Faculty Bibliography

BACKGROUND: . Unique identifier: NCT00798122

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.

BACKGROUND:Women with chronic coronary disease have more frequent angina and worse health status than men, despite having less coronary artery disease (CAD). We examined whether perceived stress and depressive symptoms mediate sex differences in angina, and whether this relationship differs in the setting of obstructive CAD or ischemia with no obstructive coronary artery disease (INOCA). METHODS:We analyzed the association between sex, stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-8) on angina-related health status (Seattle Angina Questionnaire [SAQ]) at enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial and CIAO-ISCHEMIA (Changes in Ischemia and Angina Over 1 Year Among ISCHEMIA Trial Screen Failures With No Obstructive CAD on Coronary CT [Computed Tomography] Angiography) ancillary study. RESULTS:=0.012). Higher stress and depressive symptoms were associated with worse angina in both cohorts. Female sex, Perceived Stress Scale-4 score, and Patient Health Questionnaire-8 score were each independently associated with lower SAQ summary score, but CAD versus INOCA cohort was not. There was no interaction between sex and stress (-0.39 [95% CI, -1.01 to 0.23]) or sex and depression (-0.00 [95% CI, -0.53 to 0.53]) on SAQ summary score. CONCLUSIONS:High stress and depressive symptoms were independently associated with worse angina and poorer health status, without interaction with sex with or without obstructive CAD. Factors other than stress or depression contribute to worse health status in women with obstructive CAD or INOCA. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02347215, NCT01471522.

BACKGROUND/UNASSIGNED:The appropriate use criteria for revascularization of stable ischemic heart disease have not been evaluated using randomized data. Using data from the randomized ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; July 2012 to January 2018, 37 countries), the health status benefits of an invasive strategy over a conservative one were examined within appropriate use criteria scenarios. METHODS/UNASSIGNED:Among 1833 participants mapped to 36 appropriate use criteria scenarios, symptom status was assessed using the Seattle Angina Questionnaire-7 at 1 year for each scenario and for each of the 6 patient characteristics used to define the scenarios. Coronary anatomy and SYNTAX(Synergy between percutaneous coronary intervention with Taxus and cardiac surgery) scores were measured using coronary computed tomography angiography. Treatment effects are expressed as an odds ratio for a better health status outcome with an invasive versus conservative treatment strategy using Bayesian hierarchical proportional odds models. Differences in the primary clinical outcome were similarly examined. RESULTS/UNASSIGNED:The mean age was 63 years, 81% were male, and 71% were White. Diabetes was present in 28% and multivessel disease in 51%. Most clinical scenarios favored invasive for better 1-year health status. The benefit of an invasive strategy on Seattle Angina Questionnaire angina frequency scores was reduced for asymptomatic patients (odds ratio [95% credible interval], 1.16 [0.66-1.71] versus 2.26 [1.75-2.80]), as well as for those on no antianginal medications. Diabetes, number of diseased vessels, proximal left anterior descending coronary artery location, and SYNTAX score did not effectively identify patients with better health status after invasive treatment, and minimal differences in clinical events were observed. CONCLUSIONS/UNASSIGNED:Applying the randomization scheme from the ISCHEMIA trial to appropriate clinical scenarios revealed baseline symptoms and antianginal therapy to be the primary drivers of health status benefits from invasive management. Consideration should be given to reducing the patient characteristics collected to generate appropriateness ratings to improve the feasibility of future data collection. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

BACKGROUND/UNASSIGNED:Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. OBJECTIVES/UNASSIGNED:This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. METHODS/UNASSIGNED:Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. RESULTS/UNASSIGNED: = 0.036). CONCLUSIONS/UNASSIGNED:MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

BACKGROUND:Chronic coronary syndromes (CCS) occur commonly in the absence of flow-limiting epicardial coronary stenoses. Ischemia or angina with no obstructive coronary arteries (INOCA/ANOCA) may be caused by coronary microvascular disease, coronary artery spasm, myocardial bridging, diffuse atherosclerosis, or a combination of disorders. METHODS & RESULTS/RESULTS:We highlight the new recommendations in the 2024 European Society of Cardiology (ESC) guidelines on CCS relevant to the diagnosis and management of INOCA/ANOCA. The guidelines place a new emphasis on consideration of INOCA/ANOCA early during cardiovascular risk stratification and the initial diagnostic workup for chest pain. There is a new class I recommendation for the availability of invasive coronary function testing (CFT) at the time of initial coronary angiography, when mechanisms of chest pain are uncertain after non-invasive testing, and in patients with established INOCA/ANOCA who have persistent symptoms and poor quality of life despite medical therapy. Once underlying disorders have been identified based on the results of invasive CFT, the ESC guidelines emphasize a patient-centered, mechanism-based approach to medical treatment of INOCA/ANOCA to improve symptoms and quality of life. CONCLUSIONS:The 2024 ESC CCS guidelines provide a new vision for the diagnosis and management of ANOCA/INOCA, with an expanded role for invasive CFT and targeted medical therapy to improve symptoms and quality of life in patients with angina.

BACKGROUND:In myocardial infarction with nonobstructive coronary arteries (MINOCA), there are limited patient-level data on outcomes by sex and race. OBJECTIVE:The aim of this study was to assess baseline demographics and 3-year outcomes by sex and race for MINOCA patients. METHODS:Patients admitted to a single center with acute myocardial infarction (MI) between 1 January 2012 and 31 December 2018, were identified by chart and angiographic review. The primary outcome was nonfatal MI with secondary outcomes including nonfatal cerebrovascular accident (CVA), chest pain readmission, and repeat coronary angiography. RESULTS:During the study period, 304 patients were admitted with MINOCA. The cohort was predominantly female (66.4%), and women were significantly older (64.6 vs. 59.2). One-sixth of the total population were Black patients, and nearly half of Black patients (47.2%) were male. Prior CVA (19.7%) and comorbid anxiety, depression, or post-traumatic stress disorder (41.1%) were common. Rates of nonfatal MI were 6.3% without difference by sex or race. For secondary outcomes, rates of CVA were 1.7%, chest pain readmission was 22.4%, and repeat angiography was 8.9%. Men were significantly more likely to have repeat angiography (13.7 vs. 6.4%), and Black patients were more likely to be readmitted for angina (34.0 vs. 19.1%). Over one-quarter of patients underwent repeat stress testing, with 8.9% ultimately undergoing repeat angiograms and low numbers (0.7%) undergoing revascularization. Men were more likely to be referred for a repeat angiogram (13.7 vs. 6.4%, P = 0.035). In multivariate analysis, Black race [odds ratio (OR), 2.31; 95% confidence interval (CI), 1.06-5.03] was associated with an increased risk of readmission for angina, while female sex was associated with decreased odds of repeat angiography (OR, 0.36; 95% CI, 0.14-0.90) and current smoking was associated with increased odds of repeat angiography (OR, 4.07; 95% CI, 1.02-16.29)] along with hyperlipidemia (OR, 4.65; 95% CI, 1.22-17.7). CONCLUSION/CONCLUSIONS:White women presented more frequently with MINOCA than White men, however, Black men are equally as affected as Black women. Rates of nonfatal MI were low without statistical differences by sex or race.

BACKGROUND/UNASSIGNED:The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography. METHODS/UNASSIGNED:Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index. RESULTS/UNASSIGNED:Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity. CONCLUSIONS/UNASSIGNED:Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

BACKGROUND:Whether revascularisation (REV) improves outcomes in patients with three-vessel coronary artery disease (3V-CAD) is uncertain. AIMS/OBJECTIVE:Our objective was to evaluate outcomes with REV (percutaneous coronary intervention [PCI] or coronary artery bypass graft surgery [CABG]) versus medical therapy in patients with 3V-CAD. METHODS:ISCHEMIA participants with 3V-CAD on coronary computed tomography angiography without prior CABG were included. Outcomes following initial invasive management (INV) with REV (PCI or CABG) versus initial conservative management (CON) with medical therapy alone were evaluated. Regression modelling was used to estimate the outcomes if all participants were to undergo prompt REV versus those assigned to CON. Outcomes were cardiovascular (CV) death/myocardial infarction (MI), death, CV death, and quality of life. Bayesian posterior probability for benefit (Pr [benefit]) for 1 percentage point lower 4-year rates with REV versus CON were evaluated. RESULTS:Among 1,236 participants with 3V-CAD (612 INV/624 CON), REV was associated with lower 4-year CV death/MI (adjusted 4-year difference: -4.4, 95% credible interval [CrI] -8.7 to -0.3 percentage points, Pr [benefit]=94.8%) when compared with CON, with similar results for PCI versus CON (-5.8, 95% CrI: -10.8 to -0.5 percentage points, Pr [benefit]=96.4%) and CABG versus CON (-3.7, 95% CrI: -8.8 to 1.5 percentage points, Pr [benefit]=84.7%). Adjusted 4-year REV versus CON differences were as follows: death -1.2 (95% CrI: -4.7 to 2.2) percentage points, CV death -2.3 (95% CrI: -5.5 to 0.8) percentage points, with similar results for PCI and for CABG. The Pr (benefit) for death with REV (PCI or CABG) versus CON was 49-63%. The adjusted 12-month Seattle Angina Questionnaire-7 summary score differences favoured REV: REV versus CON 4.6 (95% CrI: 2.7-6.4) percentage points; PCI versus CON 3.6 (95% CrI: 1.2-5.8) percentage points and CABG versus CON 4.3 (95% CrI: 1.5-6.9) percentage points with high Pr (benefit). CONCLUSIONS:In participants with 3V-CAD, REV (either PCI or CABG) was associated with a lower 4-year CV death/MI rate and improved quality of life, with similar results for PCI versus CON and CABG versus CON. The differences in all-cause mortality between REV and CON were small with wide confidence intervals. (ClinicalTrials.gov: NCT01471522).