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.

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.

Safety and Performance of the Orsiro Sirolimus-Eluting Stent in the Treatment of All-Comers Patient Population in Daily Clinical Practice.

BACKGROUND: The BIOFLOW-III Canada registry aimed to evaluate the safety and efficacy of Orsiro sirolimus-eluting stents (SES) with biodegradable polymer, in an all-comers patient population. METHODS: We conducted a prospective, non-randomized, multi-center, observational all-comers registry of patients undergoing percutaneous coronary intervention (PCI) with Orsiro SES at two high-volume Canadian centers. The primary endpoint was one-year target lesion failure (TLF) defined as a composite of cardiac death, target-vessel myocardial infarction (MI), coronary artery bypass grafting and clinically driven target lesion revascularization. Four subgroups were pre-defined: i) diabetic patients; ii) small vessels (≤2.75 mm); iii) chronic total occlusions (CTO) and iv) acute MI. RESULTS: From May 2014 to July 2016, 250 patients (mean age 66.2 ± 10.8 years, 75.6% males, 30% diabetes) underwent PCI with Orsiro SES for 385 coronary lesions. The mean stent diameter was 2.98 ± 0.50 mm and the mean stent length was 22 ± 8 mm. Clinical device and procedural success rates were with 99.5% and 97.6%, respectively. The overall one-year TLF rate was 2.8% [95% confidence interval (CI) 1.4-5.8%], whereas TLF rates were 4.1% [95%CI 1.3-12.2%], 3.2% [95%CI 1.2-8.4%], 8.3% [95%CI 2.2-29.4%], and 2.6% [95%CI 0.7-9.9%] in patients with diabetes, small vessels, CTO, and acute MI, respectively. One case of possible stent thrombosis (ST) was reported (0.4% [95%CI 0.1-2.8%]), while no cases of definite/probable ST was observed at one year. CONCLUSION: Our data provide further evidence of the safety and clinical performance of Orsiro SES in an unselected, real-world, complex patient population. CONDENSED ABSTRACT: The BIOFLOW-III Canada registry is a prospective, non-randomized, multi-center, observational all-comers registry designed to evaluate the safety and performance of the Orsiro SES in non-selected, real-world patients. A total of 250 patients (mean age 66.2 ± 10.8 years, 75.6% males, 30% diabetes) who underwent PCI with Orsiro SES, were enrolled at two high-volume Canadian centers. The overall rate of TLF at one year was 2.8% [95%CI 1.4-5.8%], whereas TLF rates were 4.1%, 3.2%, 8.3%, and 2.6% in patients with diabetes, small vessels ≤2.75 mm, CTO, and acute MI, respectively. No case of definite/probable ST was observed.

Early diastolic strain rate measurements by cardiac MRI in breast cancer patients treated with trastuzumab: a longitudinal study.

We evaluated temporal changes in early diastolic strain rates by cardiovascular magnetic resonance (CMR) as an early detector of trastuzumab-induced ventricular dysfunction. We conducted a prospective, multi-centre, longitudinal observational study of 41 trastuzumab-treated breast cancer women who underwent serial CMR (baseline, 6, 12, and 18 months). Two blinded readers independently measured left ventricular ejection fraction (LVEF), peak systolic strain parameters (global longitudinal strain [GLS] and global circumferential strain [GCS]), and early diastolic strain rate parameters (global longitudinal diastolic strain rate [GLSR-E], global circumferential diastolic strain rate [GCSR-E], and global radial diastolic strain rate [GRSR-E]), by feature tracking (FT-CMR) using CMR42. There was a significant decline in peak systolic strain GLS and GCS at 6 months (p = 0.024 and p < 0.001, respectively) and 12 months (p = 0.002 and p < 0.001, respectively), followed by recovery at 18 months, which paralleled decline in LVEF at 6 months (p = 0.034) and 12 months (p = 0.012). Conversely, early diastolic strain rates GLSR-E and GCSR-E did not significantly change over 18 months (p > 0.10), while GRSR-E was marginally significant at 12 months (p = 0.021). There was no significant correlation between changes at 6 months in LVEF and GLSR-E or GRSR-E (p > 0.10), and a marginally significant weak correlation between LVEF and GCSR-E (p = 0.046). Among trastuzumab-treated patients without overt cardiotoxicity, there was no consistent temporal change in FT-CMR-derived diastolic strain rate parameters up to 18 months, in contrast to decline in systolic strain and LVEF. Systolic strains by FT-CMR are likely more useful than diastolic strain rates for monitoring subclinical trastuzumab-related myocardial dysfunction.ClinicalTrials.gov identifier NCT01022086.

Cardiac MRI and radionuclide ventriculography for measurement of left ventricular ejection fraction in ICD candidates.

OBJECTIVE: Current guidelines provide left ventricular ejection fraction (LVEF) criterion for use of implantable cardioverter defibrillators (ICD) but do not specify which modality to use for measurement. We compared LVEF measurements by radionuclide ventriculography (RNV) vs cardiac MRI (CMR) in ICD candidates to assess impact on clinical decision making. METHODS: This single-centre study included 124 consecutive patients referred for assessment of ICD implantation who underwent RNV and CMR within 30 days for LVEF measurement. RNV and CMR were interpreted independently by experienced readers. RESULTS: Among 124 patients (age 64 ±â€¯11 years, 77% male), median interval between CMR and RNV was 1 day; mean LVEF was 32 ±â€¯12% by CMR and 33 ±â€¯11% by RNV (p = 0.60). LVEF by CMR and RNV showed good correlation, but Bland-Altman analysis showed relatively wide limits of agreement (-12.1 to 11.4). CMR LVEF reclassified 26 (21%) patients compared to RNV LVEF (kappa = 0.58). LVEF by both modalities showed good interobserver reproducibility (ICC 0.96 and 0.94, respectively) (limits of agreement -7.27 to 5.75 and -8.63 to 6.34, respectively). CONCLUSION: Although LVEF measurements by CMR and RNV show moderate agreement, there is frequent reclassification of patients for ICD placement based on LVEF between these modalities. Future studies should determine if a particular imaging modality for LVEF measurement may enhance ICD decision making and treatment benefit.

Management of Chronic Total Coronary Occlusion in Stable Ischemic Heart Disease by Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Versus Medical Therapy.

Coronary chronic total occlusions (CTOs) are found in approximately 20% of angiograms. We sought to assess the variation in the management of patients with CTOs and to compare the clinical outcomes of CTO lesions with those of non-CTO lesions. We conducted a population-based cohort study and included all patients with stable angina who underwent cardiac catheterization from October 1, 2012, to June 30, 2013, in Ontario, Canada. The primary outcome was a composite of mortality and hospitalization for myocardial infarction. A total of 7,864 patients were included, of whom 2,279 (29%) had a CTO. There were substantial differences in revascularization rates for patients with CTOs across hospitals in Ontario (44.9% to 94.1%). Revascularization was associated with improved outcomes in the overall cohort. Although the advantage of coronary artery bypass grafting over medical therapy was consistent in both patients with CTOs and patients without CTOs, the benefit of percutaneous coronary intervention (PCI) was limited to patients without CTOs (hazard ratio 0.56, 95% confidence interval 0.40- to 0.78), with no difference in patients with CTOs. The CTO lesion, however, was revascularized in few of the PCI cases (41.1%), with PCI limited to the non-CTO lesion in most patients.

Predictors of Successful Hybrid-Approach Chronic Total Coronary Artery Occlusion Stenting: An Improved Model With Novel Correlates.

OBJECTIVES: The aim of this study was to develop a hybrid approach-specific model to predict chronic total coronary artery occlusion (CTO) percutaneous coronary intervention success, useful for experienced but not ultra-high-volume operators. BACKGROUND: CTO percutaneous coronary intervention success rates vary widely and have improved with the "hybrid approach," but current predictive models for success have major limitations. METHODS: Data were obtained from consecutively attempted patients from 7 clinical sites (9 operators, mean annual CTO volume 61 ± 17 cases). Angiographic analysis of 21 lesion variables was performed centrally. Statistical modeling was performed on a randomly designated training group and tested in a separate validation cohort. The primary outcome of interest was technical success. RESULTS: A total of 436 patients (456 lesions) met entry criteria. Twenty-five percent of lesions had prior failed percutaneous coronary interventions at the site. The right coronary artery was the most common location (56.4%), and mean occlusion length was 24 ± 20 mm. The initial approach was most often antegrade wire escalation (70%), followed by retrograde (22%). Success was achieved in 79.4%. Failure was most closely correlated with presence of an ambiguous proximal cap, and in the presence of an ambiguous proximal cap, specifically defined collateral score (combination of Werner and tortuosity scores) and retrograde tortuosity. Without an ambiguous proximal cap, poor distal target, occlusion length >10 mm, ostial location, and 1 operator variable contributed. Prior failure, and Werner and tortuosity scores alone, were only weakly correlated with outcomes. The basic 7-item model predicted success, with C statistics of 0.753 in the training cohort and 0.738 in the validation cohort, the later superior (p < 0.05) to that of the J-CTO (Multicenter CTO Registry of Japan) (0.55) and PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) (0.61) scores. CONCLUSIONS: Success can be reasonably well predicted, but that prediction requires modification and combination of angiographic variables. Differences in operator skill sets may make it challenging to create a powerful, generalizable, predictive tool.

Relationships Between Left Ventricular Structure and Function According to Cardiac MRI and Cardiac Biomarkers in End-Stage Renal Disease.

BACKGROUND: We sought to assess the relationships between left ventricular (LV) remodelling and the mechanical and uremic stressors in hemodialysis patients. METHODS: In this prospective 2-centre cohort study, 67 prevalent hemodialysis patients were followed for 1 year. Data on routine bloodwork and predialysis blood pressure (BP) measurements were collected over a 12-week period. LV end-diastolic volume (LVEDV) and LV mass (LVM) were measured using cardiac magnetic resonance imaging and indexed. High-sensitivity troponin-I (hsTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), fibroblast growth factor 23 (FGF-23), and high-sensitivity C-reactive protein (hsCRP) were also measured. All study procedures were performed at baseline and at 1 year. We examined the relationships between LV remodelling and (1) NT-proBNP and hsTnI (LV stretch and injury); (2) ultrafiltration volume (UFV) and interdialytic weight gain (IDWT; volume overload); (3) predialysis BP measurements (pressure overload); and (4) biomarkers of inflammation (hsCRP) and fibrosis (FGF-23). RESULTS: LVEDV was significantly associated with UFV and with IDWT, at baseline as well as at 1 year. NT-proBNP was significantly and negatively correlated with UFV and IDWT, respectively, at 1 year. There were significant correlations between systolic BP and LVM index, at baseline and at 1 year as well as longitudinally. Systolic BP was the only parameter longitudinally correlated with LVM/LVEDV. hsTnI was not associated with urea, parathyroid hormone, calcium, phosphorus, FGF-23, hsCRP, or hemoglobin. CONCLUSIONS: We did not observe significant relationships between myocardial injury and markers of fibrosis, inflammation, and LV remodelling. Elevated predialysis systolic BP, which might represent a common mediator of pressure and volume overload, appears to be a dominant stimulus for LV remodelling.

Analysis of primary fine particle national ambient air quality standard metrics.

In accordance with the Clean Air Act, the U.S. Environmental Protection Agency (EPA) is currently reviewing its National Ambient Air Quality Standards for particulate matter, which are required to provide an adequate margin of safety to populations, including susceptible subgroups. Based on the latest scientific, health, and technical information about particle pollution, EPA staff recommends establishing more protective health-based fine particle standards. Since the last standards review, epidemiologic studies have continued to find associations between short-term and long-term exposure to particulate matter and cardiopulmonary morbidity and mortality at current pollution levels. This study analyzed the spatial and temporal variability of fine particulate (PM2.5) monitoring data for the Northeast and the continental United States to assess the protectiveness of various levels, forms, and combinations of 24-hr and annual health-based standards currently recommended by EPA staff and the Clean Air Scientific Advisory Committee. Recommended standards have the potential for modest or substantial increases in protection in the Northeast, ranging from an additional 13-83% of the population of the region who are living in areas not likely to meet new standards and thereby benefiting from compliance with more protective air pollution controls. Within recommended standard ranges, an optimal 24-hr (98th percentile)/annual standard suite occurs at 30/12 microg/m3, providing short- and long-term health protection for a substantial percentage of both Northeast (84%) and U.S. (78%) populations. In addition, the Northeast region will not benefit as widely as the nation as a whole if less stringent standards are selected. Should the 24-hr (98th percentile) standard be set at 35 microg/m3, Northeast and U.S. populations will receive 16-48% and 7-17% less protection than a 30 microg/m3 standard, respectively, depending on the level of the annual standard. A 30/12 microg/m3 standard suite also provides nearly equivalent 24-hr and annual control of PM2.5 distributions across the United States, thereby ensuring a more uniform and consistent level of protection than unmatched or "controlling" and "backstop" standards. This could occur even within EPA staff's recommended range of standard suites, where 22-43% of the monitors in the country could meet a controlling standard but fail to meet the combined backstop standard, resulting in inconsistent short- and long-term protection across the country. An equivalent standards combination of 30/12 microg/m3 would minimize the wide variation of protectiveness of 24-hr and annual PM2.5 concentrations. Furthermore, given recent associations of subdaily exposures and acute adverse health effects, in the absence of a subdaily averaging metric, a stringent 24-hr standard will more effectively control maximum hourly and multihourly peak concentrations than a weaker standard.

Sealing Intermediate Nonobstructive Coronary Saphenous Vein Graft Lesions With Drug-Eluting Stents as a New Approach to Reducing Cardiac Events: A Randomized Controlled Trial.

BACKGROUND: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE). METHODS AND RESULTS: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26). CONCLUSIONS: Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443.

Radial versus femoral access for percutaneous coronary intervention in ST-elevation myocardial infarction patients treated with fibrinolysis: Results from the randomized routine early invasive clinical trials.

BACKGROUND: To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis. METHODS: Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction. RESULTS: 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk. CONCLUSIONS: In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality. SUMMARY: This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality.

Fine particulate matter national ambient air quality standards: public health impact on populations in the northeastern United States.

In this article we identify the magnitude of general and susceptible populations within the northeastern United States that would benefit from compliance with alternative U.S. Environmental Protection Agency (EPA) annual and 24-hr mass-based standards for particulate matter (PM) with an aerodynamic diameter < or = 2.5 microm (PM2.5). Understanding the scale of susceptibility in relation to the stringency or protectiveness of PM standards is important to achieving the public health protection required by the Clean Air Act of 1970. Evaluative tools are therefore necessary to place into regulatory context available health and monitoring data appropriate to the current review of the PM National Ambient Air Quality Standards (NAAQS). Within the New England, New Jersey, and New York study area, 38% of the total population are < 18 or > or =65 years of age, 4-18% of adults have cardiopulmonary or diabetes health conditions, 12-15% of children have respiratory allergies or lifetime asthma, and 72% of all persons (across child, adult, and elderly age groups) live in densely populated urban areas with elevated PM2.5 concentrations likely creating heightened exposure scenarios. The analysis combined a number of data sets to show that compliance with a range of alternative annual and 24-hr PM2.5 standard groupings would affect a large fraction of the total population in the Northeast. This work finds that current PM2.5 standards in the eight-state study area affect only 16% of the general population, who live in counties that do not meet the existing annual/24-hr standard of 15/65 microg/m3. More protective PM2.5 standards recommended or enacted by California and Canada would protect 84-100% of the Northeast population. Standards falling within current ranges recommended by the U.S. EPA would protect 29-100% of the Northeast population. These considerations suggest that the size of general and susceptible populations affected by the stringency of alternative PM standards has broad implications for risk management and direct bearing on the U.S. EPA's current NAAQS review and implementation.