Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

Outcomes of Percutaneous Coronary Intervention in Patients with Spontaneous Coronary Artery Dissection.

OBJECTIVES: To compare outcomes of percutaneous coronary intervention (PCI) in spontaneous coronary artery dissection (SCAD) patients versus conservative therapy. BACKGROUND: SCAD is an important cause of myocardial infarction (MI) in young-to-middle-aged women. Percutaneous coronary intervention (PCI) is often pursued, but outcomes compared to conservative therapy are unclear. METHODS: 403 nonatherosclerotic SCAD patients were enrolled between 2011 and 2017 and prospectively followed up in our Vancouver General Hospital registries. Detailed baseline, hospital, PCI, and outcomes were recorded. We explored the outcomes of SCAD patients who underwent PCI during their initial presentation. RESULTS: PCI was performed in 75 patients, the average age was 48.9 ± 10.1 yrs, and 94.7% were women. All presented with MI; 50.7% STEMI, 49.3% NSTEMI, and 13.3% had VT/VF. PCI was successful in 34.7%, partially successful in 37.3%, and unsuccessful in 28.0%. Stents were deployed in 73.3%, 16.0% had balloon angioplasty alone, 10.7% had wiring attempts only, and 5.3% required bailout surgery. Major adverse cardiovascular event rates (MACE) were significantly higher with the PCI group in hospital (29.3% versus 2.8%, p < 0.001), and at median follow-up of 3.7 yrs (58.7% versus 22.6% (p < 0.001) compared to the non-PCI group. CONCLUSION: PCI in SCAD patients was associated with high failure rate and MACE in hospital and at long-term follow-up. These findings support the recommendation of conservative therapy as first-line management unless high-risk features are present.

Ranolazine for Symptomatic Management of Microvascular Angina.

BACKGROUND: Ranolazine is approved in the United States and Europe for chronic stable angina. Microvascular angina (MVA) is defined as angina with no obstructive coronary artery disease. STUDY QUESTION: Our objective was to assess the effectiveness of ranolazine at improving angina scores and quality of life in a Canadian cohort with severe refractory angina due to MVA. STUDY DESIGN: We administered questionnaires to 31 patients at baseline and after at least 6 weeks of ranolazine treatment. MEASURES AND OUTCOMES: Validated, clinically significant changes for each Seattle Angina Questionnaire domain and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form were obtained from the literature. Score changes between baseline and postranolazine use were analyzed using sign test. RESULTS: Patients were mostly female (27 of 31 patients) with a median age of 57 years. After initiation of ranolazine treatment, patients experienced improvements in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form scores (80.6%; P < 0.01) and in 3 of the 4 domains of the Seattle Angina Questionnaire (physical limitation: 73.3%; P = 0.02; treatment satisfaction: 80.6%; P < 0.01; and disease perception: 77.4%; P < 0.01). Patients were less likely to have interactions with the health care system after ranolazine treatment as compared with before (35.5% vs. 93.5%; P < 0.01). CONCLUSIONS: Ranolazine significantly improves symptom control and quality of life in patients with MVA and severe refractory angina and reduces their interaction with the health care system. Given the potentially debilitating effect of chronic angina in MVA, ranolazine may be an effective treatment option.

Canadian spontaneous coronary artery dissection cohort study: in-hospital and 30-day outcomes.

AIMS: Spontaneous coronary artery dissection (SCAD) was underdiagnosed and poorly understood for decades. It is increasingly recognized as an important cause of myocardial infarction (MI) in women. We aimed to assess the natural history of SCAD, which has not been adequately explored. METHODS AND RESULTS: We performed a multicentre, prospective, observational study of patients with non-atherosclerotic SCAD presenting acutely from 22 centres in North America. Institutional ethics approval and patient consents were obtained. We recorded baseline demographics, in-hospital characteristics, precipitating/predisposing conditions, angiographic features (assessed by core laboratory), in-hospital major adverse events (MAE), and 30-day major adverse cardiovascular events (MACE). We prospectively enrolled 750 SCAD patients from June 2014 to June 2018. Mean age was 51.8 ± 10.2 years, 88.5% were women (55.0% postmenopausal), 87.7% were Caucasian, and 33.9% had no cardiac risk factors. Emotional stress was reported in 50.3%, and physical stress in 28.9% (9.8% lifting >50 pounds). Predisposing conditions included fibromuscular dysplasia 31.1% (45.2% had no/incomplete screening), systemic inflammatory diseases 4.7%, peripartum 4.5%, and connective tissue disorders 3.6%. Most were treated conservatively (84.3%), but 14.1% underwent percutaneous coronary intervention and 0.7% coronary artery bypass surgery. In-hospital composite MAE was 8.8%; peripartum SCAD patients had higher in-hospital MAE (20.6% vs. 8.2%, P = 0.023). Overall 30-day MACE was 8.8%. Peripartum SCAD and connective tissue disease were independent predictors of 30-day MACE. CONCLUSION: Spontaneous coronary artery dissection predominantly affects women and presents with MI. Despite majority of patients being treated conservatively, survival was good. However, significant cardiovascular complications occurred within 30 days. Long-term follow-up and further investigations on management are warranted.

Case reports of coronary fibromuscular dysplasia and spontaneous coronary artery dissections.

Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome especially in women. The most common underlying predisposing cause of SCAD is fibromuscular dysplasia (FMD), a non-inflammatory arteriopathy that results in weakening of the affected arteries, and can cause dissection or aneurysm. Coronary FMD (CFMD) was described as rare, and was shown to cause SCAD in histopathological case reports. Unfortunately, CFMD is challenging to diagnose on coronary angiography, as the findings can be similar to other causes of coronary artery disease. Therefore, we illustrate two case examples of CFMD on coronary angiography, and highlight findings on optical coherence tomography to aid diagnosis.

Development of a Porcine Model of Coronary Stenosis Using Fully Percutaneous Techniques Suitable For Performing Cardiac Computed Tomography, CT-Perfusion Imaging and Fractional Flow Reserve.

BACKGROUND: The aim of this study was to develop and describe percutaneous coronary angiographic techniques to create a porcine model of acute coronary stenosis with methacrylate plugs that can by assessed using fractional flow reserve (FFR), invasive coronary angiography and coronary computed tomographic (CT) perfusion imaging without introducing artefacts associated with surgical models. METHODS: Following animal care and institutional approval and using percutaneous coronary catheterisation techniques within an animal laboratory we introduced precision drilled methacrylate plugs into one of the three main coronary arteries of 10 experimental female pigs. Coronary pressure wire measurements were performed across the experimental stenosis for the calculation of FFR. Invasive coronary angiograms were obtained in stenosed arteries. Animals were transported to a dual source CT scanner (Siemens Healthcare, Forcheim, Germany) and CT perfusion imaging was performed. RESULTS: Ten (10) pigs were investigated with seven data sets obtained. Three (3) pigs expired prior to CT imaging secondary to pneumothorax, high grade coronary stenosis with induced cardiac arrhythmia and iatrogenic air embolism. Graded coronary stenosis was produced in six pigs in the LAD (2), LCX (2) and RCA (2) territories and one animal served as a control. Fractional flow reserve ranged from 0.21 to 0.91. Myocardial blood flow derived from dynamic CT perfusion imaging ranged from 3.5 to 136.7ml/100ml of tissue/minute. No artefacts from the deployment of the methacrylate plug, nor the plug itself, were identified. CONCLUSIONS: Fully percutaneous preparation of a pig model of acute coronary stenosis is feasible and provides subjects for imaging that are free of surgically induced artefact. This technique is substantially less expensive than surgically induced coronary stenosis and can be performed using standard catheterisation techniques with mobile imaging equipment. The technique is extendable to produce multivessel acute coronary stenosis and can be used for multimodality imaging.

Clinical presentation of patients with spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an infrequent but important cause of myocardial infarction (MI) especially in younger women. However, the clinical presentation and the acuity of symptoms prompting invasive management in SCAD patients have not been described. Understanding these presenting features may improve SCAD diagnosis and management. METHODS: We reviewed SCAD patients who were prospectively followed at the Vancouver General Hospital SCAD Clinic. Their presenting symptoms and unstable features were obtained from detailed clinical histories and hospital admission documentation. Baseline characteristics, predisposing and precipitating conditions, angiographic findings, management strategies, in-hospital, and long-term events were recorded prospectively. RESULTS: We included 196 SCAD patients who had complete documentation of their presenting symptoms. The majority were women (178/196; 90.8%) and all presented with MI (24.0% STEMI). The most frequent presenting symptom was chest discomfort, reported by 96%. Other symptoms included arm pain (49.5%), neck pain (22.1%), nausea or vomiting (23.4%), diaphoresis (20.9%), dyspnea (19.3%), and back pain (12.2%). Ventricular tachycardia/fibrillation occurred in 8.1% (16/196), with 1.0% having cardiac arrest. The time from symptom onset to hospital presentation was 1.1 ± 3.0 days. NSTEMI patients had longer delay for coronary angiography compared with STEMI (2.0 ± 2.5 days vs. 0.8 ± 1.7 days, P = 0.002). Overall, 34.2% had unstable symptoms upon arrival for coronary angiography. Those with unstable symptoms were more likely to undergo repeat angiography (65.7% vs. 50.4%, P = 0.049), and repeat or unplanned revascularization (14.9% vs. 5.4%, P = 0.033) during acute hospitalization. CONCLUSION: Chest discomfort was the most frequent presenting symptom with SCAD and one-third had unstable symptoms prompting urgent invasive angiography. © 2017 Wiley Periodicals, Inc.

Angiographic appearance of spontaneous coronary artery dissection with intramural hematoma proven on intracoronary imaging.

BACKGROUND: The pathognomonic appearance of multiple radiolucent lumen on angiography is used to diagnose spontaneous coronary artery dissection (SCAD). However, this finding is absent in >70% of SCAD, in which case optical coherence tomography (OCT) or intravascular ultrasound (IVUS) is useful to assess arterial wall integrity. METHODS: We report the angiographic appearance of SCAD that were proven on intracoronary imaging with OCT or IVUS. Our angiographic classification and algorithm for SCAD diagnosis was previously reported. Patients with type 1 SCAD (multiple radiolucent lumen) do not require OCT/IVUS, whereas, it was recommended for those with suspected type 2 (diffuse stenosis) or 3 (mimic atherosclerosis) SCAD. RESULTS: Twenty-two consecutive patients with non-type 1 angiographic SCAD in 25 coronary arteries (22 OCT and 4 IVUS) were studied. Mean age was 52.9 ± 9.9 years, 89.5% were women, and 16/22 (72.7%) had underlying fibromuscular dysplasia. Sixteen SCAD arteries were type 2 SCAD, and nine were type 3. All 25 SCAD arteries had intramural hematoma and intimomedial membrane separation with double lumen on OCT or IVUS. The mean visual angiographic stenosis was 74.6 ± 17.5% (range 40-100%). Dissected segments were long with mean qualitative coronary analysis (QCA) length 45.2 ± 29.2 mm, especially in patients with type 2 SCAD (mean QCA length 58.3 ± 29.0 mm). The mean QCA length in type 3 SCAD lesions was 22.1 ± 5.7 mm. CONCLUSIONS: Intracoronary imaging confirms that SCAD may appear angiographically without multiple radiolucent lumen. Angiographers should be familiar with angiographic SCAD variants to improve SCAD diagnosis, and utilize intracoronary imaging when the diagnosis is uncertain.

One-Year Prospective Follow-up of Women With INOCA and MINOCA at a Canadian Women's Heart Centre.

BACKGROUND: Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women's Heart Centre (WHC). METHODS: Patients with INOCA and MINOCA completed questionnaires on baseline demographics and clinical presentation. At 1-year, frequency of chest pain, quality of life, depression and anxiety symptoms, and cardiovascular outcomes were reported and compared with baseline. RESULTS: A total of 154 women with nonobstructive coronary artery disease were included in this study (112 patients with INOCA and 42 with MINOCA). Median age was 59 years, and the most common referral was for chest pain (94% in INOCA and 66% in MINOCA). At baseline, 64% of patients with INOCA and 43% of patients with MINOCA did not have specific diagnoses. Following investigations in the WHC, 71.4% of patients with INOCA established a new or a changed diagnosis (most common was coronary microvascular dysfunction at 68%), whereas 60% of patients with MINOCA established new or changed diagnoses (the most common of which was coronary vasospasm at 60%). At 1-year, participants had significantly decreased chest pain, improved quality of life, and improved mental health. CONCLUSIONS: A multidisciplinary WHC significantly increases the yield of a specific diagnosis in patients with INOCA and MINOCA. Further, attending a WHC could significantly improve the clinical and psychological outcomes of women with INOCA and MINOCA.

Differences in Demographics and Outcomes Between Men and Women With Spontaneous Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI) that most frequently affects women. The characteristics of men with SCAD are less well described. OBJECTIVES: The aim of this study was to describe the characteristics of men with SCAD. METHODS: We compared baseline demographics, clinical presentation, angiographic findings and cardiovascular outcomes of men and women in the Canadian SCAD Study. Major adverse cardiovascular events (MACE) were composite of death, MI, stroke or transient ischemic attack, heart failure hospitalization, and revascularization. RESULTS: Of 1,173 patients with SCAD, 123 (10.5%) were men. Men with SCAD were younger than women (mean age 49.4 ± 9.6 years vs 52.0 ± 10.6 years; P = 0.01). Men had lower rate of prior MI than women (0.8% vs 7.0%; P = 0.005). Men were less likely to have fibromuscular dysplasia (FMD) (27.8% vs 52.7%; P = 0.001), depression (9.8% vs 20.2%; P = 0.005), emotional stress (35.0% vs 59.3%; P < 0.001), or high score on the Perceived Stress Scale (3.5% vs 11.0%; P = 0.025) but were more likely to report isometric physical stress (40.2% vs 24.0%; P = 0.007). There was no difference in angiographic types of SCAD, but men had more circumflex artery (44.4% vs 30.9%; P = 0.001) and fewer right coronary artery (11.8% vs 21.7%; P = 0.0054) dissections. At median follow-up of 3.0 (IQR: 2.0-3.8) years, men had fewer hospital presentations with chest pain (10.6% vs 24.8%; P < 0.001). There were no differences in in-hospital events or follow-up MACE (7.3% vs 12.7%; P = 0.106). CONCLUSIONS: Ten percent of SCAD patients were men. Men were younger and more likely to have a physical trigger but were less likely to have FMD, depression, or an emotional trigger. Men had less recurrent chest pain but no significant difference in MACE.

Burden of Rare Genetic Variants in Spontaneous Coronary Artery Dissection With High-risk Features.

Importance: The emerging genetic basis of spontaneous coronary artery dissection (SCAD) has been defined as both partially complex and monogenic in some patients, involving variants predominantly in genes known to underlie vascular connective tissue diseases (CTDs). The effect of these genetic influences has not been defined in high-risk SCAD phenotypes, and the identification of a high-risk subgroup of individuals may help to guide clinical genetic evaluations of SCAD. Objective: To identify and quantify the burden of rare genetic variation in individuals with SCAD with high-risk clinical features. Design, Setting, and Participants: Whole-exome sequencing (WES) was performed for subsequent case-control association analyses and individual variant annotation among individuals with high-risk SCAD. Genetic variants were annotated for pathogenicity by in-silico analysis of genes previously defined by sequencing for vascular CTDs and/or SCAD, as well as genes prioritized by genome-wide association study (GWAS) and colocalization of arterial expression quantitative trait loci. Unbiased genome-wide association analysis of the WES data was performed by comparing aggregated variants in individuals with SCAD to healthy matched controls or the Genome Aggregation Database (gnomAD). This study was conducted at a tertiary care center. Individuals in the Canadian SCAD Registry genetics study with a high-risk SCAD phenotype were selected and defined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with family history of arteriopathy. Main Outcomes and Measures: Burden of genetic variants defined by DNA sequencing in individuals with high-risk SCAD. Results: This study included a total of 336 participants (mean [SD] age, 53.0 [9.5] years; 301 female participants [90%]). Variants in vascular CTD genes were identified in 17.0% of individuals (16 of 94) with high-risk SCAD and were enriched (OR, 2.6; 95% CI, 1.6-4.2; P = 7.8 × 10-4) as compared with gnomAD, with leading significant signals in COL3A1 (OR, 13.4; 95% CI, 4.9-36.2; P = 2.8 × 10-4) and Loeys-Dietz syndrome genes (OR, 7.9; 95% CI, 2.9-21.2; P = 2.0 × 10-3). Variants in GWAS-prioritized genes, observed in 6.4% of individuals (6 of 94) with high-risk SCAD, were also enriched (OR, 3.6; 95% CI, 1.6-8.2; P = 7.4 × 10-3). Variants annotated as likely pathogenic or pathogenic occurred in 4 individuals, in the COL3A1, TGFBR2, and ADAMTSL4 genes. Genome-wide aggregated variant testing identified novel associations with peripartum SCAD. Conclusions and Relevance: In this genetic study, approximately 1 in 5 individuals with a high-risk SCAD phenotype harbored a rare genetic variant in genes currently implicated for SCAD. Genetic screening in this subgroup of individuals presenting with SCAD may be considered.

Differences in Revascularization Strategy and Outcomes by Clinical Presentations in Spontaneous Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI). However, the role of revascularization for SCAD according to presentation remains unclear. METHODS: We analyzed patients with SCAD who presented acutely and were participating in the Canadian SCAD Cohort Study. We compared revascularization strategy and clinical outcomes (in-hospital major adverse events and major adverse cardiovascular event [MACE] including recurrent MI at 1-year) in patients with SCAD presenting with ST-elevation MI (STEMI) vs unstable angina or non-STEMI (UA-NSTEMI). RESULTS: Among 750 patients with SCAD (mean 51.7 ± 10.5years; 88.5% were women; median follow-up was 373 days), 234 (31.2%) presented with STEMI. More patients with SCAD-STEMI (27.8%) were treated with revascularization (98.5% percutaneous coronary intervention [PCI]) compared with 8.7% of patients with UA-NSTEMI (93.3% PCI). For patients with SCAD and STEMI, 93.9% were planned procedures vs 71.1% for UA-NSTEMI. Successful or partially successful PCI was 65.5% for STEMI and 76.9% for UA-NSTEMI (P < 0.001). In revascularized patients, 1-year MACE was not different between STEMI and UA-NSTEMI. Revascularization was associated with higher in-hospital major adverse events and its association was more prominent in UA-NSTEMI (STEMI: 26.2% vs 10.7%, P < 0.001; UA-NSTEMI: 37.8% vs 3.6%, P < 0.001). The difference in adverse events according to revascularization diminished over time and was not evident at 1 year. CONCLUSIONS: Despite higher in-hospital events with revascularization in patients with SCAD, and higher revascularization with SCAD-STEMI, 1-year MACE was not different compared with UA-NSTEMI. This is reassuring, as revascularization may be required for ongoing ischemia at the time of initial presentation in STEMI-SCAD, and emphasizes the need for careful patient selection for revascularization in UA-NSTEMI.

Canadian Spontaneous Coronary Artery Dissection Cohort Study: 3-Year Outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-aged women. OBJECTIVES: We aim to define the long-term natural history of SCAD. METHODS: We performed a multicenter, prospective, observational study of patients with nonatherosclerotic SCAD presenting acutely from 22 North American centers. We recorded baseline demographics, in-hospital characteristics, precipitating and predisposing conditions, angiographic features (adjudicated), in-hospital and 3-year major adverse cardiovascular events (MACE). Cox regression multivariable analysis was performed. RESULTS: We prospectively enrolled 750 consecutive patients with SCAD from June 2014 to June 2018. Mean age was 51.7 ± 10.5 years, 88.5% were women (55.0% postmenopausal); 31.3% presented with ST-segment elevation myocardial infarction, and 68.3% with non-ST-segment elevation myocardial infarction. Precipitating emotional stressor was reported in 50.3%, and physical stressor in 28.9%. Predisposing conditions included fibromuscular dysplasia in 42.9% (56.4% in those with complete screening), peripartum state 4.5%, and genetic disorders 1.6%. Most patients were treated conservatively (84.3%); 14.1% underwent percutaneous coronary intervention (PCI), 0.7% coronary artery bypass graft. At 3.0-year median follow-up, mortality was 0.8%, recurrent MI 9.9% (extension of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic dissection 1.9%), with overall MACE 14.0%. Presence of genetic disorders, peripartum SCAD, and extracoronary fibromuscular dysplasia were independent predictors of 3-year MACE. Patients who underwent PCI at index hospitalization had similar postdischarge MACE compared with no PCI. At 3 years, 80.0% remained on aspirin and 73.5% on beta-blockade. CONCLUSIONS: Long-term mortality and de novo recurrent SCAD was low in our contemporary large SCAD cohort that included low revascularization rate and high use of beta-blockade and aspirin. Genetic disorders, extracoronary fibromuscular dysplasia, and peripartum SCAD were independent predictors of long-term MACE.

In-stent restenotic lesions can rupture--a case against plaque sealing.

We present a case of plaque rupture located inside a restenotic stent. Intravascular ultrasound defined a lesion with a minimal lumen area (MLA) of 3.59 cm², plaque burden of 72%, and reference vessel luminal diameter of 4.0 mm with an external elastic membrane lumen cross-section area of 12.6 mm². There was a clearly identified plaque rupture, with a flap-like dissection within the stented segment. Virtual histology intravascular ultrasound confirmed that the adjacent plaque had necrotic core with a thin overlying fibrous cap. The remaining tissue next to the dissection plane was fibrotic. This case illustrates that neointimal hyperplasia may organize into an unstable plaque, with a thin fibrous cap overlying a lipid-rich necrotic core-a so-called virtual histology thin-capped fibroatheroma. As defined in the PROSPECT trial, the in-stent stenotic lesion in our case conformed to the definition of a high-risk plaque-it had an MLA < 4 mm², plaque burden was ≥ 70%, and there was >10% necrotic core. It became unstable and ruptured. The demonstrated findings of this case may sway physicians against sealing hemodynamically nonsignificant unstable plaques.

Coronary Angiographic Manifestations and Outcomes in Spontaneous Coronary Artery Dissection Patients With and Without Fibromuscular Dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is widely recognized as an important predisposing condition for spontaneous coronary artery dissection (SCAD). However, it remains unclear in SCAD patients with coexistent extracoronary FMD whether SCAD can be attributed to coronary FMD. METHODS: We retrospectively analyzed consecutive patients enrolled in our Vancouver SCAD registries between September 2009 and October 2019 who were screened for extracoronary FMD. We reviewed coronary angiograms for manifestations of coronary FMD that were previously described (ie, irregular stenosis, smooth stenosis, dilatation/ectasia, and severe tortuosity). Outcome of interest was major adverse cardiovascular event (MACE). RESULTS: We included 346 SCAD patients, of these, 250 (72.3%) had extracoronary FMD. Patients with FMD were older (54.6 ± 9.5 vs 51.7 ± 9.8 years) and more likely to have prior history of myocardial infarction (7.2% vs 1.0%, P = 0.047) and stroke (4.4% vs 0%, P = 0.081) compared with non-FMD patients. On coronary angiography, severe tortuosity was more prevalent in patients with extracoronary FMD (58.4% vs 36.5%, P < 0.001). Rates of irregular stenosis, smooth stenosis, and dilatation/ectasia were numerically higher in patients with extracoronary FMD, but differences were not significantly different. The rate of MACE at median follow-up of 807 (interquartile range, 392-1096) days was not different between groups (19.6% vs 15.6%; non-FMD as a reference: hazard ratio 1.44; 95% confidence interval, 0.76-2.71, P = 0.261). CONCLUSION: SCAD patients with extracoronary FMD were more likely to have coronary FMD manifestations on angiogram, especially severely tortuous vessels, compared with those without extracoronary FMD, with similar clinical outcomes. This may suggest that SCAD can occur at sites of pre-existent subclinical coronary FMD.

Cardiac CT angiography after percutaneous left atrial appendage closure: early versus delayed scanning after contrast administration.

PURPOSE: Cardiac computed tomography angiography (CCTA) is increasingly used for device surveillance after left atrial appendage closure (LAAC). While CT protocols with delayed scans are useful to diagnose thrombus in the LAA, an optimal protocol for post-procedural CCTA has not been established. Therefore, we assessed the role of delayed versus early scans for device surveillance. METHODS: We retrospectively reviewed patients who underwent LAAC at Vancouver General Hospital who had follow-up CCTAs using standard (early) and delayed scans. Scans were performed on Toshiba 320-detector (Aquilion ONE). Image quality was interpreted by 2 independent observers for anatomy, LAA contrast patency, and device-related thrombus (DRT) using VitreaWorkstationTM. A Likert scale of 1-5 was used (1= poor quality, 5= excellent) for assessment. RESULTS: We included 27 consecutive LAAC patients (9 Amplatzer, 18 WATCHMAN) with mean age 76.0±7.7 years, mean CHADS2 score 2.8±1.3, CHA2DS2-VASc score 4.4±1.6 and HAS-BLED score 3.4±1.0. Subjective quality assessments by both reviewers favored early scans for assessment of anatomy (reviewer 1: 4.63±0.63 [early] vs. 1.74±0.71 [delayed]; reviewer 2: 4.63±0.63 [early] vs. 1.89±0.64 [delayed]) and DRT (reviewer 1: 4.78±0.42 [early] vs. 3.11±1.16 [delayed]; reviewer 2: 4.70±0.47 [early] vs. 3.04±1.29 [delayed]). Inter-rater variability showed good correlation between reviewers (intraclass correlation 0.61-0.95). Mean LAA/LA attenuation ratios were significantly different between scans, with larger mean percent reduction of contrast opacification from LA to LAA in the early scans (57.0±36.6% reduction for early vs. 29.1±30.8% for delayed; p < 0.001) CONCLUSION: For CT device surveillance post-LAAC early phase imaging provides superior image quality objectively and subjectively compared with delayed scanning.

Coronary Flow Reserve in Patients With Prior Spontaneous Coronary Artery Dissection and Recurrent Angina.

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 <2.5 was defined as diagnostic of coronary microvascular dysfunction. An abnormal index of microcirculatory resistance was defined as >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 <2.5 and 13 (76.5%) had an index of microcirculatory resistance >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.

In-hospital and long-term outcomes among patients with spontaneous coronary artery dissection presenting with ventricular tachycardia/fibrillation.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in young to middle-age women. Ventricular tachycardia/ventricular fibrillation (VT/VF) may complicate acute SCAD presentations, and the long-term outcomes are unknown. OBJECTIVE: The purpose of this study was to report the outcomes of SCAD patients presenting with VT/VF. METHODS: We analyzed our prospective Canadian SCAD registries for patients presenting with VT/VF during index hospitalization. Long-term outcomes including VT/VF and cardiac arrest were collected. Univariate and multivariable analyses were performed to identify predictors of VT/VF at follow-up. RESULTS: Among 1056 consecutive SCAD patients, 84 (8.0%) presented with VT/VF, and 8 underwent implantable cardioverter-defibrillator (ICD) insertion. Patients with VT/VF during index hospitalization were younger (49.3 vs 52.0 years; P = .019) and were more likely to have ST-elevation MI, lower left ventricular ejection fraction (LVEF), and left main dissection (all P <.001). Initial VT/VF was associated with in-hospital events, including recurrent MI, unplanned revascularization, heart failure, ICD insertion, and in-hospital death (all P <.05). At mean follow-up of 4.8 ± 3.3 years, 8 patients suffered VT/VF (time to event 5.2 ± 6.2 years); 5 of 8 patients had VT/VF on initial SCAD presentation, and 1 of 8 had undergone ICD insertion. Predictors of VT/VF during follow-up included LVEF <50%, LVEF <35%, peripartum SCAD, unplanned revascularization, repeat MI, heart failure, and initial VT/VF. Multivariable analysis showed initial VT/VF (odds ratio [OR] 9.5; 95% confidence interval [CI] 2.0-44; P = .004) and LVEF <50% (OR 12.9; 95% CI 1.5-111; P = .019) were independent predictors of VT/VF at follow-up. CONCLUSION: SCAD patients presenting with VT/VF were at greater risk for in-hospital events and recurrent VF/VT at follow-up. Both VT/VF and LVEF <50% were independent predictors of subsequent VT/VF.

Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction.

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction (MI), typically in young women. We undertook a genome-wide association study of SCAD (Ncases = 270/Ncontrols = 5,263) and identified and replicated an association of rs12740679 at chromosome 1q21.2 (Pdiscovery+replication = 2.19 × 10-12, OR = 1.8) influencing ADAMTSL4 expression. Meta-analysis of discovery and replication samples identified associations with P < 5 × 10-8 at chromosome 6p24.1 in PHACTR1, chromosome 12q13.3 in LRP1, and in females-only, at chromosome 21q22.11 near LINC00310. A polygenic risk score for SCAD was associated with (1) higher risk of SCAD in individuals with fibromuscular dysplasia (P = 0.021, OR = 1.82 [95% CI: 1.09-3.02]) and (2) lower risk of atherosclerotic coronary artery disease and MI in the UK Biobank (P = 1.28 × 10-17, HR = 0.91 [95% CI :0.89-0.93], for MI) and Million Veteran Program (P = 9.33 × 10-36, OR = 0.95 [95% CI: 0.94-0.96], for CAD; P = 3.35 × 10-6, OR = 0.96 [95% CI: 0.95-0.98] for MI). Here we report that SCAD-related MI and atherosclerotic MI exist at opposite ends of a genetic risk spectrum, inciting MI with disparate underlying vascular biology.

Natural History of Spontaneous Coronary Artery Dissection With Spontaneous Angiographic Healing.

OBJECTIVES: Given the uncertainty regarding the degree and prevalence of spontaneous healing following spontaneous coronary artery dissection (SCAD), the aim of this study was to assess the angiographic characteristics of the dissected segments in a large cohort of patients with SCAD who underwent subsequent repeat coronary angiography. BACKGROUND: SCAD is an uncommon yet important cause of myocardial infarction in women. Very little is known about the characteristics of healing of dissected arteries. METHODS: Patients with nonatherosclerotic SCAD followed prospectively at Vancouver General Hospital who underwent repeat angiography were included in this study. Those who underwent percutaneous coronary intervention for SCAD were excluded. Baseline patient demographics and in-hospital and long-term cardiovascular events were recorded. Angiographic characteristics of the SCAD artery at index and repeat angiography were assessed by 2 experienced angiographers. Criteria for angiographic healing were as follows: 1) improvement of stenosis severity from index event; 2) residual stenosis <50%; and 3) TIMI (Thrombolysis In Myocardial Infarction) flow grade 3. RESULTS: One hundred fifty-six patients with 182 noncontiguous SCAD lesions were included. The mean age was 51.5 ± 8.7 years, 88.5% were women, 83.3% were Caucasian, and 75.6% had fibromuscular dysplasia. All patients presented with myocardial infarction. At index angiography, type 2 SCAD was most commonly observed, in 126 of 182 lesions (69.2%); TIMI flow grade <3 was present in 85 of 182 (46.7%); and median lesion stenosis was 79.0% (interquartile range: 56.0% to 100%). Median time to repeat angiography was 154 days (interquartile range: 70 to 604 days), with median residual lesion stenosis improving to 25.5% (interquartile range: 12.0 to 38.8 days), and TIMI flow grade <3 observed in 10 of 182 lesions (5.5%). Angiographic healing occurred in 157 of 182 lesions (86.3%). Of repeat angiography performed ≥30 days post-SCAD, 152 of 160 (95%) showed spontaneous angiographic healing. CONCLUSIONS: The majority of coronary arteries affected by SCAD heal spontaneously on repeat angiography, with apparent time dependency, with the vast majority having complete healing after 30 days from the SCAD event.