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Ischemic heart disease (IHD) is the leading cause of mortality in women. While traditional cardiovascular risk factors play an important role in the development of IHD in women, women may experience sex-specific IHD risk factors and pathophysiology, and thus female-specific risk stratification is needed for IHD prevention, diagnosis, and treatment. Emerging data from the past 2 decades have significantly improved the understanding of IHD in women, including mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries. Despite this progress, sex differences in IHD outcomes persist, particularly in young women. This review highlights the contemporary understanding of coronary arterial function and disease in women with no obstructive coronary arteries, including coronary anatomy and physiology, mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries, noninvasive and invasive diagnostic strategies, and management of IHD.

Multifocal fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection are both sex-biased diseases disproportionately affecting women over men in a 9:1 ratio. Traditionally known in the context of renovascular hypertension, recent advances in knowledge about FMD have demonstrated that FMD is a systemic arteriopathy presenting as arterial stenosis, aneurysm, and dissection in virtually any arterial bed. FMD is also characterized by major cardiovascular presentations including hypertension, stroke, and myocardial infarction. Similar to FMD, spontaneous coronary artery dissection is associated with a high prevalence of extracoronary vascular abnormalities, including FMD, aneurysm, and extracoronary dissection, and recent studies have also found genetic associations between the two diseases. This review will summarize the relationship between FMD and spontaneous coronary artery dissection with a focus on common clinical associations, histopathologic mechanisms, genetic susceptibilities, and the biology of these diseases. The current status of disease models and critical future research directions will also be addressed.

A growing number of patients undergoing percutaneous coronary intervention (PCI) with stent implantation also have atrial fibrillation. This poses challenges for their optimal antithrombotic management because patients with atrial fibrillation undergoing PCI require oral anticoagulation for the prevention of cardiac thromboembolism and dual antiplatelet therapy for the prevention of coronary thrombotic complications. The combination of oral anticoagulation and dual antiplatelet therapy substantially increases the risk of bleeding. Over the last decade, a series of North American Consensus Statements on the Management of Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention have been reported. Since the last update in 2018, several pivotal clinical trials in the field have been published. This document provides a focused updated of the 2018 recommendations. The group recommends that in patients with atrial fibrillation undergoing PCI, a non–vitamin K antagonist oral anticoagulant is the oral anticoagulation of choice. Dual antiplatelet therapy with aspirin and a P2Y12inhibitor should be given to all patients during the peri-PCI period (during inpatient stay, until time of discharge, up to 1 week after PCI, at the discretion of the treating physician), after which the default strategy is to stop aspirin and continue treatment with a P2Y12inhibitor, preferably clopidogrel, in combination with a non–vitamin K antagonist oral anticoagulant (ie, double therapy). In patients at increased thrombotic risk who have an acceptable risk of bleeding, it is reasonable to continue aspirin (ie, triple therapy) for up to 1 month. Double therapy should be given for 6 to 12 months with the actual duration depending on the ischemic and bleeding risk profile of the patient, after which patients should discontinue antiplatelet therapy and receive oral anticoagulation alone.

Background A significant proportion of patients with spontaneous coronary artery dissection (SCAD) have ongoing chronic chest pain despite healing of their dissection. We sought to determine whether coronary microvascular dysfunction contributes to post‐SCAD chronic chest pain by performing coronary reactivity testing in the cardiac catheterization laboratory. Methods and Results Eighteen patients consented to coronary reactivity testing at least 3 months post‐SCAD. Coronary flow reserve (CFR) and index of microcirculatory resistance were measured in the previously affected SCAD artery and 1 non‐SCAD artery. CFR 25 units. Seventeen women underwent coronary reactivity testing (1 had chronic dissection and was excluded). All presented with myocardial infarction and 2 underwent coronary stenting during the initial SCAD event. Fibromuscular dysplasia was present in 70.6% upon screening renal, iliac, and cerebrovascular arteries. Twelve patients (70.6%) had CFR 25 in at least 1 artery. There was no difference in the frequency of a low CFR measurement between SCAD and non‐SCAD arteries. Conclusions Among patients with chronic chest pain after an SCAD event, >70% had coronary microvascular dysfunction as indicated by abnormal CFR or index of microcirculatory resistance in at least 1 coronary artery on invasive coronary reactivity testing. Presence of coronary microvascular dysfunction in both SCAD and non‐SCAD arteries suggests that underlying microvascular abnormalities from vasculopathies such as coronary fibromuscular dysplasia may be the underlying etiology.

Spontaneous coronary artery dissection (SCAD) remains an infrequent, elusive, and challenging clinical entity of unknown etiology eight decades after its initial description. Our understanding of the pathophysiology of SCAD, initially limited to information from early pathological studies, case reports, and very short series, has been enriched recently by relatively large contemporary series of patients studied prospectively. The typical presentation involves a young woman without coronary risk factors suffering an acute coronary syndrome but, actually, most patients are middle-aged and have coronary risk factors. A high number of conditions have been related to SCAD, but fibromuscular dysplasia has shown a major intriguing association with potential pathophysiological implications. SCAD may present (a) with an intimal tear and the classic angiographic 'flap' leading to the appearance of two lumens (true and false), or (b) without an intimal rupture, as an intramural hematoma. An increased clinical awareness together with new diagnostic tools have led to a major surge in the diagnosis of SCAD. High-resolution intracoronary techniques provide unique diagnostic insights into the underlying pathophysiology and facilitate identification of the disease in patients misdiagnosed previously. After the initial acute ischemic insult, most patients stabilize and have a benign clinical course and eventually experience spontaneous healing of the vessel wall during follow-up. However, recurrences may still occur in up to 10-20% of cases. Accordingly, a conservative medical management (watchful waiting strategy) has been recommended as the initial approach. Revascularization remains particularly challenging and may be associated with suboptimal results, acute complications, and poor long-term outcome. Nevertheless, in patients with ongoing or refractory ischemia and adequate anatomy, revascularization should be attempted. Some novel and attractive coronary interventions have been proposed in this uniquely challenging anatomic scenario. This review aims to present a comprehensive and contemporary update on this elusive and intriguing clinical entity.

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.

Background: Surveillance after left atrial appendage (LAA) closure is important to assess for device success and complications. There is limited data on the role of cardiac computerized tomography angiography (CCTA) for LAA device monitoring. Methods: We retrospectively analyzed consecutive patients with non-valvular atrial fibrillation who underwent LAA closure who had both trans-esophageal echocardiography (TEE) and CCTA performed post-LAA closure. Prospective cardiac-gated CCTA were performed with Toshiba 320-detector or Siemens 2nd generation 128-slice dual-source scanners. We assessed for residual contrast patency of the LAA by comparing linear attenuation coefficient (Hounsfield unit, HU) in the LAA and left atrium (LA) on CCTA. Residual contrast patency was categorized as due to peri-device leak (presence of ostial gap) or fabric leak (diffusion of contrast through device membrane). We also assessed for device compression, thrombus and pericardial effusion on CCTA. These were compared to TEE findings. Results: Sixty-one patients underwent CCTA at median 93.5d (1-267) post-LAA closure (55 WATCHMAN, 4 Amulet, 2 ACP). Post-procedural TEE was done at median 93d (0-289). The median age was 77.5yrs (60-88) and median CHADS-VASc score 4 (2-8). Procedural success was 100%. On TEE, the presence of any peri-device leak was 26 (41.9%), with >3mm leak observed in 10/62 (16.1%), and >5mm observed in none. The presence of residual contrast patency in the LAA was observed in 36/61 (59%) on CCTA, of these, 29 (80.5%) had peri-device leak, and 7 (19.4%) had fabric leak. The median linear attenuation coefficient in patients with residual contrast patency was 328 (133-652) HU, and all had >100 HU in the LAA and HU attenuation ratio LA/LAA of >0.25. Median maximum device compression was 5.7% in those with peri-device leak, and 19.4% (p=0.027) for those without peri-device leak on CCTA. Among patients with peri-device leak on CCTA, 89.6% had peri-device leak on TEE, with corresponding 93.8% sensitivity, 69.9% specificity, and AUC=0.82 (95% CI 0.72-0.93). Conclusions: CCTA is more sensitive than TEE for assessing peri-device leak after LAA closure. Greater device compression appears to be associated with lower incidence of peri-device leak.

Acute myocardial infarction (MI) is a rare complication of pregnancy affecting 6 per 100 000 deliveries based on the US Nationwide Inpatient Sample hospital administrative database, and this risk seems to be 3- to 4-fold higher compared with that of nonpregnant women of similar age.1 Furthermore, an updated analysis from the same database reported pregnancy-associated spontaneous coronary artery dissection (PASCAD) affecting 1.81 per 100 000 pregnancies, although this may represent an underestimation of the true prevalence.2 A contemporary literature review of 134 cases of pregnancy-related MI identified spontaneous coronary artery dissection (SCAD) as the most important and underlying cause in ≈40%, being more common than atherosclerosis, thromboembolism, vasospasm, or Takotsubo syndrome in this cohort.3 Even though SCAD is an infrequent cause of MI in the general population (estimated at 1.7%–4%), its relative prominence is magnified in the enriched population of young women, accounting for 24% to 35% of MI in women aged ≤50 years old4 and even higher prevalence in women with pregnancy-related MI.3 Furthermore, previous reports also alluded to higher acuity and worse prognosis with PASCAD compared with nonpregnancy-related SCAD cases.5 Therefore, while PASCAD accounts for only

Background— Nonatherosclerotic spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocardial infarction in young women. The frequency of predisposing and precipitating conditions and cardiovascular outcomes remains poorly described. Methods and Results— Patients with NA-SCAD prospectively evaluated (retrospectively or prospectively identified) at Vancouver General Hospital were included. Angiographic SCAD diagnosis was confirmed by 2 experienced interventional cardiologists and categorized as type 1 (multiple lumen), 2 (diffuse stenosis), or 3 (mimic atherosclerosis). Fibromuscular dysplasia screening of renal, iliac, and cerebrovascular arteries were performed with angiography or computed tomographic angiography/MR angiography. Baseline, predisposing and precipitating conditions, angiographic, revascularization, in-hospital, and long-term events were recorded. We prospectively evaluated 168 patients with NA-SCAD. Average age was 52.1±9.2 years, 92.3% were women (62.3% postmenopausal). All presented with myocardial infarction. ECG showed ST-segment elevation in 26.1%, and 3.6% had ventricular tachycardia/ventricular fibrillation arrest. Fibromuscular dysplasia was diagnosed in 72.0%. Precipitating emotional or physical stress was reported in 56.5%. Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3. The majority (134/168) were initially treated conservatively. Overall, 6 of 168 patients had coronary artery bypass surgery and 33 of 168 had percutaneous coronary intervention in-hospital. Of those treated conservatively (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram ≥26 days later had spontaneous healing. Two-year major adverse cardiac events were 16.9% (retrospectively identified group) and 10.4% (prospectively identified group). Recurrent SCAD occurred in 13.1%. Conclusions— Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic SCAD. Conservative therapy was associated with spontaneous healing. NA-SCAD survivors are at risk for recurrent cardiovascular events, including recurrent SCAD.

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist, either clopidogrel or the newer more potent agents prasugrel or ticagrelor, is standard therapy in patients receiving a coronary stent and those with a recent acute coronary syndrome. Switching antiplatelet drug regimen may be required in some patients for efficacy, safety, adherence, and cost considerations. However, there are potential concerns when switching from one agent to another that gaps in effective antiplatelet inhibition could lead to thrombotic events, and overlap of agents might cause excessive platelet inhibition thereby increasing the risk of bleeding. This review considers pharmacodynamic and clinical data to guide clinicians when switching between antiplatelet drugs is considered. Loading dose of the new agent should be considered in nearly all situations to avoid any possible gap in adequate platelet inhibition, as overlap of the 2 agents is unlikely to result in bleeding in excess of that with the more potent drug.

Background: We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD). Angiographic manifestation of coronary FMD aside from dissection was reported to be rare. However, we observed several non-dissection coronary angiographic abnormalities in patients with multifocal FMD. Methods: Baseline demographics and imaging of patients with suspected non-dissection coronary FMD at Vancouver General Hospital were retrospectively reviewed. Presence of multifocal FMD in non-coronary territories was confirmed by 3 specialists. Coronary angiograms with suspected coronary FMD changes (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for: (1) irregular stenosis (beading) - multiple areas of stenosis in a focal or diffuse pattern and with/without systolic accentuation, (2) smooth stenosis - diffuse or focal, (3) segmental dilatation/ectasia, and (4) tortuosity. Optical coherence tomography (OCT), if performed, were reviewed by 2 specialists. Results: Of 28 patients with multifocal FMD and suspected coronary involvement on angiography, 23 were women (82.1%), mean age was 58.6 ± 9.5, and mean BMI was 24.6. Sixteen presented with myocardial infarction (10 due to SCAD), 12 underwent angiography for stable or atypical angina. The observed coronary angiographic abnormalities were: irregular stenosis (beading) in 14 (12 diffuse, 2 focal, 3 with systolic accentuation), smooth stenosis in 6 (4 diffuse, 2 focal), segmental dilatation/ectasia in 14 (majority with multi-segmental, diffuse enlargement in an entire vessel), and tortuosity in 25 cases. Fourteen patients had OCT of the abnormal segments showing abnormalities distinct from atherosclerosis. These included multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with disorganized fibrotic thickening, proteoglycan accumulation, macrophage infiltration, loss of elastic membranes, and cavitation. Conclusions: This is the first case series describing angiographic manifestations of coronary FMD, which can be categorized into irregular stenosis, smooth stenosis, dilatation and tortuosity, representing features that are additional to dissection.

Background: There is limited data with WATCHMAN for left atrial appendage (LAA) closure in patients with nonvalvular atrial fibrillation (AF) and contraindications to anticoagulation. The purpose of this study was to evaluate the safety and efficacy of WATCHMAN in our early Canadian experience. Methods: We report our consecutive series of patients who underwent WATCHMAN implantation at 4 Canadian centers (Vancouver General Hospital, Montreal Heart Institute, Hamilton General Hospital and Ottawa Heart Institute). Indications for LAA closure were CHADS2≥1, and contraindication/intolerance to or failure on anticoagulation. All cases were done under general anesthesia and TEE guidance. Majority of patients received dual antiplatelet therapy (DAPT) for 3-6 months after implant. Follow-up TEE was typically performed at 1-6 months post-procedure. Results: Ninety patients underwent LAA closure with WATCHMAN from May 2013 to June 2015. The mean age was 75.0 ± 7.9. The mean CHADS2 score was 2.9 ± 1.2, CHADS-VASc score was 4.4 ± 1.5, and HASBLED score was 3.2 ± 1.2. Permanent AF was present in 66.7% and paroxysmal AF in 33.3%. Indications for LAA closure were prior bleeding in 81 patients (90.0%; 74 major bleeding, and 7 minor bleeding), 9 were deemed high-risk for bleeding (renal failure, cirrhosis, labile INR, esophageal ulcers, on DAPT), and 1 with recurrent strokes on warfarin. Procedural success was 97.8% (88/90), with one device embolization (snared percutaneously) and one implant failure due to inadequate LAA depth. There was no procedural stroke/TIA, death, MI, or cardiac tamponade. There were 3 major bleeding that required transfusions. Mean hospital stay was 1.4 ± 1.8 days. Antithrombotic therapy post-implant included DAPT in 66/90 (73.3%), anticoagulant in 21/90 (5 warfarin, 16 direct anticoagulant), and aspirin alone in 3/90. Follow-up TEE was available in 53 patients, there was 1 device-associated thrombus (treated successfully with anticoagulation), and 18 peri-device leaks (all Conclusion: In our early Canadian experience, WATCHMAN for LAA closure in patients contraindicated to anticoagulation is safe and effective.

Background: Spontaneous coronary artery dissection (SCAD) is an infrequent but important cause of myocardial infarction (MI) in women. Chronic exposure to hormonal therapy, fluctuation in hormonal levels, and a history of multiple pregnancies had been postulated to predispose to SCAD. However, these were not well described in the literature. Methods: Women with SCAD who have consented and are prospectively followed in our Vancouver General Hospital SCAD registries are included in this study. Their background hormonal exposure, pregnancy, and gynaecological histories were extracted from questionnaires, clinical histories, and medical records. These were correlated to in-hospital and long-term outcomes. Results: We included 187 women with SCAD, with mean age 52.6 ± 8.7 years. The majority were Caucasian (83.4%) and 74.0% had fibromuscular dysplasia. All patients presented with MI. Mean number of pregnancy in this cohort was 2.5, with 45 (24.1%) and 25 (13.4%) having ≥4 and ≥5 pregnancies, respectively. Mean number of live births (parity) was 1.8, with 52 (27.8%) having ≥3 births, and 16 (8.6%) having ≥4 births. There were 3 post-partum SCAD ( Conclusion: Significant proportion of women with SCAD had exposure to hormonal therapy or had multiple pregnancies/births. Patients actively on hormonal therapy appeared to have higher recurrent SCAD events at follow-up.

Background— Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel’s metabolism to active metabolite, thus attenuating its inhibition of platelet aggregation ex vivo. However, the clinical impact of this interaction has not been evaluated. Methods and Results— Clopidogrel for the Reduction of Events During Observation (CREDO) was a double-blind, placebo-controlled, randomized trial comparing pretreatment (300 mg) and 1-year (75 mg/d) clopidogrel therapy (clopidogrel) with no pretreatment and 1-month clopidogrel therapy (75 mg/d) (control) after a planned percutaneous coronary intervention. All patients received aspirin. The 1-year primary end point was a composite of death, myocardial infarction, and stroke. We performed a post hoc analysis to evaluate the clinical efficacy of concomitant clopidogrel and statin administration, categorizing baseline statin use to those predominantly CYP3A4-metabolized (atorvastatin, lovastatin, simvastatin, and cerivastatin) (CYP3A4-MET) or others (pravastatin and fluvastatin) (non-CYP3A4-MET). Of the 2116 patients enrolled, 1001 received a CYP3A4-MET and 158 a non-CYP3A4-MET statin. For the overall study population, the primary end point was significantly reduced in the clopidogrel group (8.5% versus 11.5%, RRR 26.9%; P =0.025). This clopidogrel benefit was similar with statin use, irrespective of treatment with a CYP3A4-MET (7.6% clopidogrel, 11.8% control, RRR 36.4%, 95% CI 3.9 to 57.9; P =0.03) or non-CYP3A4-MET statin (5.4% clopidogrel, 13.6% control, RRR 60.6%, 95% CI −23.9 to 87.4; P =0.11). Patients given atorvastatin or pravastatin had similar 1-year event rates. Additionally, concomitant therapy with statins had no impact on major or minor bleeding rates. Conclusions— Although ex vivo testing has suggested a potential negative interaction when coadministering a CYP3A4-metabolized statin with clopidogrel, this was not clinically observed statistically in a post hoc analysis of a placebo-controlled study.

The coronary arteries carry oxygen- and nutrient-rich blood to the heart, which allows it to pump and supply blood to the body. The coronary arteries can become blocked by various processes related to cholesterol (atherosclerotic) or other causes (nonatherosclerotic), which can cause heart attacks when the blockages are severe enough to impede blood flow to the heart. Although the atherosclerotic form is most common, nonatherosclerotic blockages (especially dissections/tears) are increasingly recognized as important causes of heart attacks, particularly in women. This article focuses on spontaneous coronary artery dissection (SCAD). SCAD is defined as a tear in the coronary arterial wall that is not related to trauma or medical instrumentation. This spontaneous tear can result from a disruption of the innermost lining of the arterial wall, causing blood to rush in from the lumen (center channel of the artery) into the arterial wall. Alternatively, separation of the arterial walls can occur as a result of bleeding caused by spontaneous rupture of small vessels that feed the arterial wall. The buildup of blood inside the arterial wall compresses the lumen, blocking blood flow to the heart. SCAD is considered to be rare in the general population, although it has been underdiagnosed, and its true prevalence is unknown. Overall, it is an infrequent cause of and accounts for only up to 4% of heart attacks.1 However, SCAD proportionally causes a higher number of heart attacks in young women; ≈25% of women ≤50 years old had heart attacks caused by SCAD in 1 series.2 SCAD affects predominantly women in ≈90% …

Background: The presence of aspirin and clopidogrel resistance is increasingly recognized. We seek to evaluate if patients with aspirin and/or clopidogrel resistance are predisposed to myonecrosis following percutaneous coronary interventions (PCI). Methods: This study is performed as a substudy of the Brief-PCI, which randomized 620 patients to 18hr or 2hr infusion of eptifibatide following PCI. To be eligible for our substudy, patients have to be pretreated with aspirin (≥5 days) and clopidogrel (either 75mg/d ≥5 days, or 300mg loading ≥6 hr), and have not received a glycoprotein IIb/IIIa inhibitor within the past 48hrs. Bedside point-of-care platelet aggregometry using Accumetrics VerifyNow™ Aspirin and Clopidogrel assays were performed at baseline prior to PCI. Patients with aspirin reaction unit (ARU) ≥550 were labeled as “aspirin resistant”. Patients with percent inhibition ≤20% on the VerifyNow™ Clopidogrel assays were labeled as “clopidogrel resistant”. Our primary endpoint is the prevalence of myonecrosis within 24hrs post-PCI (defined as elevation of Troponin I >1μg/L when baseline levels are negative, or peak CK-MB >3 times upper limit of normal and >50% higher than baseline value). Results: We enrolled 203 patients, of which 181 had aspirin resistance assessed, 188 had clopidogrel resistance assessed, and 169 had both assessed. There were 5% ± 1.6% who were aspirin resistant, 29% ± 3.3% who were clopidogrel resistant, and 1% ± 0.8% who were resistant to both. The overall prevalence of myonecrosis within 24hrs of PCI was 9% ± 2%. Patients who were resistant to both aspirin and clopidogrel had a higher prevalence of myonecrosis compared to those who had normal response (50% vs. 8%, p=0.031). There was no difference in myonecrosis prevalence among aspirin resistant patients compared to those with normal aspirin response (11% vs. 8%, p=0.754), or among clopidogrel resistant patients compared to those with normal clopidogrel response (11% vs. 7%, p=0.390). The mean ARU and percent inhibition was not different between those with or without myonecrosis. Conclusion: Our data suggests that only a small proportion of patients were resistant to both aspirin and clopidogrel, and these patients may have a higher prevalence of myonecrosis following PCI.