personalized management to effectively address their symptoms.
Published: 2023
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3. Prognostic association of plasma NT-proBNP levels in patients with microvascular angina -A report from the international cohort study by COVADIS

Author: Akira Suda, Jun Takahashi, Maike Schwidder, Peter Ong, Daniel Ang, Colin Berry, Paolo G. Camici, Filippo Crea, Juan Carlos Kaski, Carl Pepine, Ornella Rimoldi, Udo Sechtem, Satoshi Yasuda, John F. Beltrame, C. Noel Bairey Merz, and Hiroaki Shimokawa
Subjects: Microvascular angina, Brain natriuretic peptides, NT-proBNP, Prognosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroudThe aim of this study was to assess the prognostic association of plasma levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) with clinical outcomes of patients with microvascular angina (MVA). Methods: In this international prospective cohort study of MVA by the Coronary Vasomotor Disorders International Study (COVADIS) group, we examined the association between plasma NT-proBNP levels and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. Results: We examined a total of 226 MVA patients (M/F 66/160, 61.9 ± 10.2 [SD] yrs.) with both plasma NT-proBNP levels and echocardiography data available at the time of enrolment. The median level of NT-proBNP level was 94 pg/ml, while mean left ventricular ejection fraction was 69.2 ± 10.9 % and E/e’ 10.7 ± 5.2. During follow-up period of a median of 365 days (IQR 365–482), 29 MACEs occurred. Receiver-operating characteristics curve analysis identified plasma NT-proBNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-proBNP level ≥ 78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95 % confidence interval (CI)] 3.11[1.14–8.49], P = 0.001). Accordingly, Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-proBNP ≥ 78 (log-rank test, P
Published: 2022
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4. The Association between Sleep Duration and Quality with Readmissions: An Exploratory Pilot-Study among Cardiology Inpatients

Author: Clementine Labrosciano, Rosanna Tavella, Amy Reynolds, Tracy Air, John F. Beltrame, Isuru Ranasinghe, and Robert J. T. Adams
Subjects: actigraphy, cardiology, inpatients, readmissions, Medicine
Abstract: Background: Readmissions within 30 days of discharge are prominent among patients with cardiovascular disease. Post hospital syndrome hypothesizes that sleep disturbance during the index admission contributes to an acquired transient vulnerability, leading to increased risk of readmission. This study evaluated the association of in-hospital sleep (a) duration and (b) quality with 30-day all-cause unplanned readmission. Methods: This prospective observational cohort study included patients admitted to the coronary care unit of a South Australian hospital between 2016–2018. Study participants were invited to wear an ActiGraph GT3X+ for the duration of their admission and for two weeks post-discharge. Validated sleep and quality of life questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), were administered. Readmission status and questionnaires were assessed at 30 days post-discharge via patient telephone interview and a review of hospital records. Results: The final cohort consisted of 75 patients (readmitted: n = 15, non-readmitted: n = 60), of which 72% were male with a mean age 66.9 ± 13.1 years. Total sleep time (TST), both in hospital (6.9 ± 1.3 vs. 6.8 ± 2.9 h, p = 0.96) and post-discharge (7.4 ± 1.3 h vs. 8.9 ± 12.6 h, p = 0.76), was similar in all patients. Patient’s perception of sleep, reflected by PSQI scores, was poorer in readmitted patients (9.13 ± 3.6 vs. 6.4 ± 4.1, p = 0.02). Conclusions: Although an association between total sleep time and 30-day readmission was not found, patients who reported poorer sleep quality were more likely to be readmitted within 30 days. This study also highlighted the importance of improving sleep, both in and out of the hospital, to improve the outcomes of cardiology inpatients.
Published: 2020
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5. Sex Differences in Incidence and Outcome of Out-of-Hospital Cardiac Arrest Within a Local Health Network

Author: Melanie R. Wittwer, Emily Aldridge, Cindy Hein, Mel Thorrowgood, Chris Zeitz, John F. Beltrame, and Margaret A. Arstall
Subjects: out-of-hospital cardiac arrest, sex, gender, outcomes - health care, aetiology (etiology), socioeconomic status, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: IntroductionSex and gender differences in presentation and characteristics of out-of-hospital cardiac arrest (OHCA) are established in cohorts with presumed cardiac aetiology but not non-cardiac etiology. This study investigated the effect of sex on incidence and outcome of OHCA according to presumed and adjudicated aetiology within a local health network.MethodsPopulation-based observational cohort study of emergency medical services (EMS) attended OHCAs within an Australian local health network. Cases identified from an EMS registry between 2012-2016 were linked to a hospital registry. Age-standardised incidence and baseline characteristics were stratified by sex for EMS-treated OHCA, non-EMS witnessed presumed cardiac and obvious non-cardiac sub-cohorts, and hospitalised cases. Logistic regression was used to explore the primary outcome of survival to hospital discharge.ResultsWe identified 2,024 EMS-attended and 780 EMS-treated OHCAs. The non-EMS witnessed sub-cohorts comprised 504 presumed cardiac and 168 obvious non-cardiac OHCAs. Adjudicated aetiology was recorded in 123 hospitalised cases. Age-standardised incidence for women was almost half that of men across all groups. Across cohorts, women were generally older and arrested with a non-shockable initial rhythm in an area of low socioeconomic status. There was no sex difference in the primary outcome for the main EMS-treated cohort or in the non-cardiac sub-cohorts. The sex difference in outcome in the presumed cardiac sub-cohort was not present after multivariable adjustment.ConclusionsThere are sex differences in incidence and outcome of EMS-treated OHCA that appear to be driven by differences in susceptibility to cardiac arrhythmias and underlying etiology, rather than treatment delays or disparities.
Published: 2022
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6. Transdiagnostic Cognitive-Behavioral Therapy for Depression and Anxiety Disorders in Cardiovascular Disease Patients: Results From the CHAMPS Pilot-Feasibility Trial

Author: Phillip J. Tully, Deborah A. Turnbull, John D. Horowitz, John F. Beltrame, Bernhard T. Baune, Shannon Sauer-Zavala, Harald Baumeister, Christopher G. Bean, Ronette B. Pinto, Suzie Cosh, and Gary A. Wittert
Subjects: depression, major depression (MDD), anxiety, anxiety disorders, cardiovascular disease, coronary heart disease, Psychiatry, RC435-571
Abstract: ObjectiveThe aim of the Cardiovascular Health in Anxiety and Mood Problems Study (CHAMPS) is to pilot the Unified Protocol (UP) for the transdiagnostic treatment of depression and anxiety disorders in patients recently hospitalized for cardiovascular diseases (CVDs) and evaluate the feasibility.MethodsThe present study is a controlled, block randomized pragmatic pilot-feasibility trial incorporating qualitative interview data, comparing UP (n = 9) with enhanced usual care (EUC, n = 10). Eligible trial participants had a recent CVD-cause admission and were above the severity threshold for depression or anxiety denoted by Patient Health Questionnaire (PHQ-9) total scores ≥10 and/or Generalized Anxiety Disorder (GAD-7) total scores ≥7 respectively on two occasions, and met criteria for one or more depression or anxiety disorders determined by structured clinical interview. Study outcomes were analyzed as intention-to-treat using linear mixed models and qualitative interview data were analyzed with content analysis.ResultsQuantitative and qualitative measured indicated acceptability of the transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders. Satisfaction with UP was comparable to antidepressant therapy and higher than general physician counseling. However, there were difficulties recruiting participants with current disorders and distress on two occasions. The UP was associated with a reduction in total number of disorders determined by blinded raters. Linear mixed models indicated that a significantly greater reduction in anxiety symptoms was evident in the UP group by comparison to the EUC group (GAD-7, p between groups = 0.011; Overall Anxiety Severity and Impairment Scale, p between groups = 0.013). Results favored the UP group by comparison to EUC for change over 6 months on measures of physical quality of life and harmful alcohol use. There was no difference between the two groups on changes in depression symptoms (PHQ-9), stress, metacognitive worry beliefs, physical activity, or adherence.DiscussionIn conclusion, this feasibility trial indicates acceptability of transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders that is tempered by difficulties with recruitment. Larger trials are required to clarify the efficacy of transdiagnostic depression and anxiety disorder CBT in populations with CVDs and depressive or anxiety disorders.Clinical Trial Registrationhttps://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12615000555550, identifier: ACTRN12615000555550.
Published: 2022
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7. Insights to advance our management of myocardial ischemia: From obstructive epicardial disease to functional coronary alterations

Author: C. Noel Bairey Merz, John F. Beltrame, Colin Berry, William E. Boden, Paolo G. Camici, Filippo Crea, Judith S. Hochman, Juan Carlos Kaski, Patrick T. O'Gara, Peter Ong, Carl J. Pepine, Hiroaki Shimokawa, Udo Sechtem, and Gregg W. Stone
Subjects: Coronary artery disease, Coronary microvascular dysfunction, Microvascular angina, Myocardial ischemia with no obstructive CAD (INOCA), Vasospastic angina, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Study objective: The Coronary Vasomotor Disorders International Study Group (COVADIS) invited leading experts to address strategies to enhance our clinical understanding of INOCA with an emphasis on the management of coronary vasomotor disorders. Design: Under-recognition of coronary vasomotor disorders, distinguishing different presentations of angina due to vasospasm and/or abnormal microvascular vasodilatation, developing invasive/non-invasive testing and treatment protocols, integrating diagnostic protocols into cardiologists' workflow and trials to inform guideline development were identified as key knowledge gaps and will be briefly addressed in this Viewpoint article. Setting: Virtual international meeting. Participants: Leading international experts in ischemic heart disease with no obstructive coronary artery disease. Interventions: None. Main outcome measures: None. Results: Topics discussed include: 1. Obstructive epicardial disease, functional vasospasm and microvascular disorders; 2. Under-recognition of coronary vasomotor disorders in clinical practice; 3. Complexity of coronary vasomotor disorders; 4. Understanding different presentations - vasospastic disease and microvascular angina; 5. Invasive/noninvasive testing and treatment protocols for vasospasm and microvascular angina assessment; 6. Treatment challenges; 7. Integrating diagnostic protocols into cardiologists' workflow; 8. The path forward to advance our approach to managing myocardial ischemia. Conclusions: Obstructive epicardial disease, functional vasospasm and microvascular disorders often co-exist and contribute to myocardial ischemia. Under-recognition, the complexity of coronary vasomotor disorders, understanding different presentations, testing and treatment protocols, treatment challenges, and integrating diagnostic protocols into cardiologists' workflow all contribute to the path forward to advance our management of myocardial ischemia for improved patient outcomes.
Published: 2021
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8. Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment for Post Infarct Angina in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries: A MINOCA-BAT Sub Study Rationale and Design

Author: Sivabaskari Pasupathy, Bertil Lindahl, Rosanna Tavella, Anna M. Nordenskjöld, Christopher Zeitz, Margaret Arstall, Matthew Worthley, Christopher Neil, Kuljit Singh, Stuart Turner, Adil Rajwani, John Mooney, and John F. Beltrame
Subjects: myocardial infarction, coronary angiogram, normal coronary angiography, non-obstructive coronary artery disease (NOCAD), Myocardial Infarction with Non Obstrucrive Coronary Arteries (MINOCA), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in ~10% of all patients with acute myocardial infarction (AMI), with an over-representation amongst women. Remarkably, it is estimated that as many as 1 in 4 patients with MINOCA experience ongoing angina at 12 months despite having no flow-restricting stenoses in their epicardial arteries. This manuscript presents the rationale behind Randomized Evaluation of Beta Blocker and Angiotensin-converting enzyme inhibitors/Angiotensin Receptor Blocker Treatment (ACEI/ARB) for Post Infarct Angina in MINOCA patients—The MINOCA BAT post infarct angina sub study.Methods: This trial is a registry-based, randomized, parallel, open-label, multicenter trial with 2 × 2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce post infarct angina in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 664 patients will be randomized into four groups; (i) ACEI/ARB with beta blocker, (ii) beta blocker only, (iii) ACEI/ARB only, or (iv) neither ACEI/ARB nor beta blocker and followed for 12 months.Results: The trial is currently recruiting in Australia and Sweden. Fifty six patients have been recruited thus far. Both sexes were equally distributed (52% women and 48% men) and the mean age was 56.3 ± 9.9 years.Conclusions: It remains unclear whether conventional secondary preventive therapies are beneficial to MINOCA patients in regard to post infarct angina. Existing registry-based literature suggest cardioprotective agents are less likely to be used in MINOCA patients. Thus, results from this trial will provide insights for future treatment strategies and guidelines specific to MINOCA patients.
Published: 2021
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9. Overcoming challenges of establishing a hospital-based out-of-hospital cardiac arrest registry: accuracy of case identification using administrative data and clinical registries

Author: Melanie R. Wittwer, Mohammed Ishaq Ruknuddeen, Mel Thorrowgood, Chris Zeitz, John F. Beltrame, and Margaret A. Arstall
Subjects: Out-of-hospital cardiac arrest, Registry, ICD-10, Administrative data, Utstein template, Validation, Specialties of internal medicine, RC581-951
Abstract: Introduction: Comprehensive identification of out-of-hospital cardiac arrest (OHCA) cases for inclusion in registries remains challenging due to the inherent diversity of OHCA aetiology, presentation, and management. The Northern Adelaide Local Health Network (NALHN) OHCA registry identifies OHCAs presenting to NALHN hospitals using existing data sources to monitor in-hospital treatment and survival. This study aimed to investigate the accuracy of hospital-based data sources for identifying OHCA cases treated at hospital. Methods: Retrospective analysis of all OHCAs aged >18 years included in the NALHN OHCA registry between 2011–16. Registry cases are identified from an emergency medical service (EMS) OHCA registry, Emergency Department (ED) and ICD-10 coding datasets, and key-word searches of two in-hospital clinical registries. Sensitivity and positive predictive values (PPV) of each hospital-based data source were analysed with respect to (a) the number of cases expected to be identified by that source, (b) total OHCA. Non-OHCAs yielded by each source were explored and a sub-analysis of ICD-10 codes was performed. Results: Between 2011–16, the four hospital-based sources yielded 992 cases, of which 383 were confirmed as OHCA. The ED coding dataset was the most accurate with a sensitivity and PPV of 78%. The ICD-10 coding dataset had good sensitivity but low PPV (33%). The ED coding dataset, combined with the two in-hospital clinical registries, identified 93% of OHCAs. Conclusions: No single dataset identified all OHCAs presenting to NALHN hospitals. Combined hospital-based data sources provide a valid method of identifying OHCAs treated at hospital that may be adapted to augment EMS-based data.
Published: 2021
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10. International prospective cohort study of microvascular angina – Rationale and design

Author: Akira Suda, Jun Takahashi, John F. Beltrame, Colin Berry, Paolo G. Camici, Filippo Crea, Javier Escaned, Tom Ford, Juan Carlos Kaski, Takahiko Kiyooka, Puja K. Metha, Peter Ong, Yukio Ozaki, Carl Pepine, Ornella Rimoldi, Basmah Safdar, Udo Sechtem, Kenichi Tsujita, Eric Yii, C. Noel Bairey Merz, and Hiroaki Shimokawa
Subjects: Coronary microvascular dysfunction, Microvascular angina, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery disease (CAD) frequently have coronary functional abnormalities, including coronary microvascular dysfunction. Those with the latter are grouped under the term “microvascular angina” (MVA). Although diagnostic criteria exist for MVA, as recently proposed by our COVADIS (COronary VAsomotor Disorders International Study) group and the condition has been increasingly recognized in clinical practice, the clinical characteristics and long-term prognosis of MVA patients in the current era remain to be fully elucidated. Aims: In the present study, we aimed to prospectively assess the clinical characteristics and long-term prognosis of MVA subjects in the current era in an international, multicenter, observational, and prospective registry study. Methods: A total of 15 medical centers across 7 countries (USA, UK, Germany, Spain, Italy, Australia, and Japan) enrolled subjects fulfilling the COVADIS diagnostic criteria for MVA as follows; (1) signs and/or symptoms of myocardial ischemia, (2) absence of obstructive CAD, and (3) objective evidence of myocardial ischemia and/or coronary microvascular dysfunction. The primary endpoint was the composite of major cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to heart failure or unstable angina. Between July 2015 and December 2018, a total of 706 subjects with MVA (M/F 256/450, 61.1 ± 11.8 [SD] yrs.) were registered. Subjects will be followed for at least 1 year. Summary: The present study will provide important information regarding the clinical characteristics, management, and long-term prognosis of MVA patients in the current era.
Published: 2020
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11. Identifying the Internalizing Disorder Clusters Among Recently Hospitalized Cardiovascular Disease Patients: A Receiver Operating Characteristics Study

Author: Megan Grech, Deborah A. Turnbull, Gary A. Wittert, Phillip J. Tully, the CHAMPS Investigators, John D. Horowitz, John F. Beltrame, Alison Barrett, Nathan Harrison, Christopher Bean, Terina Selkow, Libby Markwick, Bernhard T. Baune, Harald Baumeister, and Shannon Sauer-Zavala
Subjects: depression, anxiety, internalizing disorders, receiver operating characteristics, cardiovascular disease, post-traumatic stress disorder, Psychology, BF1-990
Abstract: Depression and anxiety disorders are common among cardiovascular disease (CVD) populations, leading several cardiology societies to recommend routine screening to streamline psychological interventions. However, it remains poorly understood whether routine screening in CVD populations identifies the broader groups of disorders that cluster together within individuals, known as anxious-misery and fear. This study examines the screening utility of four anxiety and depression questionnaires to identify the two internalizing disorder clusters; anxious-misery and fear. Patients with a recent hospital admission for CVD (n = 85, 69.4% males) underwent a structured clinical interview with the MINI International Neuropsychiatric Interview. The participants also completed the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7) scale, Overall Anxiety Severity Impairment Scale (OASIS), and the stress subscale of the Depression Anxiety Stress Scale (DASS). The PHQ-9 and the GAD-7 yielded appropriate screening properties to detect three different iterations of the anxious-misery cluster (sensitivity >80.95% and specificity >82.81%). The GAD-7 was the only instrument to display favorable screening properties to detect a fear cluster omitting post-traumatic stress disorder (PTSD) but including obsessive-compulsive disorder (OCD; sensitivity 81.25%, specificity 76.81%). These findings indicate that the PHQ-9 and GAD-7 could be implemented to reliably screen for anxious-misery disorders among CVD in-patients, however, the receiver operating characteristics (ROC) to detect fear disorders were contingent on the placement of PTSD and OCD within clusters. The findings are discussed in relation to routine screening guidelines in CVD populations and contemporary understandings of the internalizing disorders.
Published: 2019
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12. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study

Author: Basmah Safdar, Erica S. Spatz, Rachel P. Dreyer, John F. Beltrame, Judith H. Lichtman, John A. Spertus, Harmony R. Reynolds, Mary Geda, Héctor Bueno, James D. Dziura, Harlan M. Krumholz, and Gail D'Onofrio
Subjects: acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries, nonobstructive, prognosis, sex, women, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background We compared the clinical characteristics and outcomes of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) versus obstructive disease (myocardial infarction due to coronary artery disease [MI‐CAD]) and among patients with MINOCA by sex and subtype. Methods and Results Between 2008 and 2012, VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) prospectively enrolled acute myocardial infarction patients aged 18 to 55 years in 103 hospitals at a 2:1 ratio of women to men. Using an angiographically driven taxonomy, we defined patients as having MI‐CAD if there was revascularization or plaque ≥50% and as having MINOCA if there was
Published: 2018
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13. Mechanisms Responsible for Serotonin Vascular Reactivity Sex Differences in the Internal Mammary Artery

Author: Victor Lamin, Amenah Jaghoori, Rachel Jakobczak, Irene Stafford, Tamila Heresztyn, Michael Worthington, James Edwards, Fabiano Viana, Robert Stuklis, David P. Wilson, and John F. Beltrame
Subjects: hypersensitivity, internal mammary artery, serotonin, thromboxane A2, vascular biology, vascular endothelium, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (IMA) to endogenous vasoconstrictors in women, resulting in a predilection to myocardial ischemia. This study evaluated sex differences in serotonin and thromboxane A2 dependent vasoconstriction in human isolated IMA, with the mechanistic role of (1) the endothelium, (2) nitric oxide (NO), (3) prostaglandins, and (4) receptor activity investigated for any observed sex difference. Methods and Results Viable isolated human IMA segments were obtained from 116 patients (44 women [mean age, 66.8±12.2 years] and 72 men [mean age, 66.6±10.4 years]) undergoing coronary artery bypass grafting. Cumulative concentration‐response curves for serotonin and thromboxane A2 mimetic, U46619, were determined and revealed an increased sensitivity to serotonin but not U46619 in women. This sex difference to serotonin was further assessed by the following: (1) endothelial denudation, (2) endothelial NO synthase inhibition and NO quantification using electron paramagnetic resonance, (3) cyclooxygenase inhibition and prostaglandin metabolite quantification using mass spectrometry, and (4) quantification of receptor activity status. The female hyperreactivity to serotonin was (1) abolished by endothelial denudation; (2) unaffected by NO synthase inhibition, with no difference in electron paramagnetic resonance–assessed NO levels; (3) abolished by cyclooxygenase inhibition (quantification of prostaglandins in IMA revealed a trend towards reduced 6‐keto prostaglandin F1α in female IMA; P=0.08); and (4) unrelated to receptor activity. Conclusions These data indicate that female IMAs are hyperreactive to serotonin but not U46619, with the former attributable to an endothelium‐dependent cyclooxygenase pathway.
Published: 2018
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14. Risk of Thrombosis in Patients Presenting with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA)

Author: Sivabaskari Pasupathy, Susan Rodgers, Rosanna Tavella, Simon McRae, and John F. Beltrame
Subjects: minoca, thrombophilia, coagulation factors, thrombosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Patients presenting with myocardial infarction (MI) in the absence of obstructive coronary artery disease (CAD) is termed MI with nonobstructive coronary arteries (MINOCA). The underlying pathophysiology of MINOCA is multifactorial and in situ formation and subsequent spontaneous lysis of a coronary thrombus is often hypothesized as one of the mechanisms. The objective of this study is to determine whether MINOCA patients had a greater prothrombotic tendency in comparison to MI patients with obstructive CAD (MICAD). Prospectively, blood samples of 25 consecutive MINOCA patients (58 (interquartile range [IQR]: 48, 75) years, 48% women) and 25 age-/gender-matched MICAD patients (58 (IQR: 50, 66) years, 48% women) were obtained at 1 month after the initial presentation and overall thrombin generation potential and congenital/acquired thrombophilia states were assessed. As regard to results, overall thrombin generation parameters were similar (p > 0.05) between the MINOCA and MICAD groups, highlighting similar endogenous thrombin potential (1,590 nM/min; IQR: 1,380, 2,000 vs. 1,750 nM/min; IQR: 1,500, 2,040, respectively). There were no significant differences between MINOCA and MICAD, respectively, in respect to the numbers of patients with congenital thrombophilia states including factor V Leiden (0 vs. 4%) and prothrombin gene mutation (8 vs. 4%), decreased antithrombin (8 vs. 0%), protein C (0 vs. 0%), and protein S (4 vs. 0%). None of the patients demonstrated presence of lupus anticoagulant and anticardiolipin antibodies. Although MINOCA patients revealed thrombotic characteristics that are similar to those with MICAD, the results from this study are inconclusive and a larger study with healthy control subjects is required to assess the risk of thrombosis in MINOCA.
Published: 2018
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15. Regional differences in percutaneous coronary intervention outcomes in STEMI patients with diabetes: The Asia-Pacific evaluation of cardiovascular therapies (ASPECT) collaboration

Author: Mark Y.Z. Wong, Jonathan J.L. Yap, Hui Jun Chih, Bryan P.Y. Yan, Alan Y.Y. Fong, John F. Beltrame, Ika Prasetya Wijaya, Hoai T.T. Nguyen, Angela L. Brennan, Christopher M. Reid, and Khung Keong Yeo
Subjects: Percutaneous Coronary Intervention, Treatment Outcome, Risk Factors, Diabetes Mellitus, Humans, ST Elevation Myocardial Infarction, Hong Kong, Middle Aged, Cardiology and Cardiovascular Medicine
Abstract: Diabetes is associated with poorer outcomes and increased complication rates in STEMI patients undergoing percutaneous coronary intervention (PCI). Data are notably lacking in the Asia-Pacific region. We report the overall association of Diabetes with clinical characteristics and outcomes in STEMI patients undergoing PCI across the Asia-Pacific, with a particular focus on regional differences.The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration consists of data from various PCI registries across Australia, Hong Kong, Singapore, Malaysia, Indonesia and Vietnam. Clinical characteristics, lesion characteristics, and outcomes were provided for STEMI patients. Key outcomes included 30-day overall mortality and major adverse cardiovascular events (MACE).A total of 12,144 STEMI patients (mean(SD) age 59.3(12.3)) were included, of which 3912 (32.2%) had diabetes. Patients with diabetes were likely to have a higher baseline risk profile, poorer clinical presentation, and more complex lesion patterns (all p 0.05). Across all regions, patients with diabetes had a higher rate of 30-day mortality and MACE (all p 0.05). After multivariable adjustment, diabetes was significantly associated with both increased 30-day mortality (9.6%vs 5.5%, OR 1.79 [95% CI 1.40-2.30]) and MACE (13.3% vs 8.6%, R 1.73 [1.44-2.08]). The association between diabetes and 30-day MACE varied by region (pDiabetes portends poorer clinical outcomes in STEMI patients undergoing PCI in the Asia-Pacific with regional variations noted. The development of effective preventative measures and interventional strategies targetted at this high-risk group is crucial.
Published: 2023
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16. Comprehensive Diagnostic Assessment in MINOCA

Author: John F. Beltrame
Subjects: Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine
Published: 2023
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17. Non‐Obstructive Coronary Artery Disease (MINOCA/INOCA)

Author: Angela M. Kucia and John F. Beltrame
Published: 2022
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18. Prevalence and real-world management of NSTEMI with multivessel disease

Author: Angus A W, Baumann, Rosanna, Tavella, Tracy M, Air, Aashka, Mishra, Nicholas J, Montarello, Margaret, Arstall, Chris, Zeitz, Matthew I, Worthley, John F, Beltrame, and Peter J, Psaltis
Subjects: cardiovascular system, Original Article, cardiovascular diseases, Cardiology and Cardiovascular Medicine, digestive system diseases
Abstract: BACKGROUND: Non-ST elevation myocardial infarction (NSTEMI) has higher post-discharge mortality than ST-elevation myocardial infarction (STEMI). Prognosis worsens in those with multivessel coronary disease (MVD). However, information about the prevalence and extent of MVD in NSTEMI is limited, in turn limiting insights into optimal treatment strategies. This study aimed to define the prevalence and extent of MVD, preferred treatment strategies and the predictors of MVD in a real-world NSTEMI population. METHODS: The Coronary Angiogram Database of South Australia (CADOSA) was used to identify consecutive patients presenting to major teaching hospitals with NSTEMI between 2012 and 2016. Obtaining clinical and angiographic details, patients were stratified by the number of significantly diseased vessels (0,1,2,3-VD), defined by a stenosis of ≥70%, or ≥50% in the left main coronary artery. Data was analysed retrospectively. RESULTS: The prevalence of MVD (2- or 3-VD) was 42% amongst 3,722 NSTEMI presentations. Multivariate logistic regression modelling showed age, male gender, diabetes, dyslipidaemia and prior myocardial infarction predicted MVD over 1-VD or 0-VD. Percutaneous coronary intervention (PCI) was performed in 42% of patients with MVD. This comprised 61% of 2-VD patients and only 22% of 3-VD patients, with 24% and 66% of each group referred for coronary bypass grafting, respectively. Among MVD patients treated with PCI, 76% had their culprit lesion treated alone in the index admission. CONCLUSIONS: In this NSTEMI cohort, over 40% had MVD. Notably, a minority of patients with MVD undergoing PCI received multivessel revascularisation. This real-world practice emphasises that further evaluation is required to determine whether complete revascularisation is beneficial in NSTEMI, as reported for STEMI.
Published: 2022
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19. Role of cardiac magnetic resonance imaging and troponin-T in definitive diagnosis of Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA)

Author: Christopher Yu, Silvan Meier, Dina Bestrawos, David Sun, Joseph Trieu, Andy SC. Yong, Christopher CY. Wong, John Yiannikas, Leonard Kritharides, John F. Beltrame, and Christopher Naoum
Subjects: Cardiology and Cardiovascular Medicine
Published: 2023
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20. Lost in translation: The impact of language barriers on the outcomes of patients receiving coronary artery revascularization

Author: Aashray K. Gupta, Oliver Kleinig, Sheryn Tan, Bhupesh Nagarathinam, Joshua G. Kovoor, Stephen Bacchi, Ammar Zaka, Cheng He, Andrie Stroebel, John F. Beltrame, Michael P. Vallely, Jayme S. Bennetts, and Guy J. Maddern
Subjects: General Medicine, Cardiology and Cardiovascular Medicine
Published: 2023
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21. Sex differences in treatment and outcomes amongst myocardial infarction patients presenting with and without obstructive coronary arteries: a prospective multicentre study

Author: Michael Lawless, Yolande Appelman, John F Beltrame, Eliano P Navarese, Hanna Ratcovich, Chris Wilkinson, Vijay Kunadian, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Microcirculation
Abstract: Aims Women have an increased prevalence of myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). Whether sex differences exist in the outcomes of patients with MI and obstructive coronary arteries (MIOCA) vs. MINOCA remains unclear. We describe sex-based differences in diagnosis, treatment, and clinical outcomes of patients with MINOCA vs. MIOCA. Methods and results A large-scale cohort study of patients with ST/non-ST elevation MI undergoing coronary angiography (01/2015–12/2019). Patient demographics, diagnosis, prescribed discharge medications, in-hospital complications, and follow-up data were prospectively collected. A total of 13 202 participants were included (males 68.2% and females 31.8%). 10.9% were diagnosed with MINOCA. Median follow-up was 4.62 years. Females (44.8%) were as commonly diagnosed with MINOCA as males (55.2%), unlike the male preponderance in MIOCA (male, 69.8%; female, 30.2%). Less secondary prevention medications were prescribed at discharge for MINOCA than MIOCA. There was no difference in mortality risk between MINOCA and MIOCA [in-hospital: adjusted odds ratio (OR) 1.32, 95% confidence interval (CI) 0.74–2.35, P = 0.350; long term: adjusted hazard ratio (HR) 1.03, 95% CI 0.81–1.31, P = 0.813]. MINOCA patients had reduced mortality at long-term follow-up if prescribed secondary prevention medications (aHR 0.64, 95% CI 0.47–0.87, P = 0.004). Females diagnosed with MIOCA had greater odds of in-hospital and 1-year mortality than males (aOR 1.50, 95% CI 1.09–2.07, P = 0.014; aHR 1.18, 95% CI 1.01–1.38, P = 0.048). Conclusion MINOCA patients have similar mortality rates as MIOCA patients. MINOCA patients were less likely than those with MIOCA to be discharged with guideline-recommended secondary prevention therapy; however, those with MINOCA who received secondary prevention survived longer. Females with MIOCA experienced higher mortality rates vs. males.
Published: 2023
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22. European Society of Cardiology: cardiovascular disease statistics 2021: Executive Summary

Author: Adam Timmis, Panos Vardas, Nick Townsend, Aleksandra Torbica, Hugo Katus, Delphine De Smedt, Chris P Gale, Aldo P Maggioni, Steffen E Petersen, Radu Huculeci, Dzianis Kazakiewicz, Victor de Benito Rubio, Barbara Ignatiuk, Zahra Raisi-Estabragh, Agnieszka Pawlak, Efstratios Karagiannidis, Roderick Treskes, Dan Gaita, John F Beltrame, Alex McConnachie, Isabel Bardinet, Ian Graham, Marcus Flather, Perry Elliott, Elias A Mossialos, Franz Weidinger, and Stephan Achenbach
Subjects: Adult, Europe, Male, Cardiovascular Diseases, Risk Factors, Health Policy, Cardiology, Income, Humans, Female, Cardiology and Cardiovascular Medicine
Abstract: Aims This report from the European Society of Cardiology (ESC) Atlas Project updates and expands upon the widely cited 2019 report in presenting cardiovascular disease (CVD) statistics for the 57 ESC member countries. Methods and results Statistics pertaining to 2019, or the latest available year, are presented. Data sources include the World Health Organization, the Institute for Health Metrics and Evaluation, the World Bank, and novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery. New material in this report includes sociodemographic and environmental determinants of CVD, rheumatic heart disease, out-of-hospital cardiac arrest, leftsided valvular heart disease, the advocacy potential of these CVD statistics, and progress towards World Health Organization (WHO) 2025 targets for non-communicable diseases. Salient observations in this report: (i) Females born in ESC member countries in 2018 are expected to live 80.8 years and males 74.8 years. Life expectancy is longer in high income (81.6 years) compared with middle-income (74.2 years) countries. (ii) In 2018, high-income countries spent, on average, four times more on healthcare than middle-income countries. (iii) The median PM2.5 concentrations in 2019 were over twice as high in middle-income ESC member countries compared with high-income countries and exceeded the EU air quality standard in 14 countries, all middle-income. (iv) In 2016, more than one in five adults across the ESC member countries were obese with similar prevalence in high and low-income countries. The prevalence of obesity has more than doubled over the past 35 years. (v) The burden of CVD falls hardest on middle-income ESC member countries where estimated incidence rates are ∼30% higher compared with high-income countries. This is reflected in disability-adjusted life years due to CVD which are nearly four times as high in middle-income compared with high-income countries. (vi) The incidence of calcific aortic valve disease has increased seven-fold during the last 30 years, with age-standardized rates four times as high in high-income compared with middle-income countries. (vii) Although the total number of CVD deaths across all countries far exceeds the number of cancer deaths for both sexes, there are 15 ESC member countries in which cancer accounts for more deaths than CVD in males and five-member countries in which cancer accounts for more deaths than CVD in females. (viii) The under-resourced status of middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, ablation procedures, device implantation, and cardiac surgical procedures. Conclusion Risk factors and unhealthy behaviours are potentially reversible, and this provides a huge opportunity to address the health inequalities across ESC member countries that are highlighted in this report. It seems clear, however, that efforts to seize this opportunity are falling short and present evidence suggests that most of the WHO NCD targets for 2025 are unlikely to be met across ESC member countries.
Published: 2022
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23. Management of vasospastic angina

Author: John F Beltrame
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Vasospastic angina is a well-established cause of chest pain that is caused by coronary artery spasm. It can be clinically diagnosed during a spontaneous episode by documenting nitrate-responsive rest angina with associated transient ischaemic ECG changes but more often requires provocative coronary spasm testing with acetylcholine during coronary angiography. Vasospastic angina may result in recurrent episodes of angina (including nocturnal angina), which can progress on to major adverse cardiac events. Calcium channel blockers are first-line therapy for this condition, given their anti-anginal and cardioprotective benefits. Despite an established diagnostic and therapeutic management pathway for vasospastic angina, this diagnosis is often overlooked in patients presenting with chest pain. Thus, there is need for increased clinical awareness of vasospastic angina to improve outcomes in affected patients.
Published: 2022

24. 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, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira 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Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, 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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
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25. The evolving role of cardiac imaging in patients with myocardial infarction and non-obstructive coronary arteries

Author: Ik-Kyung Jang, John F. Beltrame, Giampaolo Niccoli, Maria Chiara Meucci, Rosa Sicari, Rocco A. Montone, Filippo Crea, Michael Bode, Nicola Gaibazzi, and Chiara Bucciarelli-Ducci
Subjects: medicine.medical_specialty, Cardiac magnetic resonance, Computed Tomography Angiography, Context (language use), Coronary Angiography, Diagnostic tools, Predictive Value of Tests, medicine, Humans, In patient, Myocardial infarction, Intensive care medicine, Ultrasonography, Interventional, Cardiac imaging, MINOCA, Optical coherence tomography, business.industry, Precision medicine, Prognosis, medicine.disease, Coronary Vessels, Magnetic Resonance Imaging, Coronary arteries, Cardiac Imaging Techniques, medicine.anatomical_structure, Echocardiography, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Cardiology and Cardiovascular Medicine, business, Tomography, Optical Coherence
Abstract: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%–8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.
Published: 2021
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26. Histological regional analysis of the aortic root and thoracic ascending aorta: a complete analysis of aneurysms from root to arch

Author: Michael Worthington, Jim Manavis, John F. Beltrame, T. Surman, John W. Finnie, John M. Abrahams, Karen J. Reynolds, Dermot O'Rourke, and James Edwards
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Histology, RD1-811, Aorta, Thoracic, Aneurysm, Fibrosis, Anesthesiology, medicine.artery, Ascending aorta, medicine, Humans, Aortic root, RD78.3-87.3, cardiovascular diseases, Aorta, Aortic Aneurysm, Thoracic, biology, business.industry, General Medicine, medicine.disease, Immunohistochemistry, Pathophysiology, Aortic Aneurysm, Elastin, Cardiac surgery, Cardiothoracic surgery, biology.protein, cardiovascular system, Surgery, Cardiology and Cardiovascular Medicine, business, Aneurysms, Research Article
Abstract: Background Although aortic root and ascending aortic aneurysms are treated the same, they differ in embryological development and pathological processes. This study examines the microscopic structural differences between aortic root and ascending aortic aneurysms, correlating these features to the macroscopic pathophysiological processes. Methods We obtained surgical samples from ascending aortic aneurysms (n = 11), aortic root aneurysms (n = 3), and non-aneurysmal patients (n = 7), Aortic collagen and elastin content were examined via histological analysis, and immunohistochemistry techniques used to determine collagen I, III, and IV subtypes. Analysis was via observational features, and colour deconvolution quantification techniques. Results Elastin fiber disruption and fragmentation was the most extensive in the proximal aneurysmal regions. Medial fibrosis and collagen density increased in proximal aneurysmal regions and aortic root aneurysms (p Conclusions The aortic root differs histologically from the ascending aorta confirming its unique composition in aneurysm pathology. These findings should prompt further evaluation on the influence of this altered structure on function which could potentially guide clinical management.
Published: 2021

27. Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group

Author: John F. Beltrame, Juan Carlos Kaski, C. Noel Bairey Merz, Akira Suda, Paolo G. Camici, Ornella Rimoldi, Yukio Ozaki, Filippo Crea, Thomas J. Ford, Javier Escaned, Jun Takahashi, Peter Ong, Puja K. Mehta, Satoshi Yasuda, Carl J. Pepine, Udo Sechtem, Takahiko Kiyooka, Colin Berry, Hiroaki Shimokawa, Kenichi Tsujita, Eric Yii, and Basmah Safdar
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Coronary artery disease, Angina, 03 medical and health sciences, Microvascular angina, 0302 clinical medicine, Clinical Research, Risk Factors, Internal medicine, medicine, Clinical endpoint, Coronary microvascular dysfunction, Humans, AcademicSubjects/MED00200, Prospective Studies, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Prospective cohort study, Unstable angina, business.industry, Epidemiology and Prevention, Prognosis, medicine.disease, Editor's Choice, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Quality of Life, Female, Cardiology and Cardiovascular Medicine, business, Mace
Abstract: Aims To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). Methods and results The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365–744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). Conclusions This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis., Graphical Abstract
Published: 2021
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28. Applying a framework to assess the impact of cardiovascular outcomes improvement research

Author: David Brieger, Suzanne Robinson, Danny Liew, Mark Nelson, Louise Cullen, Peter S. Macdonald, Derek P. Chew, Stephen J. Duffy, John F. Beltrame, Tom Briffa, Christopher A. Reid, Julian A. Smith, and Mitchell Sarkies
Subjects: Cardiovascular outcomes, Biomedical Research, Research impact, National Health Programs, Cost-Benefit Analysis, Dissemination, 030204 cardiovascular system & hematology, Medicare, Research output, Health research, Knowledge translation, Health administration, 03 medical and health sciences, 0302 clinical medicine, 1117 Public Health and Health Services, 1605 Policy and Administration, Humans, 030212 general & internal medicine, Economic impact analysis, Evaluation, Health policy, Reimbursement, Aged, Medical education, Impact factor, Research translation, Health Policy, Research, Health services research, Australia, Impact matrix, Medical research, United States, Health Policy & Services, Implementation science, Journal Impact Factor, Public aspects of medicine, RA1-1270, Psychology
Abstract: Background Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016–2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research. Methods We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients. Results By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery. Conclusions We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.
Published: 2021

29. Shortcomings in Managing Patients With Ischemia With Nonobstructed Coronary Arteries

Author: Rosanna Tavella and John F. Beltrame
Subjects: Ischemia, Coronary Circulation, Humans, Coronary Angiography, Cardiology and Cardiovascular Medicine, Coronary Vessels, Angina Pectoris
Published: 2022
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30. Refining the Role of CMR Imaging in MINOCA

Author: Sivabaskari Pasupathy and John F. Beltrame
Subjects: medicine.medical_specialty, Takotsubo syndrome, Myocarditis, business.industry, medicine.disease, Refining, Internal medicine, medicine, Cardiology, Radiology, Nuclear Medicine and imaging, Myocardial infarction, Cardiology and Cardiovascular Medicine, Cardiac magnetic resonance, business
Published: 2021
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31. Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design

Author: Chris P Gale, John F. Beltrame, Tomas Jernberg, Harmony R. Reynolds, Bertil Lindahl, Per Tornvall, Annica Ravn-Fisher, Tomasz Baron, J. Somaratne, Javier López-Pais, Olle Bergström, David Erlinge, Dan Atar, Pelle Johansson, Stefan Agewall, and Anna M. Nordenskjöld
Subjects: Male, medicine.medical_specialty, Angiotensin receptor, medicine.drug_class, Adrenergic beta-Antagonists, Myocardial Infarction, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Patient Readmission, Ventricular Function, Left, law.invention, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Cause of Death, Multicenter trial, Internal medicine, Atrial Fibrillation, Secondary Prevention, medicine, Humans, Cardiac and Cardiovascular Systems, Angina, Unstable, Prospective Studies, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Beta blocker, Ischemic Stroke, Heart Failure, Sweden, Kardiologi, Ejection fraction, business.industry, Australia, Stroke Volume, Middle Aged, medicine.disease, Coronary Vessels, Sample Size, Heart failure, ACE inhibitor, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6–8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial ‘Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients’ (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. Methods MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. Summary While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.
Published: 2021
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32. Cardiologists appropriately exclude resuscitated out‐of‐hospital cardiac arrests from emergency coronary angiography

Author: Melanie R. Wittwer, Sunny Wu, Margaret Arstall, John F. Beltrame, Kumaril Mishra, Christopher Zeitz, and Sharmalar Rajendran
Subjects: Out of hospital, Coronary angiography, medicine.medical_specialty, business.industry, medicine.medical_treatment, Clinical judgement, percutaneous coronary intervention, education, Cardiology, Statistical difference, Percutaneous coronary intervention, Working diagnosis, Revascularization, out‐of‐hospital cardiac arrest, Emergency medicine, medicine, cardiovascular diseases, coronary angiography, business, Prospective cohort study, Original Research
Abstract: Objective Emergency coronary angiography after resuscitated out‐of‐hospital cardiac arrest as a selective or non‐selective diagnostic procedure with or without intervention continues to be the subject of debate. This study sought to determine if cardiologists reliably select patients using clinical judgement for emergency coronary angiography without missing acutely ischemic cases requiring revascularization. Methods Presenting clinical details and ECGs (within 2 hours) from 52 consecutive out‐of‐hospital cardiac arrest patients who underwent non‐selective coronary angiography were compiled retrospectively. Three out‐of‐hospital cardiac arrest‐experienced interventional cardiologists, blinded to patient outcome, independently determined working diagnosis, and decision for emergency coronary angiography using clinical judgement. Sensitivity of the cardiologists’ decision was assessed with respect to the outcome of acute revascularization. Inter‐rater differences, consensus in clinical assessment, and influence of working diagnosis were also investigated. Results Sensitivity of individual cardiologist's decision for emergency coronary angiography with respect to acute revascularization was very high (adjusted overall sensitivity = 95.8%, 95% CI = 89–100, cardiologist range = 93%–100%), and perfect for the consensus of 2 or more cardiologists (100%, 95% CI = 79.4–100). There was no statistical difference in the sensitivity of this decision between cardiologists (P
Published: 2020
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33. Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells

Author: Peter D. Zalewski, A. Abdo, Sandra Hodge, Hai Bac Tran, and John F. Beltrame
Subjects: 0303 health sciences, Chemistry, Endocrinology, Diabetes and Metabolism, 030302 biochemistry & molecular biology, Biochemistry (medical), Clinical Biochemistry, Cell, chemistry.chemical_element, Transporter, General Medicine, Zinc, 010501 environmental sciences, 01 natural sciences, Biochemistry, Cell biology, Inorganic Chemistry, Endothelial stem cell, 03 medical and health sciences, medicine.anatomical_structure, Gene expression, medicine, Metallothionein, Homeostasis, Intracellular, 0105 earth and related environmental sciences
Abstract: Zinc is an important essential micronutrient with anti-oxidative and anti-inflammatory properties in humans. The role of zinc in signalling has been characterized in the nervous, endocrine, gastrointestinal, renal and reproductive systems. Relatively little is known regarding its role in the vascular system, but the role of zinc homeostasis in augmenting vascular health and vasorelaxation is emerging. Zinc transport proteins are integral to the protective function of zinc, but knowledge of their expression in vascular endothelial and smooth muscle cells is lacking. Human coronary artery endothelial cells and pulmonary artery smooth muscle cells were assessed for gene expression (RT-PCR) of SLC39A (ZIP), SLC30A (ZnT) and metallothionein (MT) families of Zn transporters and storage proteins. Protein expression (fluorescence confocal microscopy) was then analysed for the proteins of interest that changed mRNA expression: ZIP2, ZIP12, ZnT1, ZnT2 and MT1/2. Endothelial and smooth muscle cell mRNA expression of ZnT1, ZnT2 and MT1 was significantly downregulated by low and high Zn conditions, while ZIP2 and ZIP12 expression was induced by Zn depletion with the Zn chelator, TPEN. Changes in gene expression were consistent with protein expression levels for ZIP2, ZIP12 and MT1, where ZIP2 was localized to intracellular bodies and ZIP12 to lamellipodia. Vascular endothelial and smooth muscle cells actively regulate specific Zn transport and metallothionein gene and protein expressions to achieve Zn homeostasis.
Published: 2020
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34. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease

Author: Thomas J. Ford, Colin Berry, Peter Ong, Paolo G. Camici, Carl J. Pepine, C. Noel Bairey Merz, Filippo Crea, Udo Sechtem, John F. Beltrame, Juan Carlos Kaski, and Hiroaki Shimokawa
Subjects: Acute coronary syndrome, medicine.medical_specialty, Heart disease, Vascular disease, business.industry, Ischemia, Vasospasm, 030204 cardiovascular system & hematology, medicine.disease, Angina, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Heart catheterization, medicine, Cardiology, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.
Published: 2020
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35. The Association between Sleep Duration and Quality with Readmissions: An Exploratory Pilot-Study among Cardiology Inpatients

Author: Robert J. Adams, Tracy Air, John F. Beltrame, Clementine Labrosciano, Isuru Ranasinghe, Rosanna Tavella, and Amy C. Reynolds
Subjects: medicine.medical_specialty, lcsh:Medicine, Article, readmissions, Pittsburgh Sleep Quality Index, inpatients, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, 030212 general & internal medicine, General Environmental Science, Sleep disorder, business.industry, lcsh:R, Actigraphy, medicine.disease, Telephone interview, cardiology, Cohort, Cardiology, Coronary care unit, General Earth and Planetary Sciences, business, 030217 neurology & neurosurgery, Cohort study, actigraphy
Abstract: Background: Readmissions within 30 days of discharge are prominent among patients with cardiovascular disease. Post hospital syndrome hypothesizes that sleep disturbance during the index admission contributes to an acquired transient vulnerability, leading to increased risk of readmission. This study evaluated the association of in-hospital sleep (a) duration and (b) quality with 30-day all-cause unplanned readmission. Methods: This prospective observational cohort study included patients admitted to the coronary care unit of a South Australian hospital between 2016&ndash, 2018. Study participants were invited to wear an ActiGraph GT3X+ for the duration of their admission and for two weeks post-discharge. Validated sleep and quality of life questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), were administered. Readmission status and questionnaires were assessed at 30 days post-discharge via patient telephone interview and a review of hospital records. Results: The final cohort consisted of 75 patients (readmitted: n = 15, non-readmitted: n = 60), of which 72% were male with a mean age 66.9 &plusmn, 13.1 years. Total sleep time (TST), both in hospital (6.9 &plusmn, 1.3 vs. 6.8 &plusmn, 2.9 h, p = 0.96) and post-discharge (7.4 &plusmn, 1.3 h vs. 8.9 &plusmn, 12.6 h, p = 0.76), was similar in all patients. Patient&rsquo, s perception of sleep, reflected by PSQI scores, was poorer in readmitted patients (9.13 &plusmn, 3.6 vs. 6.4 &plusmn, 4.1, p = 0.02). Conclusions: Although an association between total sleep time and 30-day readmission was not found, patients who reported poorer sleep quality were more likely to be readmitted within 30 days. This study also highlighted the importance of improving sleep, both in and out of the hospital, to improve the outcomes of cardiology inpatients.
Published: 2020

36. The Impact of Cardiac Rehabilitation and Secondary Prevention Programs on 12-Month Clinical Outcomes: A Linked Data Analysis

Author: Carolyn Astley, Robyn Clark, Rosanna Tavella, Rosy Tirimacco, Derek P. Chew, Stephen J. Nicholls, John F. Beltrame, Matthew Horsfall, and Wendy Keech
Subjects: Male, Pulmonary and Respiratory Medicine, Clinical audit, medicine.medical_specialty, Databases, Factual, Heart Diseases, Referral, medicine.medical_treatment, 030204 cardiovascular system & hematology, Patient Readmission, 03 medical and health sciences, 0302 clinical medicine, Secondary Prevention, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Stroke, Aged, Retrospective Studies, Aged, 80 and over, Cardiac Rehabilitation, Rehabilitation, business.industry, Attendance, Retrospective cohort study, Middle Aged, medicine.disease, Emergency medicine, Female, Outcomes research, Cardiology and Cardiovascular Medicine, business
Abstract: Guidelines recommend referral to cardiac rehabilitation (CR) for cardiac event prevention and risk factor management, but poor attendance persists. Following the development of standardised data and uniform capture, CR services have contributed to three audits in South Australia, Australia. We aimed to determine if CR attendance impacts on cardiovascular readmission, morbidity and mortality.In a retrospective cohort study, CR databases were linked to hospital administrative datasets to compare the characteristics and outcomes of CR patients between 2013 and 2015. Inverse probability weighting methods were used to measure associations between CR attendance versus non-attendance and cardiovascular readmission and the composite of death, new/re-myocardial infarction, atrial fibrillation, heart failure and stroke within 12-months.Of 49,909 eligible separations, 15,089/49,909 (30.2%) were referred to CR with an attendance rate of 4,286/15,089 (28.4%). Referred/declined patients were older (median: 67.3 vs 65.3 years, p 0.001), more likely to be female (32.3% vs 26.5%, p 0.001) with more heart failure (17.1% vs 10.9%, p 0.001) and arrhythmia (6.1% vs 2.1%, p 0.001) admissions and higher socio-economic disadvantage (median Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD): 950.1 vs 960.4, p 0.001). Referred/attended patients had lower cardiovascular readmission, (referred/attended vs not referred: 15.6% vs 22.7% and referred/attended vs referred/declined: 15.6% vs 29.6%, p 0.001). After clinical and social factors adjustment there was no difference in composite outcomes, but attendance was associated with reduced cardiovascular readmission (HR:0.68, 95% IQR: 0.58-0.81, p = 0.001).Audit can measure service effectiveness, identifying areas for improvement. This study highlights patient eligibility, system and program considerations for future CR services.
Published: 2020
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37. International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients

Author: Gerasimos Filippatos, Victoria Parker, Sabrina Bernardez-Pereira, Jillian P. Riley, Jason Arora, Stephen Hutchison, Tina Kinsella, Theresa McDonagh, Carolyn S.P. Lam, Daniel J.P. Burns, Hans Persson, Hugh McIntyre, John F. Beltrame, Lynne W. Stevenson, Mariell Jessup, Richard Mindham, Oluwakemi Okunade, Marisa G. Crespo-Leiro, Luuk Otterspoor, Arno W. Hoes, Claude Pinnock, Louise Morgan, Michael Knapton, Christopher M. Reid, Suzanna M C Hardman, and Frederick A. Masoudi
Subjects: quality and outcomes, Standardization, media_common.quotation_subject, 030204 cardiovascular system & hematology, Health outcomes, Article, 03 medical and health sciences, 0302 clinical medicine, Patient-Centered Care, Surveys and Questionnaires, medicine, Humans, Quality (business), Patient Reported Outcome Measures, 030212 general & internal medicine, ICHOM, International Consortium for Health Outcomes Measurement, Set (psychology), Quality of Health Care, media_common, Heart Failure, KCCQ, Kansas City Cardiomyopathy Questionnaire, business.industry, Patient-centered outcomes, MLHFQ, Minnesota Living with Heart Failure Questionnaire, medicine.disease, PROM, patient-reported outcome measure, Heart failure, Quality of Life, epidemiology, Medical emergency, Cardiology and Cardiovascular Medicine, business
Abstract: Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group’s objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide., Central Illustration, Highlights • ICHOM seeks to help standardize and align outcome measurement efforts globally. • Standardization and alignment of this sort does not exist for heart failure. • The heart failure working group developed a standard set of 17 outcomes to be measured. • ICHOM hopes this standardization effort will increase quality and value in heart failure care.
Published: 2020
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38. Validation of contemporary electrocardiographic indices of area at risk and infarct size in acute ST elevation myocardial infarction (STEMI)

Author: Yang Timothy Du, Christopher Neil, Tracy Air, John F. Beltrame, and Sivabaskari Pasupathy
Subjects: Male, medicine.medical_specialty, Heart Ventricles, medicine.medical_treatment, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Coronary Angiography, Risk Assessment, Severity of Illness Index, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Prospective Studies, cardiovascular diseases, 030212 general & internal medicine, Artery occlusion, Myocardial infarction, Prospective cohort study, Survival rate, medicine.diagnostic_test, business.industry, Australia, Percutaneous coronary intervention, Magnetic resonance imaging, Middle Aged, medicine.disease, Survival Rate, cardiovascular system, Cardiology, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Electrocardiographic (ECG) methods to assess area at risk (AAR) and infarct size (IS) in patients with ST-elevation myocardial infarction (STEMI) have been previously established but not validated against contemporary benchmark Cardiac Magnetic Resonance (CMR) measures. We compared ECG-determined and CMR-determined measures for (a) AAR, (b) IS, and (c) myocardial salvage.Sixty patients with ECG evidence of STEMI and CMR imaging performed within 13 days were included. The ECG-determined (a) AAR scores (Aldrich and Wilkins), (b) IS (Selvester score), and (c) myocardial salvage (i.e. [AAR-IS] / AAR × 100%), were compared with CMR-determined measures.Compared with CMR-determined AAR, both the WilkinsAldrich scores underestimated AAR, although the Wilkins (r = 0.72, p 0.001) showed a better correlation than the Aldrich (r = 0.54, p 0.001). Bland-Altman analysis revealed a bias of 2.6% (95% limits of agreement: 18.5%, -13.3%) for the Wilkins and 5.9% (95% limits of agreement: 25.6%, -13.8%) for the Aldrich. Estimation of IS was similar between the Selvester score and CMR, with good correlation (r = 0.77, p 0.001) and agreement (fixed bias 0.4%, 95% limits of agreement 20.8%, -15.5%). However, ECG-determined myocardial salvage significantly underestimated CMR-determined myocardial salvage, with an inverse correlation (r = -0.33, p = 0.01).The Wilkins score is superior to Aldrich score as an ECG-AAR index, Selvester score is a reasonable ECG estimate of infarct size, though ECG derived myocardial salvage does not have enough accuracy to be used in the clinical setting; it may be an inexpensive surrogate for myocardial salvage in large research studies. Further validation and prognostic studies are required.
Published: 2020
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39. Beyond Structural Angiography: The Emergence of Functional Coronary Angiography

Author: John F, Beltrame, Rosanna, Tavella, and Christopher J, Zeitz
Subjects: Angina Pectoris, Variant, Coronary Vasospasm, Humans, Coronary Angiography, Coronary Vessels
Published: 2022

40. Impact of COVID-19 restrictions on pathology service utilisation

Author: Elizabeth E. Roughead, Marianne Gillam, Richard Ryan, John F. Beltrame, Peter D. O’Loughlin, Tom Dodd, Rosanna Tavella, Gillam, Marianne H, Roughead, Elizabeth, Tavella, Rosanna, Dodd, Tom, Beltrame, John, Ryan, Richard, and O'Loughlin, Peter
Subjects: Pathology, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Health outcomes, pathology services, COVID‐19, Health care, Internal Medicine, Medicine, Humans, Baseline (configuration management), Pandemics, Aged, Service (business), business.industry, SARS-CoV-2, troponin, Social distance, COVID-19, Original Articles, Cross-Sectional Studies, Baseline time, Communicable Disease Control, Pathology services, Community setting, Original Article, business
Abstract: Refereed/Peer-reviewed Background: Isolation and social distancing restrictions due to COVID-19 have the potential to impact access to healthcare services. Aims: To assess the use of pathology services during the COVID-19 pandemic initial restrictions. Methods: Repeated cross-sectional study of pathology tests utilisation during a baseline time period early in 2020 compared with pre-lockdown and lockdown due to COVID-19 in South Australia. The outcome measure was changed in a number of pathology tests compared to baseline period, particularly change in the number of troponin tests to determine potential impacts of lockdown on urgent care presentations. Results: In the community setting, the ratio of a number of pathology tests pre-lockdown and post-lockdown versus baseline period decreased from 1.02 to 0.53 respectively. The exception was microbiology molecular tests, where the number of tests was more than three times higher in the lockdown period. The number of troponin tests in emergency departments decreased in the lockdown period compared to the baseline time period; however, there was no evidence of an association between tests result (positive vs negative) and time period (odds ratio (OR) 1.09; 95% confidence interval (CI) 0.97–1.22). There was an inverse relationship between age and time period (OR 0.995; 95% CI 0.993–0.997), indicating that fewer troponin tests were conducted in older people during the lockdown compared with the baseline period. Conclusion: COVID-19 restrictions had a significant impact on the use of pathology testing in both urgent and non-urgent care settings. Further studies are needed to investigate the effect on health outcomes as a result of the COVID-19 restrictions.
Published: 2022

41. Clinico-pathophysiological considerations in coronary microvascular disorders

Author: Sarena La, Rosanna Tavella, Sivabaskari Pasupathy, and John F. Beltrame
Subjects: cardiovascular diseases, Cardiology and Cardiovascular Medicine
Abstract: Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.
Published: 2022
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42. Abstract 10737: The Impact of Diabetes on Percutaneous Coronary Intervention Outcomes in STEMI Patients: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) Collaboration

Author: Mark Y Wong, Jonathan J Yap, Hui Jun Chih, Angela L Brennan, Bryan P Yan, Alan Fong, John F Beltrame, Ika P Wijaya, Hoai Nguyen, Christopher Reid, and Khung Keong K Yeo
Subjects: Physiology (medical), cardiovascular diseases, Cardiology and Cardiovascular Medicine
Abstract: Introduction: Diabetes is associated with poorer outcomes and increased complication rates in STEMI patients undergoing percutaneous coronary intervention (PCI). Regional variations have been described but data are notably lacking in the Asia-Pacific region. Aims: We report the associations of diabetes with clinical characteristics and outcomes in STEMI patients undergoing PCI across the Asia-Pacific. Methods: The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration consists of data from the registries of contributing PCI centres across Australia, Hong Kong, Singapore, Malaysia, Indonesia and Vietnam. Clinical characteristics, lesion characteristics, and outcomes were provided for STEMI patients. Key outcomes included overall mortality at 30 days, and major adverse cardiovascular events (MACE; defined as peri-procedural myocardial infarctions, emergency CABG, stent thrombosis, target vessel revascularisation, cerebrovascular events, or death) at 30 days. Results: A total of 12,144 STEMI patients (mean(SD) age 59.3(12.3)) were included, of which 3912 (32.2%) had diabetes. Patients with diabetes were likely to be older, have a history of cardiovascular disease and previous acute coronary events (all p20mm (all p Conclusions: Diabetes portends poorer clinical outcomes in STEMI patients undergoing PCI in the Asia-Pacific. The development of effective preventative measures and interventional strategies targeted at this high-risk group is crucial.
Published: 2021
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43. The susceptibility of the aortic root: porcine aortic rupture testing under cardiopulmonary bypass

Author: Chris Christou, James Edwards, Michael Worthington, T. Surman, John F. Beltrame, John W. Finnie, Georgia Kate Williams, Jim Manavis, Angela Walls, Mark E. Adams, John M. Abrahams, and Peter Frantzis
Subjects: Pulmonary and Respiratory Medicine, Aortic valve, medicine.medical_specialty, Histology, RD1-811, Swine, Aortic aneurysms, Aortic Rupture, medicine.medical_treatment, law.invention, Anesthesiology, law, medicine.artery, Internal medicine, Ascending aorta, medicine, Cardiopulmonary bypass, Animals, Animal model, RD78.3-87.3, Aortic rupture, Aorta, Aortic Aneurysm, Thoracic, business.industry, Wall sheer stress, General Medicine, Cardiac surgery, medicine.anatomical_structure, Median sternotomy, Cardiothoracic surgery, Aortic Valve, cardiovascular system, Cardiology, Surgery, Cardiology and Cardiovascular Medicine, business, Research Article
Abstract: Background In our earlier study on the functional limits of the aneurysmal aortic root we determined the pig root is susceptible to failure at high aortic pressures levels. We established a pig rupture model using cardiopulmonary bypass to determine the most susceptible region of the aortic root under the highest pressures achievable using continuous flow, and what changes occur in these regions on a macroscopic and histological level. This information may help guide clinical management of aortic root and ascending aorta pathology. Methods Five pigs underwent 4D flow MRI imaging pre surgery to determine vasopressor induced wall sheer stress and flow parameters. All pigs were then placed on cardiopulmonary bypass (CPB) via median sternotomy, and maximal aortic root and ascending aorta flows were initiated until rupture or failure, to determine the most susceptible region of the aorta. The heart was explanted and analysed histologically to determine if histological changes mirror the macroscopic observations. Results The magnetic resonance imaging (MRI) aortic flow and wall sheer stress (WSS) increased significantly in all regions of the aorta, and the median maximal pressures obtained during cardiopulmonary bypass was 497 mmHg and median maximal flows was 3.96 L/m. The area of failure in all experiments was the non-coronary cusp of the aortic valve. Collagen and elastin composition (%) was greatest in the proximal regions of the aorta. Collagen I and III showed greatest content in the inner aortic root and ascending aorta regions. Conclusions This unique porcine model shows that the aortic root is most susceptible to failure at high continuous aortic pressures, supported histologically by different changes in collagen content and subtypes in the aortic root. With further analysis, this information could guide management of the aortic root in disease.
Published: 2021
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44. Clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina

Author: Akira Suda, Atsushi Hirayama, Tetsuya Sumiyoshi, Takahiko Kiyooka, Koichi Kaikita, John F. Beltrame, Juan Carlos Kaski, Katsuhisa Ishii, Shozo Sueda, Kazuo Kimura, Hiroaki Shimokawa, Filippo Crea, Koichi Sato, Paolo G. Camici, Jun Takahashi, Peter Ong, Udo Sechtem, Yuji Odaka, Hiroki Teragawa, and Yasuhiko Tanabe
Subjects: Vasospastic angina, medicine.medical_specialty, business.industry, Provocation test, Ethnic group, 030204 cardiovascular system & hematology, medicine.disease, Angina, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, 030212 general & internal medicine, Medical prescription, Cardiology and Cardiovascular Medicine, business, Survival rate, Mace, Morning
Abstract: Background Possible ethnic differences in clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina (VSA) remain to be elucidated. Methods and results The Japanese Coronary Spasm Association (JCSA) conducted an international, prospective, and multicenter registry study for VSA patients. A total of 1457 VSA patients (Japanese/Caucasians, 1339/118) were enrolled based on the same diagnostic criteria. Compared with Caucasian patients, Japanese patients were characterized by higher proportions of males (68 vs. 51%) and smoking history (60 vs. 49%). Japanese patients more often had angina especially during the night and early morning hours, compared with Caucasians. Ninety-five percent of Japanese and 84% of Caucasian patients underwent pharmacological provocation test. Importantly, no significant differences in the patterns of coronary spasm were apparent, with diffuse spasm most frequently noted in both ethnicities. The prescription rate of calcium-channel blockers was higher in Japanese (96 vs. 86%), whereas the uses of nitrates (46 vs. 59%), statins (43 vs. 65%), renin-angiotensin-system inhibitors (27 vs. 51%), and β-blockers (10 vs. 24%) were more common in Caucasian patients. Survival rate free from major adverse cardiac events (MACE) was slightly but significantly higher in Japanese than in Caucasians (86.7 vs. 76.6% at 5 years, P Conclusion These results indicate that there are ethnic differences in clinical profiles and long-term prognosis of contemporary VSA patients.
Published: 2019
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45. Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study

Author: James K. Min, Roxy Senior, Michel G. Khouri, Khaled Abdul-Nour, Yi Li, Michael H. Picard, Leonid Bershtein, Khaled Alfakih, Kian Keong Poh, Michael D. Shapiro, Mark de Belder, David J. Maron, Harmony R. Reynolds, Mohammad El-Hajjar, Judith S. Hochman, John A. Spertus, Jelena Celutkiene, Rebecca Anthopolos, John F. Beltrame, Jesús Peteiro, Patricia A. Pellikka, José Luis López Sendón, Dennis Kunichoff, and Jerome L. Fleg
Subjects: Male, medicine.medical_specialty, business.industry, Ischemia, Microvascular angina, Coronary Artery Disease, Middle Aged, medicine.disease, Natural history, Coronary artery disease, Physiology (medical), Internal medicine, medicine, Cardiology, Humans, Female, cardiovascular diseases, Cardiology and Cardiovascular Medicine, business, Aged, Natural History
Abstract: Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P P =0.46) or ISCHEMIA stress echocardiography participants ( P =0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). Conclusions: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02347215.
Published: 2021

46. Establishing Thresholds for Minimal Clinically Important Differences for the Peripheral Artery Disease Questionnaire

Author: Mehdi H. Shishehbor, Yuanyuan Tang, David L. Safley, Jingyan Wang, Kensey Gosch, Manesh R. Patel, Matthew C. Bunte, Kim G. Smolderen, Qurat-ul-ain Jelani, Carlos Mena-Hurtado, J. Dawn Abbott, Herbert D. Aronow, John A. Spertus, Clementine Labrosciano, Poghni A. Peri-Okonny, and John F. Beltrame
Subjects: medicine.medical_specialty, Arterial disease, business.industry, Minimal clinically important difference, Minimal Clinically Important Difference, Disease, Intermittent Claudication, Article, Peripheral Arterial Disease, Quality of life, Surveys and Questionnaires, medicine, Quality of Life, Humans, Female, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Aged
Abstract: Background: Understanding minimum clinically important differences (MCID) in patient-reported outcomes is essential in interpreting the magnitude of changes in these measures. No MCID from patients’ perspectives has ever been published for peripheral artery disease–specific health status assessment tools. The Peripheral Artery Questionnaire (PAQ) is a commonly used, validated peripheral artery disease–specific health status instrument for which we sought to prospectively establish its MCID from patients’ perspectives. Methods and Results: Patients presenting to vascular clinics with new or worsened claudication in the US cohort of the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry who completed baseline and follow-up PAQ assessments along with the Global Assessment of Functioning scale were included. Mean change in PAQ summary scores from 3- to 6-month follow-up was calculated according to Global Assessment of Functioning category. MCID was defined as the mean difference in scores between those with small improvement or deterioration and those with no change. Multivariable linear regression was used to provide an MCID estimate after adjusting for patients’ 3-month PAQ score. Of the 483 patients who completed the Global Assessment of Functioning score at 6 months and who had available 3- and 6-month PAQ assessments, the mean age was 69 years, 42% were female, and 71% were White. The MCIDs for PAQ summary scale improvement and worsening were 8.7 (2.9–14.5) and −11.0 (−18.6 to −3.3), respectively. After multivariable adjustment, these were 8.9 (3.0–14.8) and −11.2 (−18.2 to −4.2), respectively. There was no significant interaction between treatment (invasive versus noninvasive) and Global Assessment of Functioning response ( P =0.75). Conclusions: In patients with new or worsened claudication, a 10-point change in PAQ summary score represents an MCID. This estimate needs external validation and may inform the interpretation of PAQ scores when used as outcomes in clinical trials or in routine clinical care. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01419080.
Published: 2021

47. Harvesting Endothelial Cells During Routine Invasive Coronary Procedures

Author: John F. Beltrame, Anna A. Wawer, Chiara Murgia, Rosanna Tavella, Zinaida Tvorogova, Christopher Zeitz, Peter D. Zalewski, Sandra Hodge, A. Abdo, and Peter J. Psaltis
Subjects: Male, medicine.medical_specialty, Cardiac Catheterization, business.industry, Endothelial Cells, Middle Aged, Coronary Angiography, Surgery, Percutaneous Coronary Intervention, medicine, Humans, Female, Cardiology and Cardiovascular Medicine, business, Aged
Published: 2021

48. The LACE Index: A Predictor of Mortality and Readmission in Patients With Acute Myocardial Infarction

Author: Tracy Air, Clementine Labrosciano, Christopher Zeitz, Rosanna Tavella, John F. Beltrame, and Matthew I. Worthley
Subjects: medicine.medical_specialty, Index (economics), Receiver operating characteristic, business.industry, Health Policy, Mortality rate, Public Health, Environmental and Occupational Health, Australia, Myocardial Infarction, Discharged alive, Length of Stay, medicine.disease, Patient Readmission, Patient Discharge, Risk Factors, Emergency medicine, Cohort, Medicine, Humans, In patient, Myocardial infarction, business, Adverse effect, Emergency Service, Hospital, Retrospective Studies
Abstract: INTRODUCTION Improving patient outcomes after acute myocardial infarction (AMI) may be facilitated by identifying patients at a high risk of adverse events before hospital discharge. We aimed to determine the accuracy of the LACE (Length of stay, Acuity, Comorbidities, Emergency presentations within prior 6 months) index score (a prediction tool) for predicting 30-day all-cause mortality and readmission rates (independently and combined) in South Australian AMI patients who had an angiogram. METHODS All consecutive AMI patients enrolled in the Coronary Angiogram Database of South Australia Registry at two major tertiary hospitals and discharged alive between July 2016 to June 2017. A LACE score was calculated for each patient, and receiver operating characteristic curve analysis was performed. RESULTS Analysis of registry patients found a 30-day unplanned readmission rate of 11.8% and mortality rate of 0.7%. Moreover, the LACE index was a moderate predictor (C-statistic = 0.62) of readmissions in this cohort, and a score ≥10 indicated moderate discriminatory capacity to predict 30-day readmissions. CONCLUSION The LACE index shows moderate discriminatory capacity to predict 30-day readmissions and mortality. A cut-off score of nine to optimize sensitivity may assist clinicians in identifying patients at a high risk of adverse outcomes.
Published: 2021

49. In-hospital mode of death after out-of-hospital cardiac arrest

Author: Melanie R, Wittwer, Thomas, Armstrong, Jordan, Conway, Mohammed Ishaq, Ruknuddeen, Chris, Zeitz, John F, Beltrame, and Margaret A, Arstall
Subjects: Emergency Medicine, Emergency Nursing, Cardiology and Cardiovascular Medicine
Abstract: Factors associated with in-hospital mortality after out-of-hospital cardiac arrest (OHCA), such as mode of death and withdrawal of life-sustaining treatment (WLST), are not well established. This study aimed to compare clinical characteristics, timing of WLST and death, and precipitating aetiology between modes of death for OHCAs treated at hospital within a local health network.Retrospective cohort study of adult non-traumatic OHCAs included in a hospital based OHCA registry between 2011 and 2016 and deceased at hospital discharge, excluding cases retrieved to external hospitals. Mode of death was defined as (1) cardiovascular instability, (2) non-neurological WLST, (3) neurological WLST, and (4) formal brain death. Relevant data were extracted from the registry and stratified according to mode of death and timing of death as early (within the emergency department) or late (after admission).Mode of death data was available for 69 early and 144 late deaths. Cardiovascular instability was the primary mode for 75% of early deaths, while 72% of late deaths were attributed to neurological injury (47% neurological WLST and 24% brain death, combined). Cardiovascular instability was associated with cardiac aetiology, brain death was associated with younger age and highest rates of organ donation, and neurological WLST was associated with highest rates of targeted temperature management, and longest time from arrest to death (This is the first study to compare clinical characteristics of adult patients resuscitated from OHCA according to in-hospital mode of death. A consensus on the definition of mode of death with standardised classification is needed.
Published: 2022
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50. Predictors of Obstructive Sleep Apnoea (OSA) Population in the Coronary Angiogram Database of South Australia (CADOSA)

Author: Sharmalar Rajendran, Eng Lee Ooi, John F. Beltrame, Matthew I. Worthley, Rosanna Tavella, Christopher Zeitz, Tracy Air, Gnanadevan Mahadavan, Ajay Sinhal, and Margaret Arstall
Subjects: Male, Population, MEDLINE, Coronary Artery Disease, Disease, 030204 cardiovascular system & hematology, Coronary angiogram, Coronary Angiography, computer.software_genre, Chest pain, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, South Australia, Prevalence, Humans, Medicine, In patient, Angina, Stable, 030212 general & internal medicine, Risk factor, education, Male gender, Sleep Apnea, Obstructive, education.field_of_study, Database, business.industry, Australia, General Medicine, respiratory tract diseases, medicine.symptom, Cardiology and Cardiovascular Medicine, business, computer
Abstract: Obstructive sleep apnoea (OSA) is increasingly recognized to be a risk factor for cardiovascular disease. This study assessed the prevalence and clinical predictors of OSA in patients undergoing coronary angiography. Consecutive patients undergoing coronary angiography in South Australian public hospitals from 2015 to 2018 were included. Clinical details for consecutive patients undergoing coronary angiography in South Australian public hospitals were captured by the Coronary Angiogram Database of South Australia (CADOSA) registry staff, with OSA identified by patient report. Among the 9,885 patients undergoing coronary angiography for the investigation of chest pain, 11% (n = 1,089) were documented as having OSA. Independent clinical predictors of OSA included male gender (OR 2.22, 1.86-2.65, P0.001), diabetes mellitus (OR 1.84, 1.58-2.14, P0.001), depression (OR 1.81, 1.55-2.12, P0.001), prior heart failure (OR 1.63, 1.22-2.18, P = 0.001), hypertension (OR 1.61, 1.32-1.95, P ≤ 0.001), asthma (OR 1.61, 1.34-1.93, P0.001), not a current smoker (OR 1.60, 1.30-1.96, P0.001), dyslipidaemia (OR 1.46, 1.22-1.76, P0.001), non-acute coronary syndrome presentation (OR 1.45, 1.25-1.69, P0.001), chronic lung disease (OR 1.40, 1.12-1.73, P = 0.003), cerebrovascular disease (OR 1.36, 1.07-1.73, P = 0.012), non-obstructive coronary artery disease (NOCAD) (OR 1.30, 1.10-1.55, P = 0.003) and atrial fibrillation/flutter (OR 1.30, 1.06-1.60, P = 0.012). Finally, stable angina (32.1% vs 22.7%) and NOCAD (29.1% vs 26.3%, P = 0.051) were trended more common in patients with OSA versus no OSA. In addition to established risk factors for OSA, this study found NOCAD to be independent predictor of OSA; especially in those presenting with a stable angina presentation. This suggests that coronary vasomotor disorders may be associated with OSA, although further detailed studies are required.
Published: 2022
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