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1. Pericardial fat volume is related to endothelial-mediated coronary blood flow in women with suspected coronary microvascular dysfunction. A report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study

Author: Sofy Landes, Haider Aldiwani, Louise Thomson, Janet Wei, Ahmed Al-Badri, Puja K. Mehta, Michael Pedram, Manish Motwani, Galen Cook-Weins, George Sopko, Carl J. Pepine, C. Noel Bairey Merz, and Damini Dey
Subjects: Coronary microvascular dysfunction, Pericardial fat volume, Imaging biomarkers, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Coronary microvascular dysfunction is prevalent in women with signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) and is associated with an adverse prognosis. Elevated pericardial fat volume predicts adverse cardiac events, but mechanistic pathways of the association are not well understood. Methods: 118 women enrolled in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study with suspected coronary microvascular dysfunction but no obstructive CAD underwent adenosine stress 1.5 T cardiovascular magnetic resonance imaging (CMR) imaging and invasive coronary reactivity testing. Semi-quantitative myocardial perfusion reserve index (MPR) index was derived from perfusion images. Pericardial fat volume was measured by manually contouring the cardiac margins and adjacent adipose tissue on a single trans-axial HASTE slice at the level of the left main coronary artery origin and indexed to body surface-area. Simple standard deviation analysis obtained for continuous variables and frequency (percent) for categorical variables. The relationships between pericardial fat volume and coronary reactivity testing parameters were examined by correlation and multivariable regression analyses. Results: Women with suspected coronary microvascular dysfunction had a mean age of 55 ± 10 years, body mass index (BMI) of 28 ± 7 kg/m2, 44 % had a history of smoking, 63 % hypertension, 8 % diabetes, and 20 % dyslipidemia. CMR imaging-derived pericardial fat volume and coronary blood flow response to intracoronary acetylcholine (Δ CBF) were negatively correlated (r = −0.32, p = 0.0013). After adjustment for age, number of risk factors, high-density lipoprotein (HDL), and cold pressor diameter response, pericardial fat volume remained a significant predictor of Δ coronary blood flow (p = 0.04). There was no association with other coronary reactivity testing measures or CMRI derived MPR index. Conclusions: Among women with suspected coronary microvascular dysfunction but no obstructive CAD, pericardial fat volume appears to be related in a hypothesized adverse direction to coronary microvascular endothelial function. These results support further work confirming and extending these results to investigate pericardial fat volume as mechanistic pathway and potential treatment target for coronary microvascular dysfunction-related adverse events.Trial registration: clinicaltrials.gov NCT00832702.
Published: 2024
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2. Trends and Outcomes of ST‐Segment–Elevation Myocardial Infarction Among Young Women in the United States

Author: Temidayo Abe, Titilope Olanipekun, Demilade Adedinsewo, Oluseye Ogunmoroti, Ndausung Udongwo, Valery Effoe, Bria Rice, Ifeoma Onuorah, Jalal K. Ghali, Puja K. Mehta, and Erin D. Michos
Subjects: outcomes, ST‐elevation myocardial infarction, STEMI, trends, women, young, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Although there has been a decrease in the incidence of ST‐segment–elevation myocardial infarction (STEMI) in the United States, this trend might be stagnant or increasing in young women. We assessed the trends, characteristics, and outcomes of STEMI in women aged 18 to 55 years. Methods and Results We identified 177 602 women aged 18 to 55 with the primary diagnosis of STEMI from the National Inpatient Sample during years 2008 to 2019. We performed trend analyses to assess hospitalization rates, cardiovascular disease (CVD) risk factor profile, and in‐hospital outcomes stratified by three age subgroups (18–34, 35–44, and 45–55 years). We found STEMI hospitalization rates were decreased in the overall study cohort from 52 per 100 000 hospitalizations in 2008 to 36 per 100 000 in 2019. This was driven by decreased proportion of hospitalizations in women aged 45 to 55 years (74.2% to–71.7%; P
Published: 2023
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3. Chronic rheumatologic disorders and cardiovascular disease risk in women

Author: Puja K. Mehta, Rebecca D. Levit, Malissa J. Wood, Niti Aggarwal, Michelle L. O'Donoghue, S. Sam Lim, Kate Lindley, Scott Gaignard, Odayme Quesada, Nishant Vatsa, Ana Leon, Annabelle Santos Volgman, Waddah Malas, and Carl J. Pepine
Subjects: Inflammation, Women's heart disease, Autoimmune, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Cardiovascular disease (CVD) is a major health threat to women worldwide. In addition to traditional CVD risk factors, autoimmune conditions are increasingly being recognized as contributors to adverse CVD consequences in women. Chronic systemic autoimmune and inflammatory disorders can trigger premature and accelerated atherosclerosis, microvascular dysfunction, and thrombosis. The presence of comorbid conditions, duration of the autoimmune condition, disease severity, and treatment of underlying inflammation are all factors that impact CVD risk and progression. Early identification and screening of CVD risk factors in those with underlying autoimmune conditions may attenuate CVD in this population. Treatment with non-steroidal anti-inflammatory drugs, corticosteroids, disease modifying agents and biologics may influence CVD risk factors and overall risk. Multi-disciplinary and team-based care, clinical trials, and collaborative team-science studies focusing on systemic autoimmune conditions will be beneficial to advance care for women.
Published: 2023
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4. Evaluation and management of blood lipids through a woman's life cycle

Author: Jyoti Sharma, Jan McAlister, Niti R. Aggarwal, Janet Wei, Puja K. Mehta, Odayme Quesada, Deirdre Mattina, Nandita S. Scott, Erin D. Michos, Zainab Mahmoud, Karla Kurrelmeyer, Glaucia Maria Moraes De Oliveira, and Kathryn J. Lindley
Subjects: Lipids, Cholesterol management, Women, Diseases of the circulatory (Cardiovascular) system, RC666-701, Public aspects of medicine, RA1-1270
Abstract: There are currently no sex-specific guidelines for evaluation and management of blood lipids. While previous guidelines acknowledge sex-specific risk enhancing factors for lipid management in women for CVD prevention, this review focuses on how lipids are impacted during normal hormonal changes throughout a woman's life cycle- during adolescence, pre-pregnancy, pregnancy, pre- and perimenopause, menopause, and at older ages. In this review, the authors focus on management of primary prevention of CVD by examining sex-specific cardiovascular risk factors at each stage and pay special attention to statin use, statin side effects and non-statin therapies. Women need to understand their personalized cholesterol goals and ally with their clinicians to ensure successful management. Additionally, we highlight the biases that exist when treating dyslipidemia in women and the special care clinicians should take to ensure appropriate and aggressive therapies are made available to female patients. Finally, the authors recommend future research should focus on increasing enrollment of women in lipid trials. This is of paramount importance in discovering sex-specific difference in lipid management.
Published: 2022
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5. Socioeconomic characteristics of African American women attending community blood pressure screenings

Author: Telisa A. Spikes, Ijeoma Isiadinso, Puja K. Mehta, Sandra B. Dunbar, and Gina P. Lundberg
Subjects: African American women, Hypertension, Socioeconomic status, Blood pressure screenings, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Study objective: To examine the associations of education and income and blood pressure (BP) in a socioeconomically diverse cohort of African-American (AA) women attending community BP screenings. Design, setting, and participants: This cross-sectional analysis used data from AA women (n = 972) 53 ± 14 years, enrolled between 2015 and 2019 in the 10,000-women hypertension community screening project in the metropolitan Atlanta area. OLS linear regression were used to examine the associations between SES (education and income) and BP after adjusting for age, body mass index (BMI), smoking, and lipids. Main outcomes and measures: Outcomes were systolic and diastolic BP (SBP, DBP). Measures of SES included education [high school ≤(HS), some college, and ≥college] and income- [
Published: 2022
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6. Myocardial Infarction and Persistent Angina With No Obstructive Coronary Artery Disease

Author: Waddah Malas, MD, Ahmed AlBadri, MD, Janet Wei, MD, Puja K. Mehta, MD, R. David Anderson, MD, John Petersen, MD, Louise E. Thomson, MD, Carl J. Pepine, MD, and C. Noel Bairey Merz, MD
Subjects: coronary reactivity, endothelial function, MINOCA, persistent angina, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Women with myocardial infarction with no obstructive coronary artery disease (MINOCA) are increasingly recognized. Women with MINOCA are at high risk for major adverse cardiovascular events. In this case, we focus on the importance of early identification and management of MINOCA to improve patients’ angina and related quality of life. (Level of Difficulty: Beginner.)
Published: 2020
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7. Transcutaneous Cervical Vagal Nerve Stimulation in Patients with Posttraumatic Stress Disorder (PTSD): A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 Response to Stress

Author: J. Douglas Bremner, Matthew T. Wittbrodt, Nil Z. Gurel, MdMobashir H. Shandhi, Asim H. Gazi, Yunshen Jiao, Oleksiy M. Levantsevych, Minxuan Huang, Joy Beckwith, Isaias Herring, Nancy Murrah, Emily G. Driggers, Yi-An Ko, MhmtJamil L. Alkhalaf, Majd Soudan, Lucy Shallenberger, Allison N. Hankus, Jonathon A. Nye, Jeanie Park, Anna Woodbury, Puja K. Mehta, Mark H. Rapaport, Viola Vaccarino, Amit J. Shah, Bradley D. Pearce, and Omer T. Inan
Subjects: Mental healing, RZ400-408
Abstract: Background: Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress. Methods: Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI. Results: Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p
Published: 2021
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8. Gender-Related Differences in Chest Pain Syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine

Author: Puja K. Mehta, Janet Wei, Chrisandra Shufelt, Odayme Quesada, Leslee Shaw, and C. Noel Bairey Merz
Subjects: sex, gender, chest pain, coronary artery disease, INOCA, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Coronary artery disease (CAD) is the leading cause of morbidity and mortality among both women and men, yet women continue to have delays in diagnosis and treatment. The lack of recognition of sex-specific biological and socio-cultural gender-related differences in chest pain presentation of CAD may, in part, explain these disparities. Sex and gender differences in pain mechanisms including psychological susceptibility, the autonomic nervous system (ANS) reactivity, and visceral innervation likely contribute to chest pain differences. CAD risk scores and typical/atypical angina characterization no longer appear relevant and should not be used in women and men. Women more often have ischemia with no obstructive CAD (INOCA) and myocardial infarction, contributing to diagnostic and therapeutic equipoise. Existing knowledge demonstrates that chest pain often does not relate to obstructive CAD, suggesting a more thoughtful approach to percutaneous coronary intervention (PCI) and medical therapy for chest pain in stable obstructive CAD. Emerging knowledge regarding the central and ANS and visceral pain processing in patients with and without angina offers explanatory mechanisms for chest pain and should be investigated with interdisciplinary teams of cardiologists, neuroscientists, bio-behavioral experts, and pain specialists. Improved understanding of sex and gender differences in chest pain, including biological pathways as well as sociocultural contributions, is needed to improve clinical care in both women and men.
Published: 2021
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9. DETECTING HYPERTENSION AND IMPROVING HEALTHY LIFESTYLE IN AFRICAN AMERICAN WOMEN ATTENDING COMMUNITY SCREENING PROGRAM

Author: Waddah Malas, Puja K. Mehta, and Gina P. Lundberg
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701, Public aspects of medicine, RA1-1270
Published: 2021
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10. Cardiovascular Risk Factors in Younger Black Women: Results from the 10,000 Women Community Screening Project

Author: Nishant Vatsa, Aneesha Thobani, Laura Buendia, Karleigh Murphy, Senait Asier, Zhenchao Chen, Yi-An Ko, Tyler Putnam, Puja K. Mehta, and Gina P. Lundberg
Subjects: Familial hyperlipidemia, African American women, Cholesterol, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Cardiovascular Disease (CVD) risk factors are prevalent in black women, but when these risk factors arise is not clear. We aimed to determine when obesity, hypertension, and hyperlipidemia appear in black women within a community screening program. Methods: 945 black women who enrolled in the 10,000 Women community screening project in the metro Atlanta area were included (2015-2018). Socioeconomic, lifestyle, and traditional CVD risk factor information was patient-reported and measured. Characteristics of three cohorts stratified by age, 20-39 years old (yo), 40-59 yo, and ≥60 yo, were compared using pairwise analysis. Results: All cohorts had class 1 obesity. Mean systolic blood pressure was higher in older cohorts [20-39 yo: 122 ± 15; 40-59 yo: 133 ± 19; ≥60 yo: 142 ± 20 mmHg; p
Published: 2021
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11. Traditional and Emerging Sex-Specific Risk Factors for Cardiovascular Disease in Women

Author: Puja K. Mehta, Scott Gaignard, Arielle Schwartz, and JoAnn E. Manson
Subjects: heart disease, sex-specific risk factors, women, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Cardiovascular disease (CVD) remains a major health threat in women. While traditional CVD risk factors such as hypertension, hyperlipidemia, diabetes, and smoking have been recognized for over 50 years, optimal control of these risk factors remains a major challenge. Unique sex-specific risk factors such as adverse pregnancy outcomes, premature menopause and low estrogen states, and chronic autoimmune inflammatory disorders also contribute to increased CVD risk in women. In addition, psychological risk factors such as stress, depression, and social determinants of health may have a disproportionately adverse impact in women. An improved understanding of traditional and emerging sex-specific CVD risk factors and management of modifiable factors is critical for clinicians who provide care for women. Early recognition and treatment of risk factors may alter the trajectory of adverse CVD events. A multi-disciplinary approach with team-based care involving multiple specialists and improved, targeted educational efforts are needed to reduce CVD risk factors and its adverse consequences in women.
Published: 2022
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12. Left atrial mural endocarditis in the absence of significant structural heart disease

Author: Waddah Malas, Mashaal Ikram, Max Ruge, Puja K. Mehta, and Stuart Chen
Subjects: Endocarditis, Left atrium, Echocardiogram, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Primary mural endocarditis without valvular involvement is rare and most often involves the ventricular endocardium. Left atrial mural endocarditis is an extremely rare subset of infective endocarditis. We describe a case of a young woman with left atrial mural endocarditis without significant structural or valvular heart disease.
Published: 2021
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13. Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1‐Year Follow‐Up: Results From WISE‐CVD

Author: Odayme Quesada, Melody Hermel, Nissi Suppogu, Haider Aldiwani, Chrisandra Shufelt, Puja K. Mehta, Galen Cook‐Wiens, Jenna Maughan, Daniel S. Berman, Louise E. J. Thomson, Eileen M. Handberg, Carl J. Pepine, C. Noel Bairey Merz, and Janet Wei
Subjects: angina, cardiovascular magnetic resonance imaging, ischemic heart disease, left ventricular remodeling, quality of life, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Women with ischemia and no obstructive coronary artery disease are increasingly recognized and found to be at risk for major adverse cardiovascular events. Methods and Results In 214 women with suspected ischemia and no obstructive coronary artery disease who completed baseline and 1‐year follow‐up vasodilatory stress cardiac magnetic resonance imaging, we investigated temporal trends in angina (Seattle Angina Questionnaire [SAQ]), myocardial perfusion reserve index, blood pressure, and left ventricular (LV) remodeling and function from baseline to 1‐year follow‐up and explored associations between these different parameters. We observed concordant positive trends in 4/5 SAQ domains, SAQ‐7, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to‐volume ratio. There was no association between SAQ‐7 improvement and myocardial perfusion reserve index improvement over 1‐year follow‐up (P=0.1). Higher indexed LV end‐diastolic volume and time to peak filling rate at baseline were associated with increased odds of clinically relevant SAQ‐7 improvement (odds ratio [OR], 1.05; 95% CI, 1.0–1.1; and OR, 2.40; 95% CI, 1.1–5.0, respectively). Hypertension was associated with decreased odds of SAQ‐7 improvement (OR, 0.41; 95% CI, 0.19–0.91). Conclusions In women with ischemia and no obstructive coronary artery disease clinically treated with cardiac medications over 1 year, we observed concurrent temporal trends toward improvement in SAQ, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to volume ratio. We showed that abnormalities in LV morphology and diastolic function at baseline were predictive of clinically significant improvement in angina at follow‐up, whereas history of hypertension was associated with lower odds. Future studies are needed to assess the mechanisms and treatments responsible for the improvements we observed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02582021.
Published: 2020
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14. Oxidative Stress Is Associated With Diastolic Dysfunction in Women With Ischemia With No Obstructive Coronary Artery Disease

Author: Mohamad Raad, Ahmed AlBadri, Janet Wei, Puja K. Mehta, Jenna Maughan, Adit Gadh, Louise Thomson, Dean P. Jones, Arshed A. Quyyumi, Carl J. Pepine, and C. Noel Bairey Merz
Subjects: cardiac MRI, diastolic dysfunction, INOCA, oxidative stress, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have evidence of diastolic dysfunction. Oxidative stress (OS) is associated with cardiovascular risk factors and adverse outcomes. The relationship between systemic OS and diastolic dysfunction is unknown. Methods and Results A subgroup of women (n=75) with suspected ischemia and no obstructive coronary artery disease who had both cardiac magnetic resonance imaging and OS measurements were enrolled in the WISE‐CVD (Women Ischemia Syndrome Evaluation—Coronary Vascular Dysfunction) study. Left ventricular end‐diastolic pressure was measured invasively. Left ventricular end‐diastolic volume and peak filling rate were assessed using cardiac magnetic resonance imaging. Aminothiol levels of plasma cystine and glutathione were measured as markers of OS. Spearman correlation and linear regression analyses were conducted. The group mean age was 54±11 years, and 61% had a resting left ventricular end‐diastolic pressure >12 mm Hg. Cystine levels correlated negatively with the peak filling rate (r=−0.31, P=0.007) and positively with left ventricular end‐diastolic pressure (r=0.25; P=0.038), indicating that increased OS was associated with diastolic dysfunction. After multivariate adjustment including multiple known risk factors for diastolic dysfunction and cardiovascular medications, cystine levels continued to be associated with peak filling rate (β=−0.27, P=0.049) and left ventricular end‐diastolic pressure (β=0.25; P=0.035). Glutathione levels were not associated with indices of diastolic function. Conclusions OS, measured by elevated levels of cystine, is associated with diastolic dysfunction in women with evidence of ischemia and no obstructive coronary artery disease, indicating the role of OS in patients with ischemia and no obstructive coronary artery disease. Its role in the progression of heart failure with preserved ejection fraction should be explored further.
Published: 2020
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15. Not typical angina and mortality in women with obstructive coronary artery disease: Results from the Women’s Ischemic Syndrome Evaluation study (WISE)

Author: Erika Jones, B. Delia Johnson, Leslee J. Shaw, May Bakir, Janet Wei, Puja K. Mehta, Margo Minissian, Carl J. Pepine, Steven E. Reis, Sheryl F. Kelsey, Eileen Handberg, Vera Bittner, George Sopko, and C. Noel Bairey Merz
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Women frequently present with symptoms not typical of angina (NTA) making ischemic heart disease recognition, diagnosis and treatment challenging. We compared mortality in women with obstructive coronary artery disease (CAD) with NTA vs typical angina (TA). Methods: We studied 326 Women’s Ischemia Syndrome Evaluation (WISE) participants undergoing coronary angiography for suspected myocardial ischemia with core-lab measured obstructive CAD. TA was defined as sub-sternal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin; NTA did not meet criteria for TA. The women were followed for non-fatal events and death for a median of 5.9 and 9.6 years respectively. Multivariate cox proportional hazards regression determined relations to events. Results: Overall, 115 (35%) of the women had TA. Baseline demographics, risk factors or additional symptom characteristics were similar between the two angina groups. Non-fatal events did not differ between groups. Women with NTA had a higher mortality compared to TA women (36% vs 26%, respectively, p = 0.047). Despite adjustment for additional major risk variables, NTA was an independent predictor of mortality compared to TA with a hazard ratio of 1.73 (95% Confidence interval: 1.04, 2.89). Conclusions: Among women with suspected ischemia undergoing coronary angiography with obstructive CAD, NTA was more common than TA, and predicted a higher longer-term mortality. Further investigation is needed to confirm these results, and investigate potential explanations for the higher mortality observed in women with NTA women, including lower recognition or action in the setting of obstructive CAD. Keywords: Angina, Coronary artery disease, Mortality
Published: 2020
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16. Soluble Urokinase‐Type Plasminogen Activator Receptor and High‐Sensitivity Troponin Levels Predict Outcomes in Nonobstructive Coronary Artery Disease

Author: Ahmed Al‐Badri, Ayman Samman Tahhan, Nabil Sabbak, Ayman Alkhoder, Chang Liu, Yi‐An Ko, Viola Vaccarino, Afif Martini, Arianna Sidoti, Cydney Goodwin, Bahjat Ghazzal, Agim Beshiri, Gillian Murtagh, Puja K. Mehta, and Arshed A. Quyyumi
Subjects: adverse outcomes, angina, hsTnI, INOCA, ischemia, no obstructive coronary artery disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase‐type plasminogen activator receptor) and hsTnI (high‐sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All‐cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow‐up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all‐cause death (hazard ratio=3.2 [95% CI, 1.8–5.7] and 1.3 [95% CI, 1.0–1.7], respectively; both P
Published: 2020
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17. Angina Hospitalization Rates in Women With Signs and Symptoms of Ischemia But no Obstructive Coronary Artery Disease: A Report from the WISE (Women's Ischemia Syndrome Evaluation) Study

Author: Haider Aldiwani, Melody Zaya, Nissi Suppogu, Odayme Quesada, B. Delia Johnson, Puja K. Mehta, Chrisandra Shufelt, John Petersen, Babak Azarbal, Bruce Samuels, R. David Anderson, Leslee J. Shaw, Saibal Kar, Eileen Handberg, Sheryl F. Kelsey, Carl J. Pepine, and C. Noel Bairey Merz
Subjects: angina, coronary artery disease, hospitalization, women, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Recurrent hospitalization is prevalent in women with signs and symptoms of ischemia and no obstructive coronary artery disease. We hypothesized that rates of angina hospitalization might have changed over time, given advances in diagnostic and therapeutic approaches. Methods and Results We evaluated 551 women enrolled in the WISE (Women's Ischemia Syndrome Evaluation) study with no obstructive coronary artery disease (CAD) for a follow‐up period of 9.1 years. We analyzed angina hospitalization rates using the Kaplan‐Meier method. Univariate analysis and multivariable Cox proportional hazard models were developed for prediction of angina hospitalization in women with signs and symptoms of angina and no CAD. A total of 223 women had nonobstructive CAD (>20–50%
Published: 2020
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18. Phosphodiesterase type 5 inhibition may reduce diastolic function in women with ischemia but no obstructive coronary artery disease

Author: Michael D. Nelson, Puja K. Mehta, Janet Wei, Behzad Sharif, Louise E. J. Thomson, Daniel Berman, Debiao Li, and C. Noel Bairey Merz
Subjects: Women’s ischemic syndrome, Coronary microvascular dysfunction, Diastolic dysfunction, Myocardial perfusion reserve index, Phosphodiesterase type 5 inhibition, Medicine
Abstract: Abstract Background Ischemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive. Methods To address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease. Left ventricular morphology and function, along with myocardial perfusion reserve index, were assessed by contrast-enhanced cardiac magnetic resonance imaging. Results A total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment. Her symptoms resolved after cessation of the study medication. In contrast to our hypothesis, phosphodiesterase type 5 inhibition reduced the rate of circumferential strain in diastole in all four women who completed the trial (that is, diastolic dysfunction). This impairment could not be explained by changes in heart rate, contractility, blood pressure, or preload, and was not associated with a change in myocardial perfusion reserve index. Frequency of angina also tended to increase with treatment, with the greatest increase occurring in the patient with the greatest impairment in diastolic strain. Conclusions Taken together, these data question the efficacy of phosphodiesterase type 5 inhibition to treat women with ischemic heart disease, and highlight the need for further investigation.
Published: 2017
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19. Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction (WISE-CVD)

Author: R. David Anderson, John W. Petersen, Puja K. Mehta, Janet Wei, B. Delia Johnson, Eileen M. Handberg, Saibal Kar, Bruce Samuels, Babak Azarbal, Kamlesh Kothawade, Sheryl F. Kelsey, Barry Sharaf, Leslee J. Shaw, George Sopko, C. Noel Bairey Merz, and Carl J. Pepine
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Objective. In a separate, contemporary cohort, we sought to confirm findings of the original Women’s Ischemia Syndrome Evaluation (WISE). Background. The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. Methods. We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or
Published: 2019
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20. Berries and Their Polyphenols as a Potential Therapy for Coronary Microvascular Dysfunction: A Mini-Review

Author: Rami S. Najjar, Arielle M. Schwartz, Brett J. Wong, Puja K. Mehta, and Rafaela G. Feresin
Subjects: ischemic heart disease, endothelial dysfunction, microvascular, berries, polyphenols, inflammation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Ischemia with no obstructive coronary artery disease (INOCA) is a common diagnosis with a higher prevalence in women compared to men. Despite the absence of obstructive coronary artery disease and no structural heart disease, INOCA is associated with major adverse cardiovascular outcomes as well a significant contributor to angina and related disability. A major feature of INOCA is coronary microvascular dysfunction (CMD), which can be detected by non-invasive imaging and invasive coronary physiology assessments in humans. CMD is associated with epicardial endothelial-dependent and -independent dysfunction, diffuse atherosclerosis, and left-ventricular hypertrophy, all of which lead to insufficient blood flow to the myocardium. Inflammatory and oxidative stress signaling, upregulation of the renin-angiotensin-aldosterone system and adrenergic receptor signaling are major drivers of CMD. Treatment of CMD centers around addressing cardiovascular risk factors; however, there are limited treatment options for those who do not respond to traditional anti-anginal therapies. In this review, we highlight the ability of berry-derived polyphenols to modulate those pathways. The evidence supports the need for future clinical trials to investigate the effectiveness of berries and their polyphenols in the treatment of CMD in INOCA patients.
Published: 2021
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21. Meditation and Cardiovascular Risk ReductionA Scientific Statement From the American Heart Association

Author: Glenn N. Levine, Richard A. Lange, C. Noel Bairey‐Merz, Richard J. Davidson, Kenneth Jamerson, Puja K. Mehta, Erin D. Michos, Keith Norris, Indranill Basu Ray, Karen L. Saban, Tina Shah, Richard Stein, and Sidney C. Smith
Subjects: AHA Scientific Statements, cardiovascular disease, cardiovascular risk, meditation, primary prevention, secondary prevention, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Despite numerous advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains a leading cause of morbidity and mortality. Novel and inexpensive interventions that can contribute to the primary and secondary prevention of cardiovascular disease are of interest. Numerous studies have reported on the benefits of meditation. Meditation instruction and practice is widely accessible and inexpensive and may thus be a potential attractive cost‐effective adjunct to more traditional medical therapies. Accordingly, this American Heart Association scientific statement systematically reviewed the data on the potential benefits of meditation on cardiovascular risk. Neurophysiological and neuroanatomical studies demonstrate that meditation can have long‐standing effects on the brain, which provide some biological plausibility for beneficial consequences on the physiological basal state and on cardiovascular risk. Studies of the effects of meditation on cardiovascular risk have included those investigating physiological response to stress, smoking cessation, blood pressure reduction, insulin resistance and metabolic syndrome, endothelial function, inducible myocardial ischemia, and primary and secondary prevention of cardiovascular disease. Overall, studies of meditation suggest a possible benefit on cardiovascular risk, although the overall quality and, in some cases, quantity of study data are modest. Given the low costs and low risks of this intervention, meditation may be considered as an adjunct to guideline‐directed cardiovascular risk reduction by those interested in this lifestyle modification, with the understanding that the benefits of such intervention remain to be better established. Further research on meditation and cardiovascular risk is warranted. Such studies, to the degree possible, should utilize randomized study design, be adequately powered to meet the primary study outcome, strive to achieve low dropout rates, include long‐term follow‐up, and be performed by those without inherent bias in outcome.
Published: 2017
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22. Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study

Author: Puja K. Mehta, B. Delia Johnson, Tanya S. Kenkre, Wafia Eteiba, Barry Sharaf, Carl J. Pepine, Steven E. Reis, William J. Rogers, Sheryl F. Kelsey, Diane V. Thompson, Vera Bittner, George Sopko, Leslee J. Shaw, and C. Noel Bairey Merz
Subjects: coronary atherosclerosis, ischemic heart disease, sudden cardiac death, women, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundSudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. Methods and ResultsOverall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P
Published: 2017
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23. Takotsubo syndrome: A current review of presentation, diagnosis, and management

Author: Monica, Li, Christopher N, Nguyen, Olga, Toleva, and Puja K, Mehta
Subjects: Obstetrics and Gynecology, General Biochemistry, Genetics and Molecular Biology
Abstract: Takotsubo syndrome is a syndrome of acute heart failure due to left ventricular systolic dysfunction that is associated with increased cardiovascular morbidity and mortality. It occurs in both sexes and at all ages, but predominates in post-menopausal women for reasons that are unclear. In a patient who presents with cardiac symptoms, electrocardiographic changes, and/or biomarker elevation indicating myocardial stress (i.e. troponin elevation), this condition should be considered in the differential diagnosis. Cardiac imaging is critical for a timely diagnosis of this condition and has management implications. This syndrome can occur with or without underlying coronary artery disease, and while there are various characteristic myocardial patterns described on imaging, the most common one is left ventricular dysfunction due to apical stunning with basal hyperkinesis. In the acute phase, Takotsubo syndrome can lead to life-threatening sequelae, including cardiogenic shock, pulmonary edema, thromboembolism, and arrhythmias. Multiple pathophysiologic mechanisms are implicated, including an acute increase in left ventricular afterload in the setting of sympathetic activation with a catecholamine storm, multi-vessel coronary vasospasm, coronary endothelial microvascular dysfunction, and inflammation. In this review, we discuss the current knowledge surrounding presentation, diagnosis, and treatment of this under-diagnosed condition.
Published: 2022

24. Mental Stress-Induced Myocardial Ischemia

Author: Puja K. Mehta, Ashish Sharma, J. Douglas Bremner, and Viola Vaccarino
Subjects: Cardiology and Cardiovascular Medicine
Abstract: To summarize recent evidence on mental stress-induced myocardial ischemia (MSIMI), its mechanisms, and clinical significance.MSIMI can occur in patients with normal cardiac stress testing, is only weakly related to severity of coronary artery disease (CAD), and it is often silent. Among patients with CAD, MSIMI is associated with a twofold increased risk of major adverse cardiovascular events compared to those who do not have MSIMI. Certain groups such as young women with myocardial infarction and those with psychological comorbidities are more susceptible to MSIMI. Abnormal microvascular vasoreactivity and inflammation are implicated mechanisms in MSIMI. Increased brain activity in regions that modulate autonomic reactivity to emotional stress and fear is associated with MSIMI. MSIMI has important prognostic implications in patients with CAD. Stress can no longer be ignored as a risk factor in cardiology care. Clinical trials testing effective strategies to target MSIMI are needed.
Published: 2022

25. INOCA and MINOCA: Are Women’s Heart Centres the Answer to Understanding and Management of These Increasing Populations of Women (and Men)?

Author: Christine Pacheco, Judy Luu, Puja K. Mehta, Janet Wei, Martha Gulati, and C. Noel Bairey Merz
Subjects: Male, MINOCA, Humans, Female, Heart, Cardiology and Cardiovascular Medicine, Article
Published: 2022

26. Ischemic Heart Disease in Young Women

Author: Margo B. Minissian, Puja K. Mehta, Sharonne N. Hayes, Ki Park, Janet Wei, C. Noel Bairey Merz, Leslie Cho, Annabelle Santos Volgman, Islam Y. Elgendy, Mamas Mamas, Melinda B. Davis, Harmony R. Reynolds, Kelly Epps, Kathryn Lindley, Malissa Wood, Odayme Quesada, Gregory Piazza, and Carl J. Pepine
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022

27. Mechanisms of Coronary Ischemia in Women

Author: Jingwen Huang, Sonali Kumar, Olga Toleva, and Puja K. Mehta
Subjects: Myocardial Infarction, Myocardial Ischemia, Humans, Female, Coronary Artery Disease, Coronary Angiography, Cardiology and Cardiovascular Medicine, Coronary Vessels, Troponin
Abstract: Obstructive coronary artery disease is a major cause of ischemia in both men and women; however, women are more likely to present with ischemia in the setting of no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA), conditions that are associated with adverse cardiovascular prognosis despite absence of coronary stenosis. In this review, we focus on mechanisms of coronary ischemia that should be considered in the differential diagnosis when routine anatomic clinical investigation leads to the finding of non-obstructive coronary artery disease on coronary angiography in the setting of acute myocardial infarction.There are multiple mechanisms that contribute to MINOCA, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction (CMD), coronary embolism and/or thrombosis, and spontaneous coronary artery dissection. Non-coronary causes such as myocarditis or supply-demand mismatch should also be considered on the differential when there is an unexplained troponin elevation. Use of advanced imaging and diagnostic techniques to determine the underlying etiology of MINOCA is feasible and helpful, as this has the potential to guide management and secondary prevention. Failure to identify the underlying cause(s) may result in inappropriate treatment and inaccurate counseling to patients. MINOCA predominates in young women and is associated with a guarded prognosis. The diagnosis of MINOCA should prompt further investigation to determine the underlying cause of troponin elevation. Patients with INOCA and MINOCA are heterogeneous, and response to treatments can be variable. Large randomized controlled trials to determine longer-term optimal medical therapy for management of these conditions are under investigation.
Published: 2022

28. Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Author: Samaah Sullivan, An Young, Mariana Garcia, Zakaria Almuwaqqat, Kasra Moazzami, Muhammad Hammadah, Bruno B. Lima, Yingtian Hu, Mohamad Nour Jajeh, Ayman Alkhoder, Lisa Elon, Tené T. Lewis, Amit J. Shah, Puja K. Mehta, J. Douglas Bremner, Arshed A. Quyyumi, and Viola Vaccarino
Subjects: Cardiology and Cardiovascular Medicine
Abstract: Background: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. Methods: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. Results: Of 263 patients (the mean age was 51 years; range, 25–61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05–2.13]; P =0.03) among women only (sex interaction: P =0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07–1.71]; P =0.01), and the association was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.
Published: 2023

29. It Takes a Village: Expanding Women’s Cardiovascular Care to Include the Community as well as Cardiovascular and Primary Care Teams

Author: Ijeoma Isiadinso, Puja K. Mehta, Stacy Jaskwhich, and Gina P. Lundberg
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022

30. Abstract P407: Sex Differences in Microvascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Author: Samaah Sullivan, An Young, Mariana Garcia, Zakaria Almuwaqqat, Kasra Moazzami, Muhammad Hammadah, Bruno B Lima, Yingtian Hu, Mhmtjamil Alkhalaf, Mohamad Nour Jajeh, Ayman Alkhoder, Lisa Elon, Tene T Lewis, Amit J Shah, Puja K Mehta, J Douglas Bremner, Arshed A Quyyumi, and Viola Vaccarino
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Microvascular dysfunction during acute mental stress may be an important determinant of major adverse cardiovascular outcomes (MACE) especially among middle-aged women survivors of an acute myocardial infarction (MI). Hypothesis: There are sex differences in the association between microvascular dysfunction and MACE. Methods: The Myocardial Infarction and Mental Stress Study 2 enrolled individuals who had been hospitalized for an MI in the past 8 months at the age of 60 years or younger, with an oversampling of women. Reactive hyperemia index (RHI) was used to measure digital microvascular function before and 30 minutes after a public-speaking mental stress task. This assessment was contrasted with macrovascular endothelial function at the brachial artery through flow-mediated dilation (FMD). Participants were followed for 5-years, and MACE was defined as a composite of cardiovascular death, first/recurring events for nonfatal MI, and hospitalizations for heart failure. Cox proportional hazards models were used to examine vascular response to stress (difference between post-stress and resting values) and MACE adjusting for demographics, clinical risk factors, medications, psychological factors, and mental stress ischemia. Lower RHI and FMD values are indicative of greater microvascular and endothelial dysfunction, respectively. Results: Of 263 participants, the mean age was 51 years and 48% were women. There were 64 patients with 141 adverse cardiovascular events (first and repeated). In the overall sample, there was no significant association between microvascular response to stress and MACE, but there was a significant interaction with sex (p = 0.03). Each standard deviation decrease in RHI response to stress was associated with 50% greater risk of MACE (HR: 1.50, 95% CI: 1.05, 2.13) among women only, while no association was observed in men (HR 0.93, 95% CI: 0.69, 1.26). Transient endothelial dysfunction in response to stress (for each standard deviation decrease in FMD) was associated with 35% greater risk of MACE (HR: 1.35; 95% CI: 1.07, 1.71), and was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress is associated with MACE among women but not among men. In contrast, brachial artery endothelial dysfunction is similarly related to MACE among both men and women. These results suggest that microvascular dysfunction is a female-specific mechanism linking psychological stress to adverse outcomes.
Published: 2023

31. Cardiovascular Implications of Immune Disorders in Women

Author: Caitlin A. Moran, Lauren F. Collins, Nour Beydoun, Puja K. Mehta, Yetunde Fatade, Ijeoma Isiadinso, Tené T. Lewis, Brittany Weber, Jill Goldstein, Igho Ofotokun, Arshed Quyyumi, May Y. Choi, Kehmia Titanji, and Cecile D. Lahiri
Subjects: Immune System Diseases, Cardiovascular Diseases, Physiology, Humans, bacteria, Female, HIV Infections, Adaptive Immunity, biochemical phenomena, metabolism, and nutrition, Gonadal Steroid Hormones, Cardiology and Cardiovascular Medicine, Hepatitis C, Article
Abstract: Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female-predominant), HIV (male-female equivalent), and HCV (male-predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.
Published: 2022

32. Path analysis of the impact of prenatal alcohol on adult vascular function

Author: Julie A. Kable, Puja K. Mehta, Fauzia Rashid, and Claire D. Coles
Subjects: Psychiatry and Mental health, Medicine (miscellaneous), Toxicology
Abstract: The vascular system may be particularly vulnerable to prenatal alcohol exposure (PAE). Alterations in angiogenesis and epigenetic changes to vascular development have been implicated as a probable mechanism for this vulnerability.We assessed the long-term impact of prenatal alcohol exposure (PAE) on adult vascular health using a prospective cohort first identified while in utero. Participants with no PAE (n = 37, mean age = 36.7 [SD = 1.6] years) were compared to participants with PAE (n = 51, mean age = 36.3 [SD = 1.7] years). Their vascular health was assessed by arterial blood pressure (BP) and peripheral arterial tonometry, which yields an index of endothelial function (reactive hyperemia index) and a measure of arterial stiffness (augmentation index). Blood samples were collected to assess cholesterol levels and insulin resistance (glucose, hemoglobin A1C, and insulin). Path analysis was used to examine the direct and indirect effects of PAE on vascular health after adjusting for other known physical outcomes.Participants with a history of PAE weighed less, trended towards being shorter, had smaller body mass, and had more alcohol-related dysmorphic features than those without PAE. Path analysis suggested that the impact of PAE on BP was through its indirect relationships with height, body mass index, and dysmorphic features and resulted in protective effects relative to the Contrast group who were disproportionately overweight. PAE was also found to have a direct negative effect on endothelial function. An index of total alcohol-related dysmorphic features was negatively had both a direct effect on arterial stiffness and an indirect effect on endothelial function.Prenatal alcohol exposures' impact on vascular function is not independent of other common physical and environmental factors but endothelial function and arterial stiffness seemed most compromised after controlling for these other factors. Level of alcohol-related dysmorphic features seems to be predictive of more adverse effects than endothelial function and vascular stiffness.
Published: 2022

33. Brain-heart connections in stress and cardiovascular disease: Implications for the cardiac patient

Author: Paolo Raggi, J. Douglas Bremner, Brad D. Pearce, Puja K. Mehta, Viola Vaccarino, Arshed A. Quyyumi, and Amit J. Shah
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocardial ischemia, Provocation test, Myocardial Ischemia, Disease, 030204 cardiovascular system & hematology, Cardiovascular System, Article, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), medicine, Humans, Myocardial infarction, Intensive care medicine, business.industry, Brain, Heart, medicine.disease, Cardiovascular physiology, 030104 developmental biology, Cardiovascular Diseases, Etiology, Female, Cardiology and Cardiovascular Medicine, business, Psychosocial, Stress, Psychological
Abstract: The influence of psychological stress on the physiology of the cardiovascular system, and on the etiology and outcomes of cardiovascular disease (CVD) has been the object of intense investigation. As a whole, current knowledge points to a “brain-heart axis” that is especially important in individuals with pre-existing CVD. The use of acute psychological stress provocation in the laboratory has been useful to clarify the effects of psychological stress on cardiovascular physiology, immune function, vascular reactivity, myocardial ischemia, neurobiology and cardiovascular outcomes. An emerging paradigm is that dynamic perturbations of physiological and molecular pathways during stress or negative emotions are important in influencing cardiovascular outcomes, and that some patient subgroups, such as women, patients with an early-onset myocardial infarction, and patients with adverse psychosocial exposures, may be at especially high risk for these effects. This review summarizes recent knowledge on mind-body connections in CVD among cardiac patients and highlights important pathways of risk which could become the object of future intervention efforts. As a whole, this research suggests that an integrated study of mind and body is necessary to fully understand the determinants and consequences of CVD.
Published: 2021

34. 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 Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, 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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Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, 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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, and 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, 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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 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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 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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 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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 Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, 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, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020

35. 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

36. Management of Women With Acquired Cardiovascular Disease From Pre-Conception Through Pregnancy and Postpartum

Author: Rashmee U. Shah, C. Noel Bairey Merz, Natalie A. Bello, Melinda B. Davis, Islam Y. Elgendy, Keith C. Ferdinand, Annabelle Santos Volgman, Dipti Itchhaporia, Janet Wei, Puja K. Mehta, Nanette K. Wenger, Andrea M. Russo, Ki Park, Afshan B. Hameed, Claire S. Duvernoy, Harmony R. Reynolds, Kathryn J. Lindley, Carl J. Pepine, and Margo Minissian
Subjects: medicine.medical_specialty, Pregnancy, business.industry, Cardiovascular risk factors, Cardiomyopathy, Maternal morbidity, Disease, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Acute management, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Abstract: Acquired cardiovascular conditions are a leading cause of maternal morbidity and mortality. A growing number of pregnant women have acquired and heritable cardiovascular conditions and cardiovascular risk factors. As the average age of childbearing women increases, the prevalence of acute coronary syndromes, cardiomyopathy, and other cardiovascular complications in pregnancy are also expected to increase. This document, the third of a 5-part series, aims to provide practical guidance on the management of such conditions encompassing pre-conception through acute management and considerations for delivery.
Published: 2021

37. Left ventricular circumferential strain and coronary microvascular dysfunction: A report from the Women's Ischemia Syndrome Evaluation Coronary Vascular Dysfunction (WISE-CVD) Project

Author: Eileen M. Handberg, John W. Petersen, C. Noel Bairey Merz, Balaji Tamarappoo, Ahmed AlBadri, Carl J. Pepine, Louise Thomson, T. Jake Samuel, Janet Wei, Susan Cheng, Haider Aldiwani, Michael D. Nelson, Behzad Sharif, Omeed Elboudwarej, and Puja K. Mehta
Subjects: medicine.medical_specialty, Heart Ventricles, Myocardial Ischemia, Ischemia, Coronary Artery Disease, 030204 cardiovascular system & hematology, Article, Coronary artery disease, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Coronary Circulation, Internal medicine, medicine, Humans, Circumferential strain, 030212 general & internal medicine, business.industry, Perfusion reserve, Coronary Microvascular Disease, medicine.disease, Cardiology, Feature tracking, Female, Cardiology and Cardiovascular Medicine, business, Cardiac magnetic resonance
Abstract: AIMS: Women with ischemia but no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD). Left ventricular (LV) circumferential strain (CS) is often lower in INOCA compared to healthy controls; however, it remains unclear whether CS differs between INOCA women with and without CMD. We hypothesized that CS would be lower in women with CMD, consistent with CMD-induced LV mechanical dysfunction. METHODS AND RESULTS: Cardiac magnetic resonance (cMR) images were examined from women enrolled in the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project. CS by feature tracking in INOCA women with CMD, defined as myocardial perfusion reserve index (MPRI)
Published: 2021

38. Alterations in Insulin Levels in Adults with Prenatal Alcohol Exposure

Author: Claire D. Coles, Julie A. Kable, and Puja K. Mehta
Subjects: Adult, Blood Glucose, animal structures, Alcohol Drinking, medicine.medical_treatment, 030508 substance abuse, Medicine (miscellaneous), Physiology, Carbohydrate metabolism, Toxicology, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Pregnancy, Diabetes mellitus, Humans, Insulin, Medicine, Prospective Studies, Prospective cohort study, business.industry, medicine.disease, Black or African American, Psychiatry and Mental health, Prenatal Exposure Delayed Effects, Homeostatic model assessment, Female, Insulin Resistance, 0305 other medical science, business, Body mass index, 030217 neurology & neurosurgery
Abstract: OBJECTIVE Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences. METHOD A prospective cohort of predominantly African-American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA-IR) was also computed. Body mass index (BMI) was calculated and normal defined as
Published: 2021

39. Ivabradine in Cardiovascular Disease Management Revisited: a Review

Author: Christopher Chen, Sripal Bangalore, Doralisa Morrone, Puja K. Mehta, Lucas C. Godoy, Gurleen Kaur, and Mandeep S. Sidhu
Subjects: 0301 basic medicine, medicine.medical_specialty, Myocardial Ischemia, Heart failure, Disease, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Tachycardia, Internal medicine, Heart rate, Humans, Medicine, Ivabradine, Pharmacology (medical), Prospective Studies, Sinus, Randomized Controlled Trials as Topic, Pharmacology, Ejection fraction, business.industry, Sinoatrial node, Inappropriate sinus tachycardia, Stable ischemic heart disease, Cardiovascular Agents, Cardiovascular Diseases, Stroke Volume, Tachycardia, Sinus, General Medicine, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Cardiology, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.
Published: 2021

40. EPICARDIAL ADIPOSE TISSUE ATTENUATION ON COMPUTED TOMOGRAPHY IN WOMEN WITH CORONARY MICROVASCULAR DYSFUNCTION: A PILOT, HYPOTHESIS GENERATING STUDY

Author: Yetunde A. Fatade, Esha Dave, John Archer, Fauzia Rashid, Nishant Vatsa, Carlo Nicola De Cecco, Puja K. Mehta, and Arthur E. Stillman
Subjects: Cardiology and Cardiovascular Medicine
Published: 2023

41. THE 10,000 WOMEN PROJECT: A GLANCE AT CARDIOVASCULAR HEALTH OF BLACK WOMEN DURING COMMUNITY SCREENING

Author: Rand Ibrahim, Telisa Spikes, Stacy H. Jaskwhich, Puja K. Mehta, and Gina Price Lundberg
Subjects: Cardiology and Cardiovascular Medicine
Published: 2023

42. Cardiac Sympathetic Activity by 123I-Meta-Iodobenzylguanidine Imaging in Women With Coronary Microvascular Dysfunction

Author: Lian Li, C. Noel Bairey Merz, Michael D. Nelson, Melody H. Hermel, Janet Wei, Odayme Quesada, Louise Thomson, Sean W. Hayes, Piotr J. Slomka, Mark I. Travin, Michael R. Irwin, David S. Krantz, Leslee J. Shaw, Daniel S. Berman, Carl J. Pepine, David Hermel, John D. Friedman, Amanda Swift, and Puja K. Mehta
Subjects: medicine.medical_specialty, Sympathetic Nervous System, business.industry, MEDLINE, Meta iodobenzylguanidine, Heart, Pilot Projects, Sympathetic activity, Article, Iodine Radioisotopes, 3-Iodobenzylguanidine, Text mining, Predictive Value of Tests, Internal medicine, medicine, Cardiology, Humans, Female, Radiology, Nuclear Medicine and imaging, Radiopharmaceuticals, Cardiology and Cardiovascular Medicine, business
Published: 2021

43. The black box of coronary microcirculation: Is it at the tip of the finger?

Author: Puja K. Mehta, Olga Toleva, and Arshed A. Quyyumi
Subjects: medicine.medical_specialty, business.industry, Microcirculation, Heart, Coronary microcirculation, Coronary Vessels, Coronary Circulation, Internal medicine, Cardiology, Humans, Medicine, Cardiology and Cardiovascular Medicine, business, Vascular function
Published: 2021

44. Ambulatory and silent myocardial ischemia in women with coronary microvascular dysfunction: Results from the Cardiac Autonomic Nervous System study (CANS)

Author: Shilpa Sharma, Navid Darouian, Haider Aldiwani, Lian Li, C. Noel Bairey Merz, Margo Minissian, Michael D. Nelson, Janet Wei, Puja K. Mehta, Tina Torbati, Chrisandra Shufelt, and Rajasree Roy
Subjects: medicine.medical_specialty, Population, Myocardial Ischemia, Ischemia, Coronary Artery Disease, 030204 cardiovascular system & hematology, Autonomic Nervous System, Article, Coronary artery disease, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, ST segment, 030212 general & internal medicine, education, Depression (differential diagnoses), education.field_of_study, business.industry, medicine.disease, Autonomic nervous system, Blood pressure, Ambulatory, Electrocardiography, Ambulatory, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Background Up to two-thirds of patients with obstructive coronary artery disease (CAD) have silent ischemia (SI), which predicts an adverse prognosis and can be a treatment target in obstructive CAD. Over 50% of women with ischemia and no obstructive CAD have coronary microvascular dysfunction (CMD), which is associated with adverse cardiovascular outcomes. We aimed to investigate the prevalence of SI in CMD in order to consider it as a potential treatment target. Methods 36 women with CMD by coronary reactivity testing and 16 age matched reference subjects underwent 24-h 12-lead ambulatory ECG monitoring (Mortara Instruments) after anti-ischemia medication withdrawal. Ambulatory ECG recordings were reviewed by two-physician consensus masked to subject status for SI measured by evidence of ≥1 minute horizontal or downsloping ST segment depression ≥1.0 mm, measured 80 ms from the J point. Results Demographics, resting heart rate, and systolic blood pressure were similar between CMD and reference subjects. Thirty-nine percent of CMD women had a total of 26 SI episodes vs. 0 episodes in the reference group (p = 0.002). Among these women 13/14 (93%) had SI, and few episodes (3/26, 12%) were symptomatic. Mean HR at the onset of SI was 96 ± 13 bpm and increased to 117 ± 16 bpm during the ischemic episodes. 87% reported symptoms that were not associated with ST depressions. Conclusions Ambulatory ischemia is prevalent in women with CMD, with a majority being SI, while most reported symptoms were not accompanied by ambulatory ischemia. Clinical trials evaluating anti-ischemic medications should be considered in the CMD population.
Published: 2020

45. Yoga for Heart Failure

Author: Paula R. Seffens aka Pullen, Aneesha Thobani, William S. Seffens, Senait Asier, and Puja K. Mehta
Published: 2022

46. Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease

Author: Arnav Kumar, Sonu Gupta, Kreton Mavromatis, Puja K. Mehta, Olivia Y. Hung, Michael C. McDaniel, Habib Samady, Viola Vaccarino, Melroy D'Souza, Sonali Kumar, Parham Eshtehardi, John S. Douglas, Ahmed AlBadri, Jin-Sin Koh, Joo Myung Lee, Arshed A. Quyyumi, and Rani Rabah
Subjects: Male, Coronary angiography, medicine.medical_specialty, Coronary Artery Disease, Fractional flow reserve, 030204 cardiovascular system & hematology, Coronary Angiography, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Coronary Circulation, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Endothelial dysfunction, business.industry, Unstable angina, Microcirculation, Coronary flow reserve, General Medicine, Blood flow, medicine.disease, Coronary Vessels, Fractional Flow Reserve, Myocardial, Treatment Outcome, medicine.anatomical_structure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Artery
Abstract: BACKGROUND Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. METHODS 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4 M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR
Published: 2020

47. Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease

Author: Jonathon A. Nye, Paolo Raggi, Zakaria Almuwaqqat, Kasra Moazzami, Margarethe Goetz, Matthew T. Wittbrodt, Amit J. Shah, J. Douglas Bremner, Muhammad Hammadah, Ernest V. Garcia, Viola Vaccarino, Oleksiy Levantsevych, Brad D. Pearce, Puja K. Mehta, Yan V. Sun, Arshed A. Quyyumi, and Bruno B Lima
Subjects: Male, medicine.medical_specialty, Emotions, Myocardial Infarction, Prefrontal Cortex, Neuroimaging, Comorbidity, Coronary Artery Disease, Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Physiology (medical), Internal medicine, Mental stress, Heart rate, Myocardial Revascularization, medicine, Humans, Speech, Psychological stress, cardiovascular diseases, Angina, Unstable, Risk factor, Prefrontal cortex, Aged, Heart Failure, Inflammation, Interleukin-6, business.industry, Default Mode Network, Middle Aged, Prognosis, medicine.disease, Hospitalization, Heart Disease Risk Factors, Positron-Emission Tomography, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Mathematics, Stress, Psychological, 030217 neurology & neurosurgery, Mace
Abstract: Background:Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE.Methods:Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization.Results:We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08–1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (P=0.03).Conclusions:Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.
Published: 2020

48. Summary of Updated Recommendations for Primary Prevention of Cardiovascular Disease in Women

Author: Margo Minissian, Leslie Cho, Islam Y. Elgendy, Erin D. Michos, Kelly Epps, Viola Vaccarino, Melinda B. Davis, Carl J. Pepine, Puja K. Mehta, Kathryn J. Lindley, and Annabelle Santos Volgman
Subjects: medicine.medical_specialty, Aspirin, business.industry, medicine.medical_treatment, Atrial fibrillation, Guideline, Disease, 030204 cardiovascular system & hematology, medicine.disease, Gestational diabetes, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Medicine, 030212 general & internal medicine, Hormone therapy, Cardiology and Cardiovascular Medicine, business, Intensive care medicine, Psychosocial, medicine.drug
Abstract: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for women in the United States and worldwide. There has been no American College of Cardiology (ACC)/American Heart Association guideline update specifically for the prevention of CVD in women since 2011. Since then, the body of sex-specific data has grown, in addition to updated hypertension, cholesterol, diabetes, atrial fibrillation, and primary prevention guidelines. The ACC CVD in Women Committee undertook a review of the recent guidelines and major studies to summarize recommendations pertinent to women. In this update, the authors address special topics, particularly the risk factors and treatments that have led to some controversies and confusion. Specifically, sex-related risk factors, hypertension, diabetes, hyperlipidemia, anticoagulation for atrial fibrillation, use of aspirin, perimenopausal hormone therapy, and psychosocial issues are highlighted.
Published: 2020

49. Sex differences in non-obstructive coronary artery disease

Author: Jennifer A. Tremmel, Tara Sedlak, Angela H.E.M. Maas, Puja K. Mehta, Waddah Malas, Suzette E. Elias-Smale, and Nida Waheed
Subjects: Male, medicine.medical_specialty, Physiology, Adverse outcomes, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Inflammation, Coronary Artery Disease, 030204 cardiovascular system & hematology, Risk Assessment, Angina, Coronary artery disease, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Coronary Circulation, Physiology (medical), Internal medicine, medicine, Humans, 030212 general & internal medicine, Endothelial dysfunction, Sex Characteristics, Vasomotor, business.industry, Microcirculation, Health Status Disparities, Prognosis, medicine.disease, Coronary Vessels, Pathophysiology, Microvessels, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Sex characteristics
Abstract: Contains fulltext : 220971.pdf (Publisher’s version ) (Closed access) Ischaemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared with men, symptomatic women who are suspected of having myocardial ischaemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic, and neuroendocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.
Published: 2020

50. Pain in Rheumatoid Arthritis: Could JAK Inhibition be the Answer?

Author: Puja K. Mehta and Peter C. Taylor
Subjects: rheumatoid arthritis, lcsh:Diseases of the musculoskeletal system, business.industry, jak-stat, JAK-STAT signaling pathway, Review, medicine.disease, Rheumatology, Rheumatoid arthritis, Immunology, Medicine, pain, lcsh:RC925-935, business, jak inhibition
Abstract: Rheumatoid arthritis (RA) is an archetypal chronic, autoimmune inflammatory polyarthritis, which is characterized by peripheral joint pain, stiffness, and swelling. There have been considerable advances in management of RA, which has been revolutionized by the early and intensive use of immunotherapies. Despite these advances, pain is one of the largest unmet needs. Pain is multidimensional, defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”1. Patients with RA cite pain as their most important health priority2. Pain has wide biopsychosocial implication and can increase work-disability and health-care utilization3. Prognosis of pain in RA is often poor, even when inflammation is optimally controlled, i.e. ‘remaining pain’4. Better understanding of the characteristics, mechanisms and perception of pain, is critical in determining the most appropriate treatment approach. Escalation or switching of immunotherapies in patients with non-inflammatory pain, may be ineffective and unnecessarily risk loss of control of inflammation, as well as exposing patients to treatment-related adverse events. Furthermore, better understanding of non-inflammatory pain mechanisms may enable the development of targeted treatment strategies for specific subgroups of patients. The pain experience in RA is multifactorial, resulting from a complex interaction between genetics, psychology, comorbidities, joint pathology and alterations in both peripheral and central pain processing5. Diagnosing, measuring and appropriately managing pain in RA is very challenging. There is accumulating evidence to suggest that targeting the Janus kinase/signal transducer and activator of the transcription (JAK-STAT) pathway, may improve pain outcomes in RA. Here we describe the impact, mechanisms and difficulties associated with measuring pain in RA and emerging role of JAK inhibition.
Published: 2020

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