Intravascular Imaging in the Diagnosis and Management of Patients With Suspected Intracoronary Pathologies: A CJC White Paper.

Intravascular imaging has become an integral part of the diagnostic and management strategies for intracoronary pathologies. In this White Paper we summarize current evidence and its implications on the use of intravascular imaging in interventional cardiology practice. The areas addressed are planning and optimization of percutaneous coronary intervention, management of stent failure, and evaluation of ambiguous coronary lesions and myocardial infarction with nonobstructive coronary disease. The findings presented followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in an expert consensus process that involved a diverse writing group vetted by a review group. Expert consensus was achieved around 9 statements. Use of intravascular imaging in guiding percutaneous revascularization is supported by high-quality evidence, particularly for lesions with increased risk of recurrent events or stent failure. Specific considerations for intravascular imaging guidance of intervention in left main lesions, chronic occlusion lesions, and in patients at high risk of contrast nephropathy are explored. Use of intravascular imaging to identify pathologies associated with stent failure and guide repeat intervention, resolve ambiguities in lesion assessment, and establish diagnoses in patients who present with myocardial infarction with nonobstructive coronary disease is supported by moderate- to low-quality evidence. Each topic is accompanied by clinical pointers to aid the practicing interventional cardiologist in implementation of the White Paper findings. The findings presented in this White Paper will help to guide the use of intravascular imaging toward situations in which the balance of efficacy, safety, and cost are most optimal.

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.

Initial Findings From the North American COVID-19 Myocardial Infarction Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). OBJECTIVES: The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. METHODS: A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. RESULTS: As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). CONCLUSIONS: COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

Carotid artery visualization during anterior skull base surgery: a novel protocol for neuronavigation.

Detailed knowledge of the vascular anatomy of the anterior skull base is critical to successful surgery in this area. Whereas conventional neuronavigational approaches combine MRI (+/- contrast) for tumor visualization and CT (+/- C) for bony and vascular anatomy, we describe the Canadian and Austrian experiences using a novel protocol integrating MR angiography (MRA) into surgical neuronavigation to provide superior visualization of the carotid arteries. The pre-operative imaging protocol employs a T1-weighted, 3D fast spoiled gradient echo MRI (+/- C) for soft tissue anatomy, a plain CT for bony anatomy, and a 3D time-of-flight MR angiography for carotid anatomy. The series are imported into the Medtronic StealthStation((R)) TREON((R)) Treatment Guidance System; during intra-operative neuronavigation, each series (MRI, CT, MRA) can be viewed individually, or layered and viewed as a composite image. Our protocol has important advantages. First, it provides detailed tissue, tumor, vascular and bony anatomy. Second, a contrast CT is not necessary; this is important, as numerous reports have highlighted the nephrotoxic nature of radiographic contrast material. Third, visualization of the carotid system is superior than can be obtained from CT angiography. We use this unique imaging protocol routinely for our endoscopic transsphenoidal surgeries to provide superior visualization of the carotid arteries during anterior skull base surgery.

Lithium and valproate and their possible effects on themyo-inositol second messenger system in healthy volunteers and bipolar patients.

Over 25 years ago it was suggested that the mechanism by which lithium was clinically effective may be due to a stabilizing effect on the phosphoinositol second messenger system (PI-cycle), which has multiple effects within cells. It was proposed that lithium, which is an inhibitor of one of the key enzymes in the PI-cycle, acted to lower myo-inositol concentrations; termed the 'inositol-depletion hypothesis'. Initial animal evidence supported this hypothesis, and also suggested that it was possible that sodium valproate could affect the PI-cycle. Since the first magnetic resonance studies in this area in the early 1990s many studies have examined various aspects of this hypothesis in both healthy volunteers and patients utilizing magnetic resonance spectroscopy (MRS). The present review considers research in this area and concludes that, despite initial promise, current evidence suggests that it is unlikely that either lithium or valproate produce clinically relevant changes in myo-inositol concentrations or the PI-cycle. These findings do not suggest that lithium-induced changes in the PI-cycle are the primary mechanism by which lithium or valproate exert their beneficial clinical effects in bipolar disorder. Nonetheless, given the current technical and clinical limitations of the literature to date, this conclusion cannot be considered completely definitive.

Acute dextro-amphetamine administration does not alter brain myo-inositol levels in humans and animals: MRS investigations at 3 and 18.8 T.

The pathophysiological underpinnings of bipolar disorder are not fully understood. However, they may be due in part to changes in the phosphatidylinositol second messenger system (PI-cycle) generally, or changes in myo-inositol concentrations more specifically. Dextro-amphetamine has been used as a model for mania in several human studies as it causes similar subjective and physiological symptoms. We wanted to determine if dextro-amphetamine altered myo-inositol concentrations in vivo as it would clearly define a mechanism linking putative changes in the PI-cycle to the subjective psychological changes seen with dextro-amphetamine administration. Fifteen healthy human volunteers received a baseline scan, followed by second scan 75 min after receiving a 25 mg oral dose of dextro-amphetamine. Stimulated echo proton magnetic resonance spectroscopy (MRS) scans were preformed at 3.0 Tesla (T) in the dorsal medial prefrontal cortex (DMPFC). Metabolite data were adjusted for tissue composition and analyzed using LCModel. Twelve adult male rats were treated acutely with a 5-mg/kg intraperitoneal dose of dextro-amphetamine. After 1 h rats were decapitated and the brains were rapidly removed and frozen until dissection. Rat brains were dissected into frontal, temporal, and occipital cortical areas, as well as hippocampus. Tissue was analyzed using a Varian 18.8 T spectrometer. Metabolites were identified and quantified using Chenomx Profiler software. The main finding in the present study was that myo-inositol concentrations in the DMPFC of human volunteers and in the four rat brain regions were not altered by acute dextro-amphetamine. While it remains possible that the PI-cycle may be involved in the pathophysiology of bipolar disorder, it is not likely that the subjective and physiological of dextro-amphetamine are mediated, directly or indirectly, via alternations in myo-inositol concentrations.

Novel use of cutting balloon to manage compressive subintimal hematoma during left main stenting in a patient with spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a common cause of acute coronary syndrome particularly in younger women. Good outcomes with conservative management are generally expected. However, there is uncertainty of how to manage symptomatic or unstable patients. Percutaneous angioplasty may propagate the subintimal hematoma compromising coronary blood flow. Cutting balloon angioplasty can relieve the compressive effects of a propagated subintimal hematoma in SCAD.

Unlike lithium, anticonvulsants and antidepressants do not alter rat brain myo-inositol.

Lithium is the first-line in bipolar disorder treatment. Lithium's clinical efficacy might be due to its inhibition of myo-inositol turnover in the phosphatidylinositol second messenger system. This study aimed to determine whether this action can extend to antidepressants and anticonvulsants also used to treat bipolar symptoms. Male rats were treated for 2 weeks with an intraperitoneal injection of phenelzine, fluoxetine, desipramine, carbamazepine, lamotrigine, sodium valproate or vehicle. Brains were dissected and myo-inositol concentrations were analyzed using high-field nuclear magnetic resonance spectroscopy at 18.8 T and quantified using Chenomx Profiler software. Brain regions assessed included the prefrontal, temporal and occipital cortical areas as well as the hippocampus. The main finding is that contrary to lithium, the anticonvulsants and antidepressants do not alter brain myo-inositol concentration. This suggests that these agents might work via a mechanism that is not centered on changes in myo-inositol concentration.

Quality of life following coronary artery bypass graft surgery vs. percutaneous coronary intervention in diabetics with multivessel disease: a five-year registry study.

Aims: The aim of this study is to investigate the long-term relationship between revascularization technique and health status in diabetics with multivessel disease. Methods and results: Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry, we captured 1319 diabetics with multivessel disease requiring revascularization for an acute coronary syndrome (January 2009-December 2012) and reported health status using the Seattle Angina Questionnaire (SAQ) at baseline, 1, 3 and 5-years [599 underwent coronary artery bypass grafting (CABG); 720 underwent percutaneous coronary intervention (PCI)]. Adjusted analyses were performed using a propensity score-matching technique. After adjustment (including baseline SAQ domain scores), 1-year mean (95% CI) SAQ scores (range 0-100 with higher scores reflecting improved health status) were significantly greater in selected domains for CABG compared to PCI (exertional capacity: 81.7 [79.5-84.0] vs. 78.8 [76.5-81.0], P = 0.07; angina stability: 83.1 [80.4-85.9] vs. 75.0 [72.3-77.8], P < 0.001]; angina frequency 93.2 [91.6-95.0] vs. 90.0 [87.8-91.3], P = 0.003; treatment satisfaction: 93.6 [92.2-94.9] vs. 90.8 [89.2-92.0], P = 0.003; quality of life [QOL]: 83.8 [81.7-85.8] vs. 77.2 [75.2-79.2] P < 0.001). At 3-years, these benefits were attenuated (exertional capacity: 79.3 [76.9-81.7] vs. 78.7 [76.3-81.1], P = 0.734; angina stability 79.3 [76.3-82.3] vs. 75.5 [72.5-78.5], P = 0.080; angina frequency: 93.2 [91.3-95.1] vs. 90.9 [89.0-92.8], P = 0.095; treatment satisfaction: 92.5 [91.0-94.0] vs. 91.5 [90.0-93.0] P = 0.382; QOL: 83.2 [81.1-85.2] vs. 80.3 [78.2-82.4], P = 0.057). At 5-years, majority of domains were similar (exertional capacity: 77.8 [75.0-80.6] vs. 76.3 [73.2-79.3], P = 0.482; angina stability: 78.0 [74.8-81.2] vs. 74.8 [71.4-78.2], P = 0.175; angina frequency: 94.2 [92.3-96.0] vs. 90.9 [89.0-92.9], P = 0.018; treatment satisfaction: 93.7 [92.2-95.1] vs. 92.2 [90.6-93.7], P = 0.167; QOL: 84.1 [82.0-86.3] vs. 81.1 [78.8-83.4], P = 0.058). Majority in both groups remained angina-free at 5-years (75.0% vs. 70.3%, P = 0.15). Conclusion: Improvements in health status with CABG compared with PCI were not sustained long-term. This temporal sequence should be considered when contemplating a revascularization strategy in diabetics with multivessel disease.

Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 T.

Lithium has been the mainstay of treatment for bipolar disorder. Early studies suggest that lithium acts via inositol depletion. This study assesses the effect of 1, 2 and 4 weeks of lithium treatment on myo-inositol concentrations across several brain regions. Thirty-six Sprague-Dawley rats were treated for 2 weeks with an intraperitoneal injection of either 1 mmol/kg/day, twice daily lithium chloride (n=18) or placebo (2 ml/kg of saline) (n=18). The rats were separated into three groups: 1 week, 2 weeks and 4 weeks. Brains were dissected into prefrontal, temporal and occipital cortical areas, as well as hippocampus, and analyzed at 18.8 T. Myo-inositol was quantified using the Chenomx Profiler software. Lithium did not alter myo-inositol concentrations at 1 week. A significant reduction exists in myo-inositol concentrations in lithium-treated rats at 2 and 4 weeks, across all four brain regions. Studies suggest brain region-specific alterations in myo-inositol concentrations among bipolar patients. Our findings suggest that lithium-induced reduction of myo-inositol is more global.

Valproate attenuates dextroamphetamine-induced subjective changes more than lithium.

Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.