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2.
Can J Cardiol ; 38(10): 1600-1610, 2022 10.
Article in English | MEDLINE | ID: mdl-36202592

ABSTRACT

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.


Subject(s)
Coronary Artery Disease , Canada/epidemiology , Chest Pain/diagnosis , Chest Pain/epidemiology , Chest Pain/etiology , Coronary Angiography , Female , Follow-Up Studies , Humans , MINOCA , Middle Aged , Prospective Studies , Quality of Life
3.
JACC Cardiovasc Interv ; 15(20): 2052-2061, 2022 10 24.
Article in English | MEDLINE | ID: mdl-36265936

ABSTRACT

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.


Subject(s)
Coronary Vessel Anomalies , Fibromuscular Dysplasia , Myocardial Infarction , Vascular Diseases , Humans , Male , Female , Adult , Middle Aged , Coronary Vessels , Coronary Angiography/adverse effects , Canada/epidemiology , Treatment Outcome , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessel Anomalies/epidemiology , Coronary Vessel Anomalies/therapy , Vascular Diseases/diagnostic imaging , Vascular Diseases/epidemiology , Vascular Diseases/therapy , Fibromuscular Dysplasia/complications , Myocardial Infarction/etiology , Chest Pain/complications , Demography
4.
J Am Coll Cardiol ; 80(17): 1585-1597, 2022 10 25.
Article in English | MEDLINE | ID: mdl-36265953

ABSTRACT

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.


Subject(s)
Fibromuscular Dysplasia , Myocardial Infarction , Non-ST Elevated Myocardial Infarction , Humans , Middle Aged , Female , Adult , Male , Fibromuscular Dysplasia/complications , Cohort Studies , Coronary Vessels , Prospective Studies , Aftercare , Coronary Angiography/adverse effects , Canada , Patient Discharge , Myocardial Infarction/etiology , Non-ST Elevated Myocardial Infarction/complications , Aspirin
5.
JAMA Cardiol ; 7(10): 1045-1055, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36103205

ABSTRACT

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.


Subject(s)
Coronary Vessels , Genome-Wide Association Study , Canada , Coronary Vessel Anomalies , Female , Genetic Testing , Humans , Receptor, Transforming Growth Factor-beta Type II , Vascular Diseases/congenital
6.
JAMA ; 328(6): 554-562, 2022 08 09.
Article in English | MEDLINE | ID: mdl-35943473

ABSTRACT

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.


Subject(s)
Aspirin , Coronary Artery Bypass , Platelet Aggregation Inhibitors , Saphenous Vein , Ticagrelor , Aged , Aspirin/adverse effects , Aspirin/therapeutic use , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/methods , Female , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/prevention & control , Hemorrhage/chemically induced , Hemorrhage/etiology , Humans , Male , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Saphenous Vein/transplantation , Ticagrelor/adverse effects , Ticagrelor/therapeutic use , Treatment Outcome
7.
Can J Cardiol ; 38(12): 1935-1943, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35850384

ABSTRACT

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.


Subject(s)
Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Female , Male , Percutaneous Coronary Intervention/methods , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Cohort Studies , Canada/epidemiology , Angina, Unstable/diagnosis , Angina, Unstable/etiology , Angina, Unstable/surgery , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/etiology , ST Elevation Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/etiology , Treatment Outcome
8.
Diagn Interv Radiol ; 27(6): 703-709, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34792023

ABSTRACT

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.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Aged , Aged, 80 and over , Atrial Appendage/diagnostic imaging , Atrial Appendage/surgery , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Cardiac Catheterization , Computed Tomography Angiography , Humans , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
9.
Can J Cardiol ; 37(11): 1725-1732, 2021 11.
Article in English | MEDLINE | ID: mdl-34478855

ABSTRACT

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.


Subject(s)
Coronary Angiography/methods , Coronary Vessel Anomalies/diagnosis , Coronary Vessels/diagnostic imaging , Fibromuscular Dysplasia/diagnosis , Vascular Diseases/congenital , Coronary Vessel Anomalies/complications , Female , Fibromuscular Dysplasia/complications , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Vascular Diseases/complications , Vascular Diseases/diagnosis
10.
J Interv Cardiol ; 2021: 6686230, 2021.
Article in English | MEDLINE | ID: mdl-34104121

ABSTRACT

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.


Subject(s)
Coronary Vessel Anomalies/surgery , Long Term Adverse Effects , Percutaneous Coronary Intervention , Postoperative Complications , Stents , Vascular Diseases/congenital , Coronary Vessel Anomalies/diagnosis , Female , Humans , Long Term Adverse Effects/diagnosis , Long Term Adverse Effects/epidemiology , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/methods , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Risk Adjustment , Risk Assessment , Risk Factors , Sex Factors , Treatment Outcome , Vascular Diseases/diagnosis , Vascular Diseases/surgery
13.
Nat Commun ; 11(1): 4432, 2020 09 04.
Article in English | MEDLINE | ID: mdl-32887874

ABSTRACT

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.


Subject(s)
Coronary Vessel Anomalies/genetics , Genes, Neoplasm , Myocardial Infarction/genetics , Vascular Diseases/congenital , ADAMTS Proteins/genetics , Carotid Artery Diseases/complications , Carotid Artery Diseases/genetics , Chromosomes/genetics , Cohort Studies , Coronary Artery Disease/genetics , Female , Fibromuscular Dysplasia/complications , Fibromuscular Dysplasia/genetics , Genome-Wide Association Study , Humans , Low Density Lipoprotein Receptor-Related Protein-1/genetics , Male , Meta-Analysis as Topic , Microfilament Proteins/genetics , Risk Factors , Vascular Diseases/genetics
14.
J Am Heart Assoc ; 9(16): e015834, 2020 08 18.
Article in English | MEDLINE | ID: mdl-32755255

ABSTRACT

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.


Subject(s)
Angina Pectoris/etiology , Coronary Circulation/physiology , Coronary Vessel Anomalies/physiopathology , Fibromuscular Dysplasia/complications , Microcirculation/physiology , Vascular Diseases/congenital , Female , Fibromuscular Dysplasia/diagnosis , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Recurrence , Stents , Vascular Diseases/physiopathology , Vascular Resistance/physiology
16.
Heart Rhythm ; 17(11): 1864-1869, 2020 11.
Article in English | MEDLINE | ID: mdl-32590153

ABSTRACT

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.


Subject(s)
Coronary Vessel Anomalies/complications , Stroke Volume/physiology , Vascular Diseases/congenital , Ventricular Fibrillation/etiology , Ventricular Function, Left/physiology , Canada/epidemiology , Coronary Vessel Anomalies/physiopathology , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Time Factors , Vascular Diseases/complications , Vascular Diseases/physiopathology , Ventricular Fibrillation/mortality , Ventricular Fibrillation/physiopathology
17.
Am J Ther ; 27(2): e151-e158, 2020.
Article in English | MEDLINE | ID: mdl-29746286

ABSTRACT

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.


Subject(s)
Microvascular Angina/drug therapy , Ranolazine/therapeutic use , Sodium Channel Blockers/therapeutic use , Aged , Cohort Studies , Electrocardiography , Female , Humans , Male , Middle Aged , Patient Satisfaction , Quality of Life , Treatment Outcome
19.
JACC Cardiovasc Interv ; 12(6): 518-527, 2019 03 25.
Article in English | MEDLINE | ID: mdl-30826233

ABSTRACT

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.


Subject(s)
Coronary Angiography , Coronary Stenosis/diagnostic imaging , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessels/diagnostic imaging , Vascular Diseases/congenital , Wound Healing , Adult , British Columbia , Coronary Stenosis/physiopathology , Coronary Vessel Anomalies/physiopathology , Coronary Vessels/physiopathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Time Factors , Vascular Diseases/diagnostic imaging , Vascular Diseases/physiopathology
20.
J Cardiovasc Comput Tomogr ; 13(2): 86-91, 2019.
Article in English | MEDLINE | ID: mdl-30718182

ABSTRACT

BACKGROUND: Myocardial CT perfusion imaging with dual energy (DE-CTP) can produce myocardial iodine perfusion maps. This study evaluated the accuracy of first pass myocardial iodine concentration in DE-CTP compared to CT derived dynamic myocardial blood flow (MBF) to determine regional myocardial ischemia in an animal model of coronary stenosis using invasive Fractional Flow Reserve (FFR). METHODS: Seven anaesthetised pigs (mean weight 51 ±â€¯4 kg) had a graded coronary artery stenosis produced in six vessels (plus one control animal) using a methacrylate plug with FFR recorded in the target artery (ischemia = FFR<0.80). During adenosine vasodilation, dynamic myocardial CTP and DE-CTP imaging was performed. Using vendor supplied applications, matching regions of interest (ROIs) were drawn in myocardial segments supplied by the target coronary artery to compare the two techniques. RESULTS: FFR correlated strongly to MBF (r = 0.81) and modestly to myocardial iodine concentration (r = 0.65) and myocardial CT attenuation (r = 0.62) (p < 0.0001 each). The correlation to FFR was stronger using relative ratios (absolute value/reference value of normal segments) than absolute values for MBF (r = 0.86), myocardial iodine concentration (r = 0.80) and CT number (r = 0.79) (p < 0.0001 each). Comparing normal and ischaemic territories there were significant differences in MBF (96 ±â€¯14 vs. 27 ±â€¯18 ml/100 ml of tissue/min, p < 0.0001), myocardial iodine concentration (3.5 ±â€¯1 vs. 1.0 ±â€¯0.7 mg/ml, p < 0.0001) and myocardial CT number (89 ±â€¯9 vs. 73 ±â€¯14 HU, p = 0.002). Myocardial iodine concentration had 91% sensitivity and 98% specificity for detecting FFR <0.8. CONCLUSION: Quantified myocardial iodine content from first pass DE-CTP correlates with CT derived myocardial blood flow and FFR and accurately discriminates ischemic territories in a porcine model. The accuracy and utility of myocardial iodine content in DE-CTP warrants further investigation in a clinical population with FFR as a reference standard.


Subject(s)
Contrast Media/metabolism , Coronary Stenosis/diagnostic imaging , Fractional Flow Reserve, Myocardial , Iodine/metabolism , Myocardial Perfusion Imaging/methods , Myocardium/metabolism , Tomography, X-Ray Computed , Adenosine/administration & dosage , Animals , Contrast Media/administration & dosage , Coronary Stenosis/metabolism , Coronary Stenosis/physiopathology , Disease Models, Animal , Female , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Reproducibility of Results , Severity of Illness Index , Sus scrofa , Vasodilator Agents/administration & dosage
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