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.

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.

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.

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.

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.

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.

Efficacy and safety of a routine early invasive strategy in relation to time from symptom onset to fibrinolysis (a subgroup analysis of TRANSFER-AMI).

The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis.

Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials.

OBJECTIVES: This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis. BACKGROUND: The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain. METHODS: Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models. RESULTS: Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01). CONCLUSIONS: Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182).

Multimodality imaging for resuscitated sudden cardiac death.

We present a case that elegantly illustrates the utility of two novel noninvasive imaging techniques, computed tomography (CT) coronary angiography and cardiac MRI, in the diagnosis and management of a 27-year-old man with exertion-induced cardiac arrest caused by an anomalous right coronary artery. CT coronary angiography with 3D reformatting delineated the interarterial course of an anomalous right coronary artery compressed between the aorta and pulmonary artery, whereas cardiac MRI showed a small myocardial infarction in the right coronary artery territory not detected on echocardiography. This case highlights the value of novel multimodality imaging techniques in the risk stratification and management of patients with resuscitated cardiac arrest.

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.

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.

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.

Management and outcomes of non-ST elevation acute coronary syndromes in relation to previous use of antianginal therapies (from the Canadian Global Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary Events [CANRACE]).

Randomized trials have established the efficacy of antianginal medications in the treatment of chronic stable coronary disease. Using data from the Global Registry of Acute Coronary Events (GRACE) and Canadian Registry of Acute Coronary Events (CANRACE), we examined the temporal trends in antianginal use (beta blockers, calcium antagonists, and nitrates) before non-ST-elevation acute coronary syndrome presentation from 1999 to 2008 in 10,019 patients. The relationships among previous antianginal use, clinical characteristics on presentation, and in-hospital management and outcomes were examined. Beta blockers were the most commonly used agents, and there was a significant decline in the use of nitrates over time. Compared with patients not on any antianginal therapy before presentation, those on treatment were more likely to be older, female, and have a history of hypertension, diabetes, previous angina, and myocardial infarction; they were less likely to present with positive biomarkers (all p <0.001). Patients not on antianginal therapy before presentation were more likely to undergo coronary angiography and percutaneous coronary intervention and less likely to have recurrent ischemia during hospitalization (all p <0.001). In multivariable analysis, previous antianginal use was independently associated with lower use of coronary angiography in hospital (p = 0.034) but not with in-hospital mortality. In conclusion, there has significant temporal decline in nitrate use before non-ST-elevation acute coronary syndrome. Patients receiving antianginal therapy before presentation more frequently had preexisting cardiovascular disease and previous revascularization and were less likely to present with non-ST-segment elevation MI compared with patients on no antianginal therapies. Previous antianginal use was independently associated with a lower use of coronary angiography in hospital.