Abstract Spontaneous coronary artery dissection (SCAD) is gaining recognition as an important cause of myocardial infarction, especially in young women. There has been a surge in the diagnosis of ...SCAD in recent years, presumably due to an increased use of coronary angiography, and the clinical availability and application of high-resolution intracoronary imaging. The improved recognition and diagnosis, together with increased publications and attention through social media, have considerably raised awareness of this condition, which was once believed to be very rare. Recent publications of moderate to large contemporary case series have helped elucidate the early natural history, presenting characteristics (clinical and angiographic), underlying etiology, management, and cardiovascular outcomes with this condition, thus providing observations and important clinical insights of value to clinicians managing this challenging and perplexing patient cohort. The aim of our review is to provide a comprehensive contemporary update of SCAD to aid health care professionals in managing these patients in both the acute and chronic settings.
There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction, particularly women. We sought to determine the ...mechanism(s) of myocardial infarction in this setting using multiple imaging techniques.
Women with myocardial infarction were enrolled prospectively, before angiography, if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound was performed during angiography; cardiac magnetic resonance imaging was performed within 1 week. Fifty women (age, 57±13 years) had median peak troponin of 1.60 ng/mL; 11 had ST-segment elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16 of 42 patients (38%) undergoing intravascular ultrasound. There were abnormal myocardial cardiac magnetic resonance imaging findings in 26 of 44 patients (59%) undergoing cardiac magnetic resonance imaging, late gadolinium enhancement (LGE) in 17 patients, and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Nonischemic LGE patterns (midmyocardial/subepicardial) were also observed. Although LGE was infrequent with plaque disruption, T2 signal hyperintensity was common with plaque disruption.
Plaque rupture and ulceration are common in women with myocardial infarction without angiographically demonstrable obstructive coronary artery disease. In addition, LGE is common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provide complementary mechanistic insights into female myocardial infarction patients without obstructive coronary artery disease and may be useful in identifying potential causes and therapies. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00798122.
Spontaneous coronary artery dissection (SCAD) is underdiagnosed and an important cause of myocardial infarction (MI), especially in young women. Long-term cardiovascular outcomes, including recurrent ...SCAD, are inadequately reported.
This study sought to describe the acute and long-term cardiovascular outcomes and assess the predictors of recurrent SCAD.
Nonatherosclerotic SCAD patients were prospectively followed at Vancouver General Hospital systematically to ascertain baseline, predisposing and precipitating stressors, angiographic features, revascularization, use of medication, and in-hospital and long-term cardiovascular events. Clinical predictors for recurrent de novo SCAD were tested using univariate and multivariate Cox regression models.
The authors prospectively followed 327 SCAD patients. Average age was 52.5 ± 9.6 years, and 90.5% were women (56.9% postmenopausal). All presented with MI; 25.7% had ST-segment elevation MI, 74.3% had non-ST-segment elevation MI, and 8.9% had ventricular tachycardia/ventricular fibrillation. Precipitating emotional stressors were reported in 48.3% and physical stressors in 28.1%. Fibromuscular dysplasia was present in 62.7%, connective tissue disorder in 4.9%, and systemic inflammatory disease in 11.9%. The majority (83.1%) were initially treated medically, with only 16.5% or 2.2% undergoing in-hospital percutaneous coronary intervention or coronary artery bypass graft surgery, respectively. The majority of SCAD patients were taking aspirin and beta-blocker therapy at discharge and at follow-up. Median hospital stay was 3.0 days, and the overall major adverse event rate was 7.3%. Median long-term follow-up was 3.1 years, and overall major adverse cardiac event rate was 19.9% (death rate: 1.2%; recurrent MI: 16.8%; stroke/transient ischemic attack: 1.2%; revascularization: 5.8%). Recurrent SCAD occurred in 10.4% of patients. In multivariate modeling, only hypertension increased (hazard ratio: 2.46; p = 0.011) and beta-blocker use diminished (hazard ratio: 0.36; p = 0.004) recurrent SCAD.
In our large prospectively followed SCAD cohort, long-term cardiovascular events were common. Hypertension increased the risk of recurrent SCAD, whereas beta-blocker therapy appeared to be protective.
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.
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%.
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.
Abstract Background Nonatherosclerotic coronary artery disease (NACAD) is an important cause of myocardial infarction (MI) in young women but is often missed on coronary angiography, especially ...spontaneous coronary artery dissection (SCAD). The prevalence of NACAD in young women has not been described. Methods We retrospectively reviewed all coronary angiograms of women aged 50 years and younger at Vancouver General Hospital from December 1, 2009 to November 30, 2011. The angiograms were reviewed by 2 experienced interventional cardiologists, and reported as normal (<30% stenosis), atherosclerotic coronary artery disease (ACAD), or NACAD. NACAD was further characterized as SCAD, coronary fibromuscular dysplasia (FMD), ectasia, vasculitis, embolism, congenital anomaly, or unclear etiology. Results Of 7605 coronary angiograms performed, 177 were done in women aged 50 years and younger. The mean age was 45.4 ± 4.9 (range, 31-50) years, 76 of 177 (42.9%) presented with acute coronary syndrome, and 66 were troponin-positive. Ninety-seven (54.8%) women had normal arteries, 54 (30.5%) had ACAD, 23 (13.0%) had NACAD, and 3 (1.7%) had unclear etiology. Of those with NACAD, SCAD was observed in 16 (all troponin-positive and 13 of 16 had noncoronary FMD), and 2 had irregular beading suspicious of coronary FMD. Coronary vasculitis was suspected in 2, and 5 had coronary ectasia. Among women with MI (66/177), 19 (28.8%) had normal arteries (3 Takotsubo cardiomyopathy), 24 (36.4%) had ACAD, 20 (30.3%) had NACAD, 16 (24.2%) had SCAD, and 3 had unclear etiology. Conclusions NACAD was not rare among young women (aged 50 years and younger) undergoing coronary angiography and was an important cause of MI, accounting for 30%. SCAD was the most commonly encountered NACAD in young women, causing 24% of MIs.
We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection. Angiographic manifestations of coronary FMD aside from dissection were ...considered rare. However, we observed several coronary FMD angiographic abnormalities with corresponding optical coherence tomography abnormalities.
Baseline demographics and imaging of patients with suspected coronary FMD at Vancouver General Hospital were reviewed. Presence of multifocal (string-of-beads) extracoronary FMD was confirmed by 2 specialists. In these patients, coronary angiographic findings (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for irregular stenosis, that is, stenosis with irregular borders in a focal or diffuse pattern with/without systolic accentuation; smooth stenosis, diffuse or focal; segmental dilatation/ectasia; and tortuosity. Optical coherence tomography was performed in a subset of patients. Of 32 patients with extracoronary FMD and suspected coronary involvement, 28 were women (88%), and their mean age was 59.4±9.9 years. Nineteen presented with myocardial infarction (13 caused by spontaneous coronary artery dissection), and 13 had stable symptoms. The observed coronary angiographic abnormalities included tortuosity in all cases (91% were moderate to severe), irregular stenosis in 59%, smooth stenosis in 19%, and segmental dilatation/ectasia in 56%. Fifteen patients had optical coherence tomography of the abnormal segments showing abnormalities, including multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with thickening/accumulation of varied reflectivities, macrophage infiltration, loss/duplication of elastic membranes, and cavitation.
This is the first case series describing findings suggestive of angiographic and intracoronary manifestations of coronary FMD. Future studies should prospectively review these features in patients with extracoronary FMD.
Lipoprotein(a) is an atherogenic low-density lipoprotein-like particle and circulating levels are largely determined by genetics. Patients with familial hypercholesterolemia (FH) have elevated ...lipoprotein(a); however, it remains unclear why.
This study compared the levels of lipoprotein(a) and associated genetic factors between individuals that were ascertained for FH clinically versus genetically.
We investigated causes of elevated lipoprotein(a) in individuals with clinically diagnosed FH (FH cohort, n = 391) and in individuals with genetically diagnosed FH from the general population (UK Biobank; n = 37,486).
Patients in the FH cohort had significantly greater lipoprotein(a) levels than either the general population or non-FH dyslipidemic patients. This was accounted for by increased frequency of the rs10455872-G LPA risk allele (15.1% vs. 8.8%; p < 0.05). However, within the FH cohort, lipoprotein(a) levels did not differ based on the presence or absence of an FH-causing variant (means = 1.43 log mg/dl vs. 1.42 log mg/dl; p = 0.97). Lipoprotein(a) levels were also not statistically different between individuals with and without an FH-causing variant in the UK Biobank cohort, which represents a population sample not biased to cardiovascular ascertainment (n = 221 vs. 37,486). We performed a phenome-wide association study between LPA genotypes and 19,202 phenotypes to demonstrate that elevated lipoprotein(a) is associated with increased low-density lipoprotein cholesterol, a family history of cardiovascular disease, premature coronary artery disease, and a diagnosis of FH.
These results suggest that FH does not cause elevated lipoprotein(a), but that elevated lipoprotein(a) increases the likelihood that an individual with genetic FH will be clinically recognized.
A pathogenic variant in LDLR, APOB, or PCSK9 can be identified in 30% to 80% of patients with clinically-diagnosed familial hypercholesterolemia (FH). Alternatively, ∼20% of clinical FH is thought to ...have a polygenic cause. The cardiovascular disease (CVD) risk associated with polygenic versus monogenic FH is unclear.
This study evaluated the effect of monogenic and polygenic causes of FH on premature (age <55 years) CVD events in patients with clinically diagnosed FH.
Targeted sequencing of genes known to cause FH as well as common genetic variants was performed to calculate polygenic scores in patients with “possible,” “probable,” or “definite” FH, according to Dutch Lipid Clinic Network Criteria (n = 626). Patients with a polygenic score ≥80th percentile were considered to have polygenic FH. We examined the risk of unstable angina, myocardial infarction, coronary revascularization, or stoke.
A monogenic cause of FH was associated with significantly greater risk of CVD (adjusted hazard ratio: 1.96; 95% confidence interval: 1.24 to 3.12; p = 0.004), whereas the risk of CVD in patients with polygenic FH was not significantly different compared with patients in whom no genetic cause of FH was identified. However, the presence of an elevated low-density lipoprotein cholesterol (LDL-C) polygenic risk score further increased CVD risk in patients with monogenic FH (adjusted hazard ratio: 3.06; 95% confidence interval: 1.56 to 5.99; p = 0.001).
Patients with monogenic FH and superimposed elevated LDL-C polygenic risk scores have the greatest risk of premature CVD. Genetic testing for FH provides important prognostic information that is independent of LDL-C levels.
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Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, fractional ...flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFR(CT)) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date.
To assess the diagnostic performance of FFR(CT) plus CT for diagnosis of hemodynamically significant coronary stenosis.
Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR(CT) between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFR(CT) were interpreted in blinded fashion by independent core laboratories. Accuracy of FFR(CT) plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFR(CT) of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA.
The primary study outcome assessed whether FFR(CT) plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%.
Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve AUC, 0.68; 95% CI, 0.62-0.74), FFR(CT) was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001).
Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFR(CT) plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.
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