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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
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

Cluster-Randomized Trial Comparing Ambulatory Decision Support Tools to Improve Heart Failure Care

Mukhopadhyay, Amrita; Reynolds, Harmony R; Phillips, Lawrence M; Nagler, Arielle R; King, William C; Szerencsy, Adam; Saxena, Archana; Aminian, Rod; Klapheke, Nathan; Horwitz, Leora I; Katz, Stuart D; Blecker, Saul
BACKGROUND:Mineralocorticoid receptor antagonists (MRA) are under-prescribed for patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE:To compare effectiveness of two automated, electronic health record (EHR)-embedded tools vs. usual care on MRA prescribing in eligible patients with HFrEF. METHODS:BETTER CARE-HF (Building Electronic Tools To Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) was a three-arm, pragmatic, cluster-randomized trial comparing the effectiveness of an alert during individual patient encounters vs. a message about multiple patients between encounters vs. usual care on MRA prescribing. We included adult patients with HFrEF, no active MRA prescription, no contraindication to MRA, and an outpatient cardiologist in a large health system. Patients were cluster-randomized by cardiologist (60 per arm). RESULTS:The study included 2,211 patients (alert: 755, message: 812, usual care [control]: 644), with average age 72.2 years, average EF 33%, who were predominantly male (71.4%) and White (68.9%). New MRA prescribing occurred in 29.6% of patients in the alert arm, 15.6% in the message arm, and 11.7% in the control arm. The alert more than doubled MRA prescribing compared to control (RR: 2.53, 95% CI: 1.77-3.62, p<0.0001), and improved MRA prescribing compared to the message (RR: 1.67, 95% CI: 1.21-2.29, p=0.002). The number of patients with alert needed to result in an additional MRA prescription was 5.6. CONCLUSIONS:An automated, patient-specific, EHR-embedded alert increased MRA prescribing compared to both a message and usual care. Our findings highlight the potential for EHR-embedded tools to substantially increase prescription of life-saving therapies for HFrEF. (NCT05275920).
PMID: 36882134
ISSN: 1558-3597
CID: 5430312

Repetitive catamenial myocardial infarction due to coronary artery spasm: a case report [Case Report]

Talmor, Nina; Gurin, Michael; Smilowitz, Nathaniel; Gossett, Dana; Eisner, Bruria; Pleasure, Mitchell; Reynolds, Harmony R
BACKGROUND/UNASSIGNED:Coronary artery spasm is an established mechanism of myocardial infarction with non-obstructive coronary arteries (MINOCA). Various mechanisms have been proposed, ranging from vascular smooth muscle hyperreactivity to endothelial dysfunction, to autonomic nervous system dysregulation. CASE SUMMARY/UNASSIGNED:We report a case of a 37-year-old woman who presented with recurrent non-ST elevation myocardial infarction (NSTEMI), coinciding with her menstrual periods. Intracoronary acetylcholine provocation testing resulted in coronary spasm in the left anterior descending artery (LAD) that was relieved with nitroglycerine. Initiating calcium channel blockade and suppressing cyclical variation in sex hormones resulted in improvement of her symptoms and cessation of monthly NSTEMI events due to coronary spasm. DISCUSSION/UNASSIGNED:Initiating calcium channel blockade and suppressing cyclical variation in sex hormones resulted in improvement of her symptoms and cessation of monthly NSTEMI events due to coronary spasm. Catamenial coronary artery spasm is a rare, but clinically important, presentation of myocardial infarction with non-obstructive coronary arteries (MINOCA).
PMID: 36793935
ISSN: 2514-2119
CID: 5439902

Myocardial Infarction with Nonobstructive Coronary Arteries

Reynolds, H R; Smilowitz, N R
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an important subtype of myocardial infarction (MI) that occurs in approximately 6-8% of patients with spontaneous MI who are referred for coronary angiography. MINOCA disproportionately affects women, but men are also affected. Pathogenesis is more variable than in MI with obstructive coronary artery disease (MI-CAD). Dominant mechanisms include atherosclerosis, thrombosis, and coronary artery spasm. Management of MINOCA varies based on the underlying mechanism of infarction. Therefore, systematic approaches to diagnosis are recommended. The combination of invasive coronary angiography, multivessel intracoronary imaging, provocative testing for coronary spasm, and cardiac magnetic resonance imaging provides the greatest diagnostic yield. Current clinical practice guidelines for the secondary prevention of MI are based largely on data from patients with MI-CAD. Thus, optimal medications after MINOCA are uncertain. Clinical trials focused on the treatment of patients with MINOCA are urgently needed to define optimal care. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see for revised estimates.
PMID: 36179347
ISSN: 1545-326x
CID: 5334662

Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial

Sidhu, Mandeep S; Alexander, Karen P; Huang, Zhen; Mathew, Roy O; Newman, Jonathan D; O'Brien, Sean M; Pellikka, Patricia A; Lyubarova, Radmila; Bockeria, Olga; Briguori, Carlo; Kretov, Evgeny L; Mazurek, Tomasz; Orso, Francesco; Roik, Marek F; Sajeev, Chakkanalil; Shutov, Evgeny V; Rockhold, Frank W; Borrego, David; Balter, Stephen; Stone, Gregg W; Chaitman, Bernard R; Goodman, Shaun G; Fleg, Jerome L; Reynolds, Harmony R; Maron, David J; Hochman, Judith S; Bangalore, Sripal
BACKGROUND:In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). OBJECTIVES/OBJECTIVE:This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death. METHODS:Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified. RESULTS:A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy. CONCLUSIONS:In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360).
PMID: 36697158
ISSN: 1876-7605
CID: 5410812

Design and pilot implementation for the BETTER CARE-HF trial: A pragmatic cluster-randomized controlled trial comparing two targeted approaches to ambulatory clinical decision support for cardiologists

Mukhopadhyay, Amrita; Reynolds, Harmony R; Xia, Yuhe; Phillips, Lawrence M; Aminian, Rod; Diah, Ruth-Ann; Nagler, Arielle R; Szerencsy, Adam; Saxena, Archana; Horwitz, Leora I; Katz, Stuart D; Blecker, Saul
BACKGROUND:Beart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown. METHODS AND RESULTS/RESULTS:We developed two targeted CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: (1) an alert that notifies cardiologists at the time of patient visit, and (2) an automated electronic message that allows for review between visits. We designed these tools using an established CDS framework and findings from semistructured interviews with cardiologists. We then pilot tested both CDS tools (n = 596 patients) and further enhanced them based on additional semistructured interviews (n = 11 cardiologists). The message was modified to reduce the number of patients listed, include future visits, and list date of next visit. The alert was modified to improve noticeability, reduce extraneous information on guidelines, and include key information on contraindications. CONCLUSIONS:The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of the alert vs. the automated message vs. usual care on the primary outcome of MRA prescribing. To our knowledge, no study has directly compared the efficacy of these two different types of electronic CDS interventions. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. (Trial registration: NCT05275920).
PMID: 36640860
ISSN: 1097-6744
CID: 5403312

Survival After Invasive or Conservative Management of Stable Coronary Disease

Hochman, Judith S; Anthopolos, Rebecca; Reynolds, Harmony R; Bangalore, Sripal; Xu, Yifan; O'Brien, Sean M; Mavromichalis, Stavroula; Chang, Michelle; Contreras, Aira; Rosenberg, Yves; Kirby, Ruth; Bhargava, Balram; Senior, Roxy; Banfield, Ann; Goodman, Shaun G; Lopes, Renato D; Pracon, Radoslaw; López-Sendón, José; Maggioni, Aldo Pietro; Newman, Jonathan D; Berger, Jeffrey S; Sidhu, Mandeep S; White, Harvey D; Troxel, Andrea B; Harrington, Robert A; Boden, William E; Stone, Gregg W; Mark, Daniel B; Spertus, John A; Maron, David J
PMID: 36335918
ISSN: 1524-4539
CID: 5356892

Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial

Reynolds, Harmony R; Diaz, Ariel; Cyr, Derek D; Shaw, Leslee J; Mancini, G B John; Leipsic, Jonathon; Budoff, Matthew J; Min, James K; Hague, Cameron J; Berman, Daniel S; Chaitman, Bernard R; Picard, Michael H; Hayes, Sean W; Scherrer-Crosbie, Marielle; Kwong, Raymond Y; Lopes, Renato D; Senior, Roxy; Dwivedi, Sudhanshu K; Miller, Todd D; Chow, Benjamin J W; de Silva, Ramesh; Stone, Gregg W; Boden, William E; Bangalore, Sripal; O'Brien, Sean M; Hochman, Judith S; Maron, David J
BACKGROUND:Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES/OBJECTIVE:The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS:Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS:Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, women female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS:Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).
PMID: 36115814
ISSN: 1876-7591
CID: 5336642