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Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease

Reynolds HR; Srichai MB; Iqbal SN; Slater JN; Mancini GB; Feit F; Pena-Sing I; Axel L; Attubato MJ; Yatskar L; Kalhorn RT; Wood DA; Lobach IV; Hochman JS
BACKGROUND: . Unique identifier: NCT00798122
PMCID:3619391
PMID: 21900087
ISSN: 1524-4539
CID: 137093

ESC working group position paper on myocardial infarction with non-obstructive coronary arteries

Agewall, Stefan; Beltrame, John F; Reynolds, Harmony R; Niessner, Alexander; Rosano, Giuseppe; Caforio, Alida L P; De Caterina, Raffaele; Zimarino, Marco; Roffi, Marco; Kjeldsen, Keld; Atar, Dan; Kaski, Juan C; Sechtem, Udo; Tornvall, Per
PMID: 28158518
ISSN: 1522-9645
CID: 2435942

Autonomic Findings in Takotsubo Cardiomyopathy

Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio; Martinez, Jose; Katz, Stuart D; Tully, Lisa; Reynolds, Harmony R
Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow-mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.
PMID: 26743349
ISSN: 1879-1913
CID: 1901192

Cardiometabolic Comorbidity Burden and Circulating Biomarkers in Patients with Chronic Coronary Disease in the ISCHEMIA Trials

Hamo, Carine E; Liu, Richard; Wu, Wenbo; Anthopolos, Rebecca; Bangalore, Sripal; Held, Claes; Kullo, Ifitkhar; Mavromatis, Kreton; McManus, Bruce; Newby, L Kristin; Reynolds, Harmony R; Ruggles, Kelly V; Wallentin, Lars; Maron, David J; Hochman, Judith S; Newman, Jonathan D; Berger, Jeffrey S; ,
Cardiometabolic comorbidities, diabetes (DM), hypertension (HTN), and obesity, contribute to cardiovascular disease (CVD). Circulating biomarkers facilitate prognostication for patients with CVD. We explored the relationship between cardiometabolic comorbidity burden in patients with chronic coronary disease (CCD) and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the ISCHEMIA Trials biorepository with plasma biomarkers (NT-proBNP, hs-cTnT, hs-CRP, IL-6, sCD40L, and GDF-15) and clinical risk factors [hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI)] at baseline. We defined cardiometabolic comorbidities as DM, HTN, and obesity at baseline. Comorbidity burden characterized by number and severity of comorbidities. Controlled comorbidities were defined as HbA1c <7% for those with DM, SBP <130 mmHg for those with HTN and BMI <30 kg/m2. Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mmHg, and BMI ≥35 kg/m2. We performed linear regression analyses to examine the association between comorbidity burden and log-transformed biomarker levels adjusting for age, sex, eGFR controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 individuals (mean age 66, 19% female, 84% white) were included in this analysis. Self-reported Black race, current smokers, history of MI and HF had greater cardiometabolic comorbidity burden. The presence of ≥ 1 severely uncontrolled comorbidity was associated with significantly higher baseline levels of hs-cTnT, hs-CRP, IL-6, and GDF-15 compared to participants with no comorbidities. In conclusion, increasing cardiometabolic comorbidity burden in patients with CCD is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.
PMID: 38844195
ISSN: 1879-1913
CID: 5665722

Author Correction: Optical coherence tomography in coronary atherosclerosis assessment and intervention

Araki, Makoto; Park, Seung-Jung; Dauerman, Harold L; Uemura, Shiro; Kim, Jung-Sun; Di Mario, Carlo; Johnson, Thomas W; Guagliumi, Giulio; Kastrati, Adnan; Joner, Michael; Holm, Niels Ramsing; Alfonso, Fernando; Wijns, William; Adriaenssens, Tom; Nef, Holger; Rioufol, Gilles; Amabile, Nicolas; Souteyrand, Geraud; Meneveau, Nicolas; Gerbaud, Edouard; Opolski, Maksymilian P; Gonzalo, Nieves; Tearney, Guillermo J; Bouma, Brett; Aguirre, Aaron D; Mintz, Gary S; Stone, Gregg W; Bourantas, Christos V; Räber, Lorenz; Gili, Sebastiano; Mizuno, Kyoichi; Kimura, Shigeki; Shinke, Toshiro; Hong, Myeong-Ki; Jang, Yangsoo; Cho, Jin Man; Yan, Bryan P; Porto, Italo; Niccoli, Giampaolo; Montone, Rocco A; Thondapu, Vikas; Papafaklis, Michail I; Michalis, Lampros K; Reynolds, Harmony; Saw, Jacqueline; Libby, Peter; Weisz, Giora; Iannaccone, Mario; Gori, Tommaso; Toutouzas, Konstantinos; Yonetsu, Taishi; Minami, Yoshiyasu; Takano, Masamichi; Raffel, O Christopher; Kurihara, Osamu; Soeda, Tsunenari; Sugiyama, Tomoyo; Kim, Hyung Oh; Lee, Tetsumin; Higuma, Takumi; Nakajima, Akihiro; Yamamoto, Erika; Bryniarski, Krzysztof L; Di Vito, Luca; Vergallo, Rocco; Fracassi, Francesco; Russo, Michele; Seegers, Lena M; McNulty, Iris; Park, Sangjoon; Feldman, Marc; Escaned, Javier; Prati, Francesco; Arbustini, Eloisa; Pinto, Fausto J; Waksman, Ron; Garcia-Garcia, Hector M; Maehara, Akiko; Ali, Ziad; Finn, Aloke V; Virmani, Renu; Kini, Annapoorna S; Daemen, Joost; Kume, Teruyoshi; Hibi, Kiyoshi; Tanaka, Atsushi; Akasaka, Takashi; Kubo, Takashi; Yasuda, Satoshi; Croce, Kevin; Granada, Juan F; Lerman, Amir; Prasad, Abhiram; Regar, Evelyn; Saito, Yoshihiko; Sankardas, Mullasari Ajit; Subban, Vijayakumar; Weissman, Neil J; Chen, Yundai; Yu, Bo; Nicholls, Stephen J; Barlis, Peter; West, Nick E J; Arbab-Zadeh, Armin; Ye, Jong Chul; Dijkstra, Jouke; Lee, Hang; Narula, Jagat; Crea, Filippo; Nakamura, Sunao; Kakuta, Tsunekazu; Fujimoto, James; Fuster, Valentin; Jang, Ik-Kyung
PMID: 38110566
ISSN: 1759-5010
CID: 5611732

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction

Mayer, Michael; Allan, Tess; Harkin, Kenneth L; Loftspring, Ethan; Saffari, Seyed E; Reynolds, Harmony R; Paul, Jonathan; Kalathiya, Rohan; Shah, Atman P; Nathan, Sandeep; McCarthy, Mary C; Smilowitz, Nathaniel R; Miner, Steven E S; Blair, John
BACKGROUND:Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES/OBJECTIVE:The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS:Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS:Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS:Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.
PMCID:11098671
PMID: 38599696
ISSN: 1876-7605
CID: 5655752

Coronary Microvascular Dysfunction Is Associated With a Proinflammatory Circulating Transcriptome in Patients With Nonobstructive Coronary Arteries

Smilowitz, Nathaniel R; Schlamp, Florencia; Hausvater, Anaïs; Joa, Amanda; Serrano-Gomez, Claudia; Farid, Ayman; Hochman, Judith S; Barrett, Tessa; Reynolds, Harmony R; Berger, Jeffrey S
PMID: 38299358
ISSN: 1524-4636
CID: 5627252

Therapeutic Heparin in non-ICU patients Hospitalized for COVID-19 in the ACTIV-4a Trial: Effect on 3 Month Symptoms and Quality of Life

Greenstein, Yonatan Y; Hubel, Kinsley; Froess, Joshua; Wisniewski, Stephen R; Venugopal, Vidya; Lai, Yu-Hsuan; Berger, Jeff S; Chang, Steven Y; Colovos, Christos; Shah, Faraaz; Kornblith, Lucy Z; Lawler, Patrick R; Gaddh, Manila; Guerrero, Raquel Morillo; Nkemdirim, William; Lopes, Renato D; Reynolds, Harmony R; Amigo, Jose Seijas; Wahid, Lana; Zahra, Ajani; Goligher, Ewan C; Zarychanski, Ryan; Leifer, Eric; Huang, David T; Neal, Matthew D; Hochman, Judith S; Cushman, Mary; Gong, Michelle N
BACKGROUND:Therapeutic-dose heparin decreased days requiring organ support in non-critically ill patients hospitalized for COVID-19 but its impact on persistent symptoms or quality of life (QoL) is unclear. RESEARCH QUESTION/OBJECTIVE:In the ACTIV-4a trial, was randomization of patients hospitalized for COVID-19 illness to therapeutic-dose vs. prophylactic heparin associated with less symptoms and better QoL at 90-days? STUDY DESIGN AND METHODS/METHODS:This was an open-label randomized controlled trial at 34 hospitals in the US and Spain. 727 non-critically ill patients hospitalized for COVID-19 from September 2020 to June 2021 were randomized to therapeutic-dose vs. prophylactic heparin. Only patients with 90-day data on symptoms and QoL were analyzed. We ascertained symptoms and QoL by EQ-5D-5L at 90-day follow-up in a pre-planned analysis for the ACTIV-4a trial. Individual domains assessed by the EQ-5D-5L were mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Univariate and multivariate analysis were performed. RESULTS:Among 571 patients, 288 (50.4%) reported at least one symptom. In 410 patients, 148 (36.1%) reported moderate to severe impairment in one or more domains of EQ-5D-5L. Presence of 90-day symptoms were associated with moderate-severe impairment in the EQ-5D-5L domains of mobility (adjusted odds ratio (aOR) 2.37, 95% CI 1.22-4.59), usual activity (aOR 3.66, 95% CI 1.75-7.65), pain (aOR 2.43, 95% CI 1.43-4.12), and anxiety (aOR 4.32, 95% CI 2.06-9.02), compared to patients reporting no symptoms There were no differences in symptoms or the overall EQ-5D-5L index score between treatment groups. Therapeutic-dose heparin was associated with less moderate-severe impairment in all physical functioning domains (mobility, self-care, usual activities) but was independently significant only in the self-care domain (aOR 0.32, CI 0.11-0.96). INTERPRETATION/CONCLUSIONS:In a randomized controlled trial of hospitalized non-critically ill patients with COVID-19, therapeutic-dose heparin was associated with less severe impairment in the self-care domain of EQ-5D-5L. However, this type of impairment was uncommon, affecting 23 individuals. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT04505774.
PMID: 37979717
ISSN: 1931-3543
CID: 5608182

Impact of Visit Volume on the Effectiveness of Electronic Tools to Improve Heart Failure Care

Mukhopadhyay, Amrita; Reynolds, Harmony R; King, William C; Phillips, Lawrence M; Nagler, Arielle R; Szerencsy, Adam; Saxena, Archana; Klapheke, Nathan; Katz, Stuart D; Horwitz, Leora I; Blecker, Saul
BACKGROUND:Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. OBJECTIVES/OBJECTIVE:This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. METHODS:This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. RESULTS:Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non-high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non-high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). CONCLUSIONS:An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920).
PMID: 38043045
ISSN: 2213-1787
CID: 5597482

Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial

Reynolds, Harmony R; Cyr, Derek D; Merz, C Noel Bairey; Shaw, Leslee J; Chaitman, Bernard R; Boden, William E; Alexander, Karen P; Rosenberg, Yves D; Bangalore, Sripal; Stone, Gregg W; Held, Claes; Spertus, John; Goetschalckx, Kaatje; Bockeria, Olga; Newman, Jonathan D; Berger, Jeffrey S; Elghamaz, Ahmed; Lopes, Renato D; Min, James K; Berman, Daniel S; Picard, Michael H; Kwong, Raymond Y; Harrington, Robert A; Thomas, Boban; O'Brien, Sean M; Maron, David J; Hochman, Judith S; ,
BACKGROUND:Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. METHODS AND RESULTS/RESULTS:=0.49), with no significant sex-by-treatment-group interactions. CONCLUSIONS:Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. REGISTRATION/BACKGROUND:URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.
PMCID:10944079
PMID: 38410945
ISSN: 2047-9980
CID: 5645612