IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. METHODS: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. RESULTS: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P=0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P=0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P=0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. CONCLUSIONS: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Spontaneous Coronary Artery Dissection (SCAD) from an Interventionalist Perspective.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS), particularly among women < 50 years of age. Here, we aim to review the pathogenesis of SCAD, discuss SCAD as an initial manifestation of systemic arterial disease, and highlight invasive strategies as well as unique challenges in the care of women with SCAD. RECENT FINDINGS: A paradigm shift has occurred in the care of SCAD patients in the past decade as recommendations for conservative management have become widespread. Invasive interventions are reserved for patients with hemodynamic compromise or active ischemia due to increased periprocedural complications and failure rates. Certain patient populations have been identified for larger territory infarcts and proximal disease including patients with known connective tissue disease, premenopausal women, and patients with pregnancy-associated SCAD (P-SCAD). Current recommended management of SCAD is conservative. Despite a growing awareness of SCAD and its known association with systemic arteriopathies in women, evidence-based data remains scarce. Future studies focused on identifying genetic factors, optimal medical therapy after SCAD, and techniques to minimize interventional complications are needed.

Early Effects of the COVID-19 Pandemic on Patients in a Virtual Multicenter Spontaneous Coronary Artery Dissection (SCAD) Registry.

Background: The COVID-19 pandemic effects among patients with a history of spontaneous coronary artery dissection (SCAD), a cause of acute coronary syndrome associated with emotional and physical stress, are unknown. Methods: For this cross-sectional cohort study, participants of the Mayo Clinic "Virtual" Multicenter SCAD Registry were surveyed about the COVID-19 pandemic. Results: Among 1352 participants, 727 (53.8%) completed surveys between June 2, 2021 and September 29, 2021. The majority of respondents (96.7%) were female, with a mean age of 54.9 ± 9.4 years. At the time of completing the survey, which was early in the pandemic, 91 respondents (12.6%) reported having prior COVID-19 symptoms, with < 1% experiencing hospitalization (n = 4) or cardiac complications (n = 6). A total of 14% had ≥ moderate anxiety symptoms, per the General Anxiety Disorder-7 item survey, and 11.8% had ≥ moderate depressive symptoms, per the Patient Health Questionnaire-9 item. Higher stress scores on the Likert scale were correlated with pandemic-related reduction in work hours and/or pay and/or unemployment (P = 0.013), remote work and/or change of job (P < 0.001), and loss of insurance and/or medical coverage (P = 0.025). A higher anxiety level, as measured on the Likert scale, was correlated with pandemic-related remote work and/or change of job (P = 0.007) and loss of insurance and/or medical coverage (P = 0.008). Since the start of the pandemic, 54% of respondents reported having at least monthly chest pain. Chest pain and COVID symptoms were each associated with higher scores on the General Anxiety Disorder-7 item survey and the Patient Health Questionnaire-9 item. Conclusions: Early in the pandemic, COVID-19 symptoms, hospitalization, and cardiac complications were uncommon among SCAD patients. The burden of anxiety and depressive symptoms was minimal to mild, similar to that in prior reports. Likert-scale measures of stress and anxiety were higher among persons with work and/or pay reduction and/or unemployment, remote work and/or change of job, and loss of insurance and/or medical coverage. Over half of respondents reported experiencing chest pain, which was correlated with depressive and anxiety symptoms, highlighting an overarching clinical need.

Contexte: On ne connaît pas les effets de la pandémie de COVID-19 sur les personnes ayant des antécédents de dissection spontanée de l'artère coronaire (DSAC), une cause du syndrome coronarien aigu qui est une source de stress physique et émotionnel. Méthodologie: Pour les besoins de cette étude de cohorte transversale, les participants au registre « virtuel ¼ multicentrique sur la DSAC de la clinique Mayo ont été interrogés dans le cadre d'une enquête sur la pandémie de COVID-19. Résultats: Parmi les 1 352 participants au registre, 727 (53,8 %) ont répondu à l'enquête entre le 2 juin et le 29 septembre 2021. La majorité des répondants (96,7 %) étaient des femmes, et l'âge moyen était de 54,9 ± 9,4 ans. Au moment de l'enquête, réalisée au début de la pandémie, 91 répondants (12,6 %) avaient indiqué avoir déjà présenté des symptômes de COVID-19, et < 1 % avaient été hospitalisés (n = 4) ou avaient présenté des complications cardiaques (n = 6). Au total, 14 % des participants présentaient des symptômes d'anxiété à tout le moins modérés d'après le questionnaire GAD-7 (General Anxiety Disorder-7 item) et 11,8 %, des symptômes dépressifs à tout le moins modérés d'après le questionnaire PHQ-9 (Patient Health Questionnaire-9 item). Une corrélation a été établie entre un score de stress plus élevé sur une échelle de Likert et une réduction des heures de travail et/ou du salaire, une période de chômage (p = 0,013), le télétravail et/ou un changement d'emploi (p < 0,001) et la perte de l'assurance et/ou de la couverture médicale (p = 0,025) en lien avec la pandémie. Une corrélation a également été établie entre un niveau d'anxiété plus élevé mesuré sur une échelle de Likert et le télétravail et/ou un changement d'emploi (p = 0,007) et la perte de l'assurance et/ou de la couverture médicale (p = 0,008) en lien avec la pandémie. Depuis le début de la pandémie, 54 % des répondants ont indiqué ressentir une douleur thoracique au moins une fois par mois. La douleur thoracique et les symptômes de la COVID-19 ont par ailleurs été associés à des scores plus élevés aux questionnaires GAD-7 et PHQ-9. Conclusions: Au début de la pandémie, les symptômes de la COVID-19, les hospitalisations et les complications cardiaques n'étaient pas fréquents chez les patients présentant une DSAC. Le fardeau des symptômes anxieux et dépressifs allait de minime à léger, comme en faisaient état les rapports précédents. L'anxiété et le stress mesurés sur une échelle de Likert ont été plus élevés chez les personnes ayant connu une réduction des heures de travail et/ou du salaire ou une période de chômage, ayant dû recourir au télétravail et/ou changer d'emploi, ou ayant perdu leur assurance et/ou couverture médicale. Plus de la moitié des répondants ont indiqué ressentir une douleur thoracique, laquelle a été mise en corrélation avec les symptômes d'anxiété et de dépression, ce qui souligne l'existence d'un besoin clinique important.

Coronary Artery Tortuosity and Spontaneous Coronary Artery Dissection: Association With Echocardiography and Global Longitudinal Strain, Fibromuscular Dysplasia, and Outcomes.

BACKGROUND: The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed. METHODS: TCA was determined on coronary angiography performed during the diagnosis of SCAD, and cardiac structure and function were evaluated using prospective comprehensive echocardiography. RESULTS: Among 116 patients with SCAD, the mean age at echocardiography was 50.8 ± 8.8 years, a median of 10.9 months after SCAD. Sixty-two patients (53.4%) had FMD, 41 (35.3%) had histories of hypertension, and 17 (14.8%) were hypertensive during echocardiography. Most patients (n = 78 [69%]) had normal left ventricular geometry with normal median ejection fraction (61%; interquartile range, 56% to 64%) and normal global longitudinal strain (-22.2%; interquartile range, -24.0% to -19.9%). Fifteen patients (13.4%) had diastolic dysfunction that was associated with hypertension at the time of echocardiography. Patients with TCA (n = 96 [82.8%]) were older (mean age, 52.1 ± 8.0 vs 44.7 ± 9.9 years; P < .001) with a higher prevalence of FMD (59.4% vs 25%, P = .007) but a similar prevalence of hypertension (35% vs 35%, P > .99) compared with patients without TCA. Across the age range (31.5 to 66.9 years), each decade of age was associated with an approximately 0.89-unit increase in coronary tortuosity score (P < .0001). Echocardiographic parameters were not significantly different between the two groups. Median follow-up duration was 4.4 years (95% CI, 3.8 to 5.2 years). The Kaplan-Meier 3-year SCAD recurrence rate was 9.4% (95% CI, 3.7% to 14.8%). There were no deaths. CONCLUSIONS: The majority of patients with SCAD had normal or near normal echocardiographic results, including global longitudinal strain, with no differences according to TCA. However, patients with SCAD with TCA were older, with a higher prevalence of FMD.

Clinical features, management, and prognosis of spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized. METHODS AND RESULTS: A retrospective single-center cohort study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P<0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection. CONCLUSIONS: SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor.

Association of Spontaneous Coronary Artery Dissection With Atrial Arrhythmias.

The co-morbidities and long-term complications of spontaneous coronary artery dissection (SCAD) are incompletely understood. This study investigated the association of atrial arrhythmias (AA), defined as atrial fibrillation and atrial flutter, with SCAD in a patient registry and population-based cohort. This observational study was performed in 2 parts. The first was a retrospective study reviewing patients diagnosed with AA in the Mayo Clinic SCAD Registry. The second was a population-based, case-control study to assess AA in patients with SCAD compared with age- and gender-matched controls. Of 1,214 patients in the Mayo Clinic SCAD Registry, 45 patients (3.7%) with SCAD were identified with an AA. A total of 8 of those patients (17.8%) had a pre-SCAD AA; 20 (44.4%) had a peri-SCAD AA; and 17 (37.8%) had a post-SCAD AA. The univariate analysis did not reveal significant associations with traditional cardiovascular risk factors. In the population-based cohort, 5 patients with SCAD (4%) and 4 controls (1%) developed an AA before the date of SCAD for each patient (odds ratio 4.5, 95% confidence interval [CI] 1.05 to 19.0, p = 0.04). A total of 5 patients with SCAD (4%) and 3 controls (1%) developed an AA in the 10 years after SCAD (hazard ratio 6.3, 95% CI 1.2 to 32.8, p = 0.03). A subgroup of patients with SCAD experienced AA before and after SCAD. Patients with a history of SCAD were more likely to develop AA in the next 10 years than were age- and gender-matched healthy controls.

Prevention and management of contrast-induced acute kidney injury.

OPINION STATEMENT: Contrast-induced acute kidney injury (AKI) is an important complication associated with coronary angiography, percutaneous coronary intervention, and computed tomography studies. The increasing utilization of contrast agents for imaging makes the importance of this complication even greater. Patients can be risk stratified for the risk of contrast-induced AKI by several clinical factors including hypotension, renal function, age, advanced heart failure, anemia, and diabetes mellitus. Contrast volume is also an important and modifiable risk factor for AKI. For the prevention of contrast-induced AKI, multiple approaches have been tried. The most effective prevention strategy is hydration. Normal saline has been the standard, but other options such as sodium bicarbonate may be a reasonable alternative. Further studies will be required to clarify the best preventive strategies.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterization procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterization personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterization laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterization laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

Allergic reactions to clopidogrel and cross-reactivity to other agents.

Clopidogrel is a widely used antiplatelet agent, particularly after coronary stent implantation. About 1% of patients have allergic or hematologic adverse reactions to clopidogrel. This has important therapeutic implications, as premature discontinuation of clopidogrel is the strongest risk factor for stent thrombosis. Clopidogrel allergy most commonly manifests as a rash. It is important to distinguish this from other causes of rash occurring in patients who have had a recent coronary stent. Although antihistamines and short-term oral corticosteroids are effective in treating most clopidogrel hypersensitivity reactions, some persistent reactions may require discontinuation of clopidogrel. When discontinuation of clopidogrel is required, substitution with an alternative thienopyridine such as ticlopidine traditionally has been performed. However, a recent study suggests that there may be as high as a 27% risk of recurrence of non-life-threatening allergic reactions in such patients, which are usually similar to the allergic reactions that occurred with clopidogrel. No data are available regarding the frequency of cross-reactivity to prasugrel and ticagrelor; these may be potential therapeutic options in some patients.

SCAI consensus document on occupational radiation exposure to the pregnant cardiologist and technical personnel.

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterisation procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterisation personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the foetus of pregnant women in the cardiac catheterisation laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterisation laboratory. However, radiation exposure amongst pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted.

Ten-year trends, predictors and outcomes of mechanical circulatory support in percutaneous coronary intervention for acute myocardial infarction with cardiogenic shock.

AIMS: There are limited data on the trends and outcomes of mechanical circulatory support (MCS)-assisted early percutaneous coronary intervention (PCI) in acute myocardial infarction with cardiogenic shock (AMI-CS). In this study, we sought to assess the use, temporal trends, and outcomes of percutaneous MCS-assisted early PCI in AMI-CS. METHODS AND RESULTS: Using the National Inpatient Sample database from 2005-2014, a retrospective cohort of AMI-CS admissions receiving early PCI (hospital day zero) was identified. MCS use was defined as intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD) and extracorporeal membrane oxygenation (ECMO) support. Outcomes of interest included in-hospital mortality, resource utilisation, trends and predictors of MCS-assisted PCI. Of the 110,452 admissions, MCS assistance was used in 55%. IABP, pLVAD and ECMO were used in 94.8%, 4.2% and 1%, respectively. During 2009-2014, there was a decrease in MCS-assisted PCI due to a decrease in IABP, despite an increase in pLVAD and ECMO. Younger age, male sex, lower comorbidity, and cardiac arrest independently predicted MCS use. MCS-assisted PCI was predictive of higher in-hospital mortality (31% vs 26%, adjusted odds ratio 1.23 [1.19-1.27]; p<0.001) and greater resource utilisation. IABP-assisted PCI had lower in-hospital mortality and lesser resource utilisation compared to pLVAD/ECMO. CONCLUSIONS: MCS-assisted PCI identified a sicker AMI-CS cohort. There was a decrease in IABP and an increase in pLVAD/ECMO.

Pregnancy-Associated Myocardial Infarction: Prevalence, Causes, and Interventional Management.

Pregnancy-associated myocardial infarction is a primary contributor to maternal cardiovascular morbidity and mortality. Specific attention to the cause of myocardial infarction, diagnostic evaluation, treatment strategies, and postevent care is necessary when treating women with pregnancy-associated myocardial infarction. This review summarizes the current knowledge, consensus statements, and essential nuances.

Association of Pregnancy With Recurrence of Spontaneous Coronary Artery Dissection Among Women With Prior Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) is a notable cause of acute coronary syndrome in women of childbearing age. Objective: To test the hypothesis that pregnancy after SCAD is associated with recurrent SCAD. Design, Setting, and Participants: Three study designs were implemented: a case series of women with pregnancy after SCAD; a nested case-control study comparing patients with recurrent SCAD to matched controls without recurrent SCAD; and a cohort study. Women with SCAD who were of childbearing potential and enrolled into the Mayo Clinic SCAD Registry from August 30, 2011, to April 4, 2019, were included in the study. Patients with coronary dissections associated with iatrogenesis, trauma, or atherosclerosis were not enrolled. Exposures: Pregnancy after SCAD. Main Outcomes and Measures: The primary outcome was SCAD recurrence, defined as an acute coronary syndrome or cardiac arrest due to new SCAD. Other demographic measures collected included age, year of SCAD occurrence, and comorbidities. Results: The cohort included 636 women of childbearing potential. Twenty-three of those women had a total of 32 pregnancies after SCAD. The median (interquartile range) age of women with pregnancy after SCAD was 38 years (34-40 years), and 20 (87%) were White. In the nested case-control study, 92 cases of recurrent SCAD were matched to 158 controls. There was no significant difference in exposure to subsequent pregnancies in the women with recurrent SCAD as compared with matched controls (2 of 92 [2%] vs 13 of 158 [8%]; P = .06). In the overall cohort of 636 patients, recurrent SCAD was present in 122 patients with a Kaplan-Meier 5-year SCAD recurrence estimate of 14.8%. The Cox analysis showed no significant association between subsequent pregnancy and SCAD recurrence with a nonsignificant hazard ratio of 0.38 (95% CI, 0.09-1.6) when controlling for age at first SCAD, year of first SCAD, and fibromuscular dysplasia. Conclusions and Relevance: This study found that most women tolerated pregnancy and lactation after SCAD without evidence for increased risk of SCAD recurrence when compared with women with a history of SCAD who did not experience pregnancy. Although this study is reassuring and indicates complex contributors to SCAD recurrence, the results need to be interpreted prudently because of study selection bias and the small total number of women who became pregnant after SCAD. The notable hemodynamic changes that occur with pregnancy and severe presentation of pregnancy-associated SCAD are reasons for concern when considering pregnancy after SCAD.

Sex and Gender Disparities in the Management and Outcomes of Acute Myocardial Infarction-Cardiogenic Shock in Older Adults.

OBJECTIVE: To evaluate outcomes by sex in older adults with cardiogenic shock complicating acute myocardial infarction (AMI-CS). MATERIALS AND METHODS: A retrospective cohort of older (≥75 years) AMI-CS admissions during January 1, 2000, to December 31, 2014, was identified using the National Inpatient Sample. Interhospital transfers were excluded. Use of angiography, percutaneous coronary intervention (PCI), mechanical circulatory support (MCS), and noncardiac interventions was identified. The primary outcome was in-hospital mortality stratified by sex, and secondary outcomes included temporal trends of prevalence, in-hospital mortality, use of cardiac and noncardiac interventions, hospitalization costs, and length of stay. RESULTS: In this 15-year period, there were 134,501 AMI-CS admissions 75 years or older, of whom 51.5% (n=69,220) were women. Women were on average older, were more often Hispanic or nonwhite race, and had lower comorbidity, acute organ failure, and concomitant cardiac arrest. Compared with older men (n=65,281), older women (n=69,220) had lower use of coronary angiography (55.4% [n=35,905] vs 49.2% [n=33,918]), PCI (36.3% [n=23,501] vs 34.4% [n=23,535]), MCS (34.3% [n=22,391] vs 27.2% [n=18,689]), mechanical ventilation, and hemodialysis (all P<.001). Female sex was an independent predictor of higher in-hospital mortality (adjusted odds ratio, 1.05; 95% CI, 1.02-1.08; P<.001) and more frequent discharges to a skilled nursing facility. In subgroup analyses of ethnicity, presence of cardiac arrest, and those receiving PCI and MCS, female sex remained an independent predictor of increased mortality. CONCLUSION: Female sex is an independent predictor of worse in-hospital outcomes in older adults with AMI-CS in the United States.

A Dangerous Dilemma: Thrombus in Transit During Pregnancy.

Pregnancy is associated with venous thromboembolism. Occasionally, thrombus can become entrapped across a patent foramen ovale, with risk of systemic embolism. This report presents a case of a pregnant woman who had thrombus in transit diagnosed by echocardiography, which was successfully removed by surgical thrombectomy. (Level of Difficulty: Intermediate.).

The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.

BACKGROUND: Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. METHODS: Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]). RESULTS: Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). CONCLUSIONS: Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.

Prevalence and Clinical Factors of Migraine in Patients With Spontaneous Coronary Artery Dissection.

Background Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome predominantly in women without usual cardiovascular risk factors. Many have a history of migraine headaches, but this association is poorly understood. This study aimed to determine migraine prevalence among SCAD patients and assess differences in clinical factors based on migraine history. Methods and Results A cohort study was conducted using the Mayo Clinic SCAD "Virtual" Multi-Center Registry composed of patients with SCAD as confirmed on coronary angiography. Participant-provided data and records were reviewed for migraine history, risk factors, SCAD details, therapies, and outcomes. Among 585 patients (96% women), 236 had migraine history; the lifetime and 1-year prevalence of migraine were 40% and 26%, respectively. Migraine was more common in SCAD women than comparable literature-reported female populations (42% versus 24%, P<0.0001; 42% versus 33%, P<0.0001). Among all SCAD patients, those with migraine history were more likely to be female (99.6% versus 94%; P=0.0002); have SCAD at a younger age (45.2±9.0 years versus 47.6±9.9 years; P=0.0027); have depression (27% versus 17%; P=0.025); have recurrent post-SCAD chest pain at 1 month (50% versus 39%; P=0.035); and, among those assessed, have aneurysms, pseudoaneurysms, or dissections (28% versus 18%; P=0.018). There was no difference in recurrent SCAD at 5 years for those with versus without migraine (15% versus 19%; P=0.39). Conclusions Many SCAD patients have a history of migraine. SCAD patients with migraine are younger at the time of SCAD; have more aneurysms, pseudoaneurysms, and dissections among those imaged; and more often report a history of depression and post-SCAD chest pain. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01429727, NCT01427179.

Prognostic Utility of Stress Testing and Cardiac Biomarkers in Menopausal Women at Low to Intermediate Risk for Coronary ARTery Disease (SMART Study): 5-Year Outcome.

BACKGROUND: In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. OBJECTIVES: To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. MATERIALS AND METHODS: From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity®, Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. RESULTS: A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without (p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9-61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1-7.3], p = 0.028). CONCLUSIONS: sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.