Evaluation and management of drug-eluting stent in-stent restenosis.

PURPOSE OF REVIEW: In-stent restenosis (ISR) is the most common cause of stent failure. Although the rate of ISR is significantly lower with contemporary drug-eluting stents (DES), it remains a challenging clinical entity to treat. RECENT FINDINGS: In this review, we focus on a practical approach to management of DES ISR with intravascular imaging at its core, as supported by several recently published articles. This facilitates assessment of the underlying mechanism(s) essential to the successful treatment of ISR allowing for a tailored selection of treatment modalities. SUMMARY: The successful treatment of DES ISR requires identification of the causative mechanism(s). Individualized treatment may include high-pressure balloon angioplasty alone, cutting or scoring balloons, intravascular lithotripsy, atheroablative therapies and a selection of either repeat DES implantation or drug-coated balloon treatment.

Generalizability of the REDUCE-IT trial to South Asians with cardiovascular disease.

BACKGROUND: South Asians (SAs) represent ∼25% of the world's population and account for >50% of global cardiovascular (CV) deaths, yet they continue to be underrepresented in contemporary clinical trials. The REDUCE-IT study demonstrated in a high-risk and predominantly White population that icosapent ethyl (IPE) lowered major adverse cardiovascular events by 25%. We sought to determine the generalizability of these results to a high-risk population of SAs with established CV disease living in Canada. METHODS: This was a cross-sectional observational study of 200 statin-treated SAs (≥45 years) with atherosclerotic CV disease (ASCVD) (NCT05271591). SA ethnicity was self-identified as being of Anglo-Indian, Bangladeshi, Bengali, Bhutanese, Goan, Gujarati, Indian, Jatt, Kashmiri, Maharashtrian, Malayali, Nepali, Pakistani, Punjabi, Sindhi, Sinhalese, Sri Lankan, Tamil, Telugu, or other SA. ASCVD was defined as the presence of coronary, carotid, or peripheral atherosclerosis. FINDINGS: Mean age of the cohort was 67 years, where 82% were men and 57% had diabetes. The predominant ASCVD phenotype was coronary artery disease (94%). Mean (SD) baseline LDL-C and triglycerides were 1.70 (0.8) mmol/L and 1.42 (1.0) mmol/L, respectively. Three-quarters were on high-intensity statin therapy. According to the Health Canada/Canadian Cardiovascular Society Guidelines and FDA-approved indication, 33% and 25% of the participants were, respectively, eligible for IPE. CONCLUSIONS: A large proportion of high-intensity, statin-treated, high-risk patients with ASCVD and of self-reported SA ethnicity are eligible for IPE. These data have important translational implications for SAs who are at a disproportionately higher risk of CV morbidity and mortality. FUNDING: This study was funded by an unrestricted grant provided by HLS Therapeutics Inc, Canada.

TAVR in a Patient With Anomalous Origin and Course of the Left Main Coronary Artery.

In patients with anomalous coronary arteries with high-risk features, corrective cardiac surgery should be considered. We report the first case of transcatheter aortic valve replacement using a self-expanding Evolut valve, in a patient with a single coronary artery arising from the right coronary cusp and an intramural course of the left main. (Level of Difficulty: Intermediate.).

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.

Overview of Contemporary Chronic Total Occlusion Percutaneous Coronary Intervention Techniques: A Narrative Systematic Review.

BACKGROUND: Despite the abundance of coronary chronic total occlusions (CTO) percutaneous coronary intervention (PCI) studies, the literature is not easy to digest for both general PCI operators and CTO PCI specialists because of the many varied terms used for approaches and inconsistency in terminology. This inconsistency makes it challenging to understand the advantages and disadvantages of these different approaches and, most importantly, their downstream clinical outcomes. Accordingly, we conducted a systematic review of all published studies on CTO PCI to describe techniques and algorithms used in the last decade to provide an overview on the efficacy and safety of contemporary CTO PCI techniques. METHODS: We performed a comprehensive search of the PubMed, EMBASE, and the Cochrane library databases for manuscripts about PCI of CTOs. We included studies published between the years 2005 and 2019. We categorized studies into those using a single approach (antegrade, retrograde) and those with a prespecified algorithm (ie, hybrid approach). RESULTS: Fifty-five observational studies including 28,907 patients who underwent CTO were included in this review. CTO PCI generally carries low risk of major procedural complications, with angiographic success rates being higher in studies that used an algorithmic vs single technical approach. CONCLUSIONS: This systematic review highlights the wide variation in definitions and practices in CTO PCI and calls for standardization in terminology and practice.

CONTEXTE: Malgré l'abondance d'études sur l'intervention coronarienne percutanée (ICP) en cas d'occlusion totale chronique (OTC), la littérature n'est pas facile à assimiler, tant pour les opérateurs généraux qui effectuent des ICP que pour les spécialistes des ICP en cas d'OTC, en raison des nombreux termes utilisés pour les approches et de l'incohérence sur le plan de la terminologie. Cette incohérence rend difficile la compréhension des avantages et des inconvénients de ces différentes approches et, surtout, de leurs résultats cliniques en aval. Nous avons donc procédé à une revue systématique de toutes les études publiées sur l'ICP en cas d'OTC afin de décrire les techniques et les algorithmes utilisés au cours de la dernière décennie et de donner un aperçu de l'efficacité et de l'innocuité des techniques contemporaines d'ICP en cas d'OTC. MÉTHODOLOGIE: Nous avons effectué une recherche exhaustive dans les bases de données PubMed, EMBASE et Cochrane Library pour trouver des articles sur l'ICP en cas d'OTC. Nous avons retenu les études publiées entre 2005 et 2019. Nous avons classé ces études en deux catégories : celles qui utilisent une seule approche (antérograde, rétrograde) et celles qui utilisent un algorithme prédéfini (approche hybride). RÉSULTATS: Cette revue portait sur 55 études observationnelles, pour un total de 28 907 patients présentant des OTC. L'ICP en cas d'OTC comporte généralement un faible risque de complications importantes liées aux interventions, les taux de réussite angiographique étant plus élevés pour les études où une approche algorithmique était utilisée que pour celles où l'on recourait à une approche technique unique. CONCLUSIONS: Cette revue systématique souligne la grande variation des définitions et des pratiques en matière d'ICP en cas d'OTC, ainsi que le besoin d'une normalisation de la terminologie et de la pratique.

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.

Culprit plaque morphology in STEMI - an optical coherence tomography study: insights from the TOTAL-OCT substudy.

AIMS: Our aim was to compare stenosis severity and plaque content between STEMI culprit lesions with intact fibrous cap (IFC) and those with plaque rupture (PR) in a prospective study. METHODS AND RESULTS: We evaluated 93 patients undergoing OCT and thrombectomy as part of a prospective substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial. Culprit lesion morphology was assessable by OCT in 70/93 (75.3%). IFC was found in 31 (44.3%), PR in 34 (48.6%) and calcified nodule in five (7.1%) patients. Following thrombectomy, OCT demonstrated similar lumen area stenosis in IFC (79.3%) and PR (79.6%) (p=0.88). Lumen area stenosis <50% was observed in none of the patients with PR and in one patient with IFC. IFC had fewer quadrants with lipid plaque as compared to PR (28.16±15.02 vs. 39.12±14.23, p=0.004). However, in both lesion types, lipid was the predominant plaque type (83.9 vs. 63.7% of diseased quadrants). CONCLUSIONS: In a prospective study of STEMI patients treated with thrombectomy, mild residual stenoses were uncommon in IFC lesions. Although lipid content was lower than in PR lesions, lipid composed the majority of the diseased segments in IFC.

Pharmacodynamic and clinical implications of switching between P2Y12 receptor antagonists: considerations for practice.

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

eNOS overexpressing bone marrow cells are safe and effective in a porcine model of myocardial regeneration following acute myocardial infarction.

AIM: Cell therapy has been shown to be effective in improving LV function postmyocardial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI. METHODS: Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. Bone marrow cells were cultured for 7 days, and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n = 5), nontransfected BMCs (nt-BMC, n = 4), or phosphate-buffered saline (PBS) control (n = 6). Cardiac MRI was performed at baseline (1 week post-MI) and 6 weeks post-MI. RESULTS: There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at 6 weeks showed a trend toward improvement in both cell therapy groups compared with baseline but worsened in the PBS control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6 weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group. CONCLUSIONS: Bone marrow cell delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7 days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement in left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function.

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI.

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

Free-breathing, nongated real-time delayed enhancement MRI of myocardial infarcts: a comparison with conventional delayed enhancement.

PURPOSE: To compare a free-breathing, nongated, and black-blood real-time delayed enhancement (RT-DE) sequence to the conventional inversion recovery gradient echo (IR-GRE) sequence for delayed enhancement MRI. MATERIALS AND METHODS: Twenty-three patients with suspected myocardial infarct (MI) were examined using both the IR-GRE and RT-DE imaging sequences. The sensitivity and specificity of RT-DE for detecting MI, using IR-GRE as the gold standard, was determined. The contrast-to-noise ratios (CNR) between the two techniques were also compared. RESULTS: RT-DE had a high sensitivity and specificity (94% and 98%, respectively) for identifying MI. The total acquisition time to image the entire left ventricle was significantly shorter using RT-DE than IR-GRE (5.6+/-0.9 versus 11.5+/-1.9 min). RT-DE had a slightly lower infarct-myocardium CNR but a higher infarct-blood CNR than IR-GRE imaging. Compared with IR-GRE, RT-DE accurately measured total infarct sizes. CONCLUSION: RT-DE can be used for delayed enhancement imaging during free-breathing and without cardiac gating.

Local hospital vs. core-laboratory interpretation of the admission electrocardiogram in acute coronary syndromes: increased mortality in patients with unrecognized ST-elevation myocardial infarction.

AIMS: Previous analyses suggest only modest agreement between local site and core-laboratory (core-lab) electrocardiogram (ECG) interpretation in patients with acute coronary syndromes (ACSs); however, this has not been well examined outside of clinical trial populations. METHODS AND RESULTS: Patients (n = 5277 from 51 hospitals; 4916 with 1 year vital status) participating in the Canadian ACS Registry who were hospitalized with an ACS and had an interpretable initial ECG were included in this study. Core-lab ECG interpretation was blinded to site interpretation and outcomes. There was moderate agreement between site and core-lab regarding the predominant ECG findings (kappa = 0.49). Patients with core-lab-defined ST-elevation and cardiac marker elevation (n = 1202) not classified as ST-elevation by the site were less likely to receive acetylsalicylic acid (ASA) (90 vs. 96%, P < 0.0001), heparin (91 vs. 95%, P = 0.04), and reperfusion therapy (14 vs. 76%, P < 0.0001) than patients for whom there was agreement that ST-elevation was present. After adjusting for other validated prognostic factors, site-unrecognized ST-elevation was independently associated with higher mortality (odds ratio = 2.21; 95% CI, 1.46-3.36; P < 0.001). CONCLUSIONS: In patients with ACS, there was only moderate agreement between core-lab and site interpretation of the initial ECG. Site-unrecognized ST-elevation myocardial infarction was associated with underutilization of evidence-based therapies and increased 1-year mortality.

Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials.

OBJECTIVES: We sought to best estimate the benefits and risks associated with rescue percutaneous coronary intervention (PCI) and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST-segment myocardial infarction (STEMI). BACKGROUND: Fibrinolytic therapy is the most common treatment for STEMI; however, the best therapy in patients who fail to achieve reperfusion after fibrinolytic therapy remains uncertain. METHODS: We performed a meta-analysis of randomized trials using a fixed-effects model. We included 8 trials enrolling 1,177 patients with follow-up duration ranging from hospital discharge to 6 months. RESULTS: Rescue PCI was associated with no significant reduction in all-cause mortality (relative risk [RR] 0.69; 95% confidence interval [CI] 0.46 to 1.05), but was associated with significant risk reductions in heart failure (RR 0.73; 95% CI 0.54 to 1.00) and reinfarction (RR 0.58; 95% CI 0.35 to 0.97) when compared with conservative treatment. Rescue PCI was associated with an increased risk of stroke (RR 4.98; 95% CI 1.10 to 22.5) and minor bleeding (RR 4.58; 95% CI 2.46 to 8.55). Repeat fibrinolytic therapy was not associated with significant improvements in all-cause mortality (RR 0.68; 95% CI 0.41 to 1.14) or reinfarction (RR 1.79; 95% CI 0.92 to 3.48), but was associated with an increased risk for minor bleeding (RR 1.84; 95% CI 1.06 to 3.18). CONCLUSIONS: Rescue PCI is associated with improved clinical outcomes for STEMI patients after failed fibrinolytic therapy, but these benefits must be interpreted in the context of potential risks. On the other hand, repeat fibrinolytic therapy is not associated with significant clinical improvement and may be associated with increased harm.