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.

Collagenase to facilitate guidewire crossing in chronic total occlusion PCI-The Total Occlusion Study in Coronary Arteries-5 (TOSCA-5) trial.

BACKGROUND: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO. AIMS: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty. METHODS: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites: 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 µg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 µg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only. RESULTS: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 µg, and 29% in 1200 µg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups. CONCLUSION: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent.

Repatriation to referral hospital after reperfusion of STEMI patients transferred for primary percutaneous coronary intervention: Insights of a Canadian regional STEMI care system.

BACKGROUND: In regional systems of ST-segment elevation myocardial infarction (STEMI) care, patients presenting to hospitals without percutaneous coronary intervention (PCI) are transferred to PCI-capable hospitals for primary PCI. Repatriation, a practice whereby such patients are transferred back to non-PCI referral hospitals after reperfusion is prevalent in many jurisdictions, yet little is known of this practice and its safety. METHODS: We studied 979 consecutive STEMI patients transported from the emergency department and catchment area of two non-PCI hospitals in Ontario, Canada to a regional PCI-hospital for primary PCI between January 2008 and June 2014. Logistic regression modeling was performed to determine factors associated with delayed repatriation beyond 24 hours and to evaluate the association between repatriation and index-admission mortality. RESULTS: Eight hundred and fifteen (83.2%) patients were repatriated with 524 (65.2%) patients repatriated within 24 hours. Factors independently associated with delayed repatriation included systolic blood pressure (OR 1.03 per 5 mmHg decrease, 95% CI 1.01-1.06, P= .04), requirement for mechanical ventilation (OR 24.9, 95% CI 5.4-115.3, P< .0001), ventricular arrhythmia (OR 3.0, 95% CI 1.3-6.6, P= .01), infarct-related artery (P= .03), final TIMI flow grade (P= .01) and access-site complications (OR 2.36, 95% CI 1.04-5.4, P= .04). After repatriation, 9 (1.3%) patients returned to the PCI-hospital for urgent care, and 16 (2.0%) died during index-admission. After adjustment, repatriation was not associated with increase in index-admission mortality (adjusted OR 0.46, 95% CI 0.16-1.32, P= .15). CONCLUSIONS: In a regional STEMI care system in Ontario, Canada, patients are routinely repatriated to non-PCI hospitals after primary PCI. This practice was associated with very low and acceptable rate of return to the PCI-hospital during index-admission without an adverse impact on short-term outcomes.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis.

PURPOSE: To investigate the potentially improved detection and quantification of cardiac involvement using novel late-gadolinium-enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis. MATERIALS AND METHODS: Twenty-eight patients with systemic sarcoidosis underwent a cardiac magnetic resonance imaging (CMR) study on a 1.5T system. Precontrast CMR included left ventricular (LV) and right ventricular (RV) function and quantitative T2 measurement. Postcontrast LGE-MRI included inversion-recovery fast-gradient-echo (IR-FGRE) and multicontrast late-enhancement imaging (MCLE). RESULTS: LV functional parameters were normal in all patients (LVEF=61.2±8.5%) including with cardiac involvement (LVEF=59.4±12.1%) and without (LVEF=61.7±7.5%) while the average RV function was comparatively decreased (RVEF=48.0±6.6%, P<0.0001). 21.4% of patients had cardiac involvement showing patchy or multiple focal hyperenhancement patterns in LV free wall, papillary muscles (PM), or interventricular septum. In two cases with PM involvement, the PM abnormal LGE foci were only observed on MCLE. For precontrast T2 measurements, a significantly decreased T2 measurement was observed in regions demonstrating LGE, compared to the LGE-negative group (focal LGE-positive regions vs. negative: 40.0±2.4 msec vs. 53.0±2.6 msec, P<0.0001). CONCLUSION: LGE-MRI can identify cardiac involvement in systemic sarcoidosis. MCLE might be more sensitive at detecting subtle myocardial lesion. The decreased T2 observed in cardiac sarcoid may reflect its inactive phase, thus might provide a noninvasive method for monitoring disease activity or therapy.

Angio-Seal Closure for Traumatic Left Subclavian Artery Pseudoaneurysm: A Case Report.

Subclavian artery pseudoaneurysms are rare and associated with high morbidity and mortality. Alternative approaches to open surgical repair can include endovascular repair or ultrasound-guided thrombin injection. Here, we describe a safe and novel technique of closure of a subclavian artery pseudoaneurysm with Angio-Seal that was unresponsive to thrombin injection and in a difficult location for open repair.

Reproducibility study for free-breathing measurements of pyruvate metabolism using hyperpolarized (13) C in the heart.

Spatially resolved images of hyperpolarized (13) C substrates and their downstream products provide insight into real-time metabolic processes occurring in vivo. Recently, hyperpolarized (13) C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time-resolved cardiac- and respiratory-gated images of [1-(13) C] pyruvate, [1-(13) C] lactate, and (13) C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free-breathing measurements is demonstrated using the time-resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60-min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients.

Multi-contrast late enhancement CMR determined gray zone and papillary muscle involvement predict appropriate ICD therapy in patients with ischemic heart disease.

BACKGROUND: Myocardial infarct heterogeneity indices including peri-infarct gray zone are predictors for spontaneous ventricular arrhythmias events after ICD implantation in patients with ischemic heart disease. In this study we hypothesize that the extent of peri-infarct gray zone and papillary muscle infarct scores determined by a new multi-contrast late enhancement (MCLE) method may predict appropriate ICD therapy in patients with ischemic heart disease. METHODS: The cardiovascular magnetic resonance (CMR) protocol included LV functional parameter assessment and late gadolinium enhancement (LGE) CMR using the conventional method and MCLE post-contrast. The proportion of peri-infarct gray zone, core infarct, total infarct relative to LV myocardium mass, papillary muscle infarct scores, and LV functional parameters were statistically compared between groups with and without appropriate ICD therapy during follow-up. RESULTS: Twenty-five patients with prior myocardial infarct for planned ICD implantation (age 64±10 yrs, 88% men, average LVEF 26.2±10.4%) were enrolled. All patients completed the CMR protocol and 6-46 months follow-up at the ICD clinic. Twelve patients had at least one appropriate ICD therapy for ventricular arrhythmias at follow-up. Only the proportion of gray zone measured with MCLE and papillary muscle infarct scores demonstrated a statistically significant difference (P < 0.05) between patients with and without appropriate ICD therapy for ventricular arrhythmias; other CMR derived parameters such as LVEF, core infarct and total infarct did not show a statistically significant difference between these two groups. CONCLUSIONS: Peri-infarct gray zone measurement using MCLE, compared to using conventional LGE-CMR, might be more sensitive in predicting appropriate ICD therapy for ventricular arrhythmia events. Papillary muscle infarct scores might have a specific role for predicting appropriate ICD therapy although the exact mechanism needs further investigation.

Papillary muscle involvement in myocardial infarction: initial results using multicontrast late-enhancement MRI.

We hypothesized that multicontrast late-enhancement (MCLE) MRI would improve the identification of papillary muscle involvement (PM-MI) in patients with myocardial infarction (MI), compared with conventional late gadolinium enhancement (LGE) MRI using the inversion recovery fast gradient echo (IR-FGRE) technique. Cardiac LGE-MRI studies using both MCLE and IR-FGRE pulse sequences were performed on a 1.5 Tesla (T) MRI system in 23 patients following MI. In all patients, PM-MI was confirmed by the diagnostic criteria as outlined below: (a) the increased signal intensity of PM was the same or similar to that of adjacent hyper-enhanced left ventricular (LV) infarct segments; and (b) the hyper-enhanced PM region was limited to the PM area defined by precontrast cine images of steady-state free precession (SSFP). Visual contrast score was rated according to the differentiation between LV blood pool and hyper-enhanced infarct myocardium. Quantitative contrast-noise ratios (CNR) of infarct relative to blood pool and viable myocardium were also measured on MCLE and IR-FGRE images. Of these 23 patients, 13 studies demonstrated primarily involvement of the territories of the right coronary (RCA, 8 patients) and/or left circumflex (LCX, 5 patients) arteries and 10 involved the territories of left anterior descending artery (LAD) with some LCX involvement. Although both IR-FGRE and MCLE determined the presence and extent of LV MI, better visual contrast scores were achieved in MCLE (2.9 ± 0.3) compared with IR-FGRE (1.6 ± 0.8, P < 0.001). The CNRs of infarct relative to LV blood pool showed a significant statistical difference (n = 23, P < 0.00001) between MCLE (16.2 ± 7.2) and IR-FGRE images (4.8 ± 4.1), which is consistent with the result of visual contrast scores between infarct and LV blood pool. The CNRs of infarct versus viable myocardium did not demonstrate a significant statistical difference (n = 23, P = 0.61) between MCLE (14.4 ± 7.0) and IR-FGRE images (13.6 ± 6.1). MCLE clearly demonstrated PM-MI in all cases (100%, 23/23) while only 39% (9/23) could be visualized on the corresponding IR-FGRE images. In conclusion, MCLE imaging provides better contrast between blood pool and infarct myocardium, thus improving the determination of PM-MI.

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.

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.