Multivariate Base Rates of Low Neuropsychological Test Scores in Cognitively Intact Older Adults with Subjective Cognitive Decline from a Specialist Memory Clinic.

OBJECTIVE: To avoid misdiagnosing mild cognitive impairment (MCI), knowledge of the multivariate base rates (MVBRs) of low scores on neuropsychological tests is crucial. Base rates have typically been determined from normative population samples, which may differ from clinically referred samples. The current study addresses this limitation by calculating the MVBR of low or high cognitive scores in older adults who presented to a memory clinic experiencing subjective cognitive decline but were not diagnosed with MCI. METHOD: We determined the MVBRs on the Kaplan-Baycrest Neurocognitive Assessment for 107 cognitively healthy older adults (M age = 75.81), by calculating the frequency of patients producing n scores below or above different cut-off values (i.e., 1, 1.5, 2.0, 2.5 SD from the mean), stratifying by education and gender. RESULTS: Performing below or above cut-off was common, with more stringent cut-offs leading to lower base rates (≥1 low scores occurred in 84.1% of older adults at -1 SD, 55.1% at -1.5 SD, and 39.3% at -2 SD below the mean; ≥1 high scores occurred in 80.4% of older adults at +1 SD, 35.5% at +1.5 SD, and 16.8% at +2 SD above the mean). Higher education was associated with varying base rates. Overall, the MVBR of obtaining a low cognitive test score was higher in this clinic sample, compared with prior studies of normative samples. CONCLUSIONS: MVBRs for clinically referred older adults experiencing memory complaints provide a diagnostic benefit, helping to prevent attributing normal variability to cognitive impairment and limiting false positive diagnoses.

The Influence of Cerebrovascular Pathology on Cluster Analysis of Neuropsychological Scores in Patients With Mild Cognitive Impairment.

OBJECTIVES: The diagnostic entity of mild cognitive impairment (MCI) is heterogeneous, highlighting the need for data-driven classification approaches to identify patient subgroups. However, these approaches can be strongly determined by sample characteristics and selected measures. Here, we applied a cluster analysis to an MCI patient database from a neuropsychology clinic to determine whether the inclusion of patients with MCI with vascular pathology would result in a different classification of subgroups. METHODS: Participants diagnosed with MCI (n = 166), vascular cognitive impairment-no dementia (n = 26), and a group of older adults with subjective cognitive concerns but no objective impairment (n = 144) were assessed using a full neuropsychological battery and other clinical measures. Cognitive measures were analyzed using a hierarchical cluster analysis and then a k-means approach, with resulting clusters compared on a range of demographic and clinical variables. RESULTS: We found a 4-factor solution: a cognitively intact cluster, a globally impaired cluster, an amnestic/visuospatial impairment cluster, and a mild, mixed-domain cluster. Interestingly, group differences in self-reported multilingualism emerged in the derived clusters that were not observed when comparing diagnostic groups. CONCLUSIONS: Our results were generally consistent with previous studies using cluster analysis in MCI. Including patients with primarily cerebrovascular disease resulted in subtle differences in the derived clusters and revealed new insights into shared cognitive profiles of patients beyond diagnostic categories. These profiles should be further explored to develop individualized assessment and treatment approaches.

A Randomized Controlled Trial of an Exercise Maintenance Intervention in Men and Women After Cardiac Rehabilitation (ECO-PCR Trial).

BACKGROUND: Exercise maintenance interventions are needed for cardiac rehabilitation (CR) graduates to maintain moderate and vigorous-intensity physical activity (MVPA). We tested an exercise facilitator intervention (EFI) to promote exercise maintenance compared with usual care (UC) separately in men and women. METHODS: This was a 3-site, randomized (1:1), parallel-group, superiority trial (ECO-PCR). CR graduates were stratified by site and sex and randomly allocated (concealed). EFI participants received a face-to-face introductory session, 5 small-group counseling teleconferences, and 3 personal calls from a trained facilitator over 50 weeks. In-person assessments were undertaken at baseline and 26 and 52 weeks after randomization. The primary outcome was weekly minutes of MVPA, measured by accelerometer. Secondary outcomes were exercise capacity, risk factors, quality of life, and enrollment in community-based exercise programs. Effects were tested with the use of linear mixed models. RESULTS: A total of 449 CR graduates (135 women, 314 men) were randomised (n = 226 EFI, n = 223 UC). In the intention-to-treat analysis for men and for women, there were no significant effects for treatment or time on MVPA. In a planned secondary analysis that considered only those adherent to EFI (completed ≥ 66% of sessions; per-protocol), bouted MVPA (ie, in sustained bouts of ≥ 10 min) was higher in women in the EFI group (mean = 132.6 ± 135.2 min/wk at 52 weeks) compared with UC (111.8 ± 113.1; P = 0.013). Regarding secondary outcomes, in women, a treatment group main effect was observed for blood pressure (P = 0.011) and exercise capacity (P = 0.019; both per-protocol) favouring EFI; no other differences were observed. CONCLUSIONS: In this trial of CR completers, an EFI showed promise for women, but was ineffective in men.

Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity.

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity (phenoconversion) correlated well with changes in platelet reactivity. Co-administration of omeprazole or esomeprazole in patients treated with clopidogrel results in lower CYP2C19 enzyme activity and increased platelet reactivity as measured by VASP phosphorylation test while patients given pantoprazole or ranitidine did not show any significant changes in CYP2C19 enzyme activity and platelet reactivity.

Five-year follow-up of the plaque sealing with paclitaxel-eluting stents vs medical therapy for the treatment of intermediate nonobstructive saphenous vein graft lesions (VELETI) trial.

BACKGROUND: Very few data exist on the long-term follow-up of patients with intermediate nonobstructive saphenous vein graft (SVG) lesions. The purpose of this study was to evaluate the 5-year clinical outcomes of the patients enrolled in the Moderate Vein Graft Lesion Stenting With the Taxus Stent and Intravascular Ultrasound (VELETI) and the factors associated with SVG disease progression and outcomes. METHODS: Patients with ≥ 1 intermediate SVG lesion (30%-60% diameter stenosis) were randomized to either stenting the SVG lesion with a paclitaxel-eluting stent (PES group, n = 30) or to medical treatment alone (MT group, n = 27). All patients were followed yearly up to 5 years. RESULTS: Major adverse cardiac events (MACEs) (cardiac death, myocardial infarction [MI], revascularization) related to the target SVG lesion tended to be lower in the PES group (17% vs 33%; P = 0.146) due to a lower lesion revascularization rate (13% vs 33%; P = 0.072), with no difference in cardiac death or MI between groups. MACEs related to the target SVG and global MACEs were similar between groups (P > 0.20 for both). A higher cholesterol level at baseline was the only independent predictive factor of MACEs related to the target SVG (P = 0.016). CONCLUSIONS: Over a 5-year period, one third of intermediate lesions in old SVGs progressed, leading to a cardiac event. Stenting these lesions with PESs tended to improve clinical outcomes by reducing lesion progression but not SVG failure. Higher cholesterol levels were associated with SVG disease progression and clinical events. This pilot study provides the basis for a larger trial to determine the efficacy of intermediate SVG lesion plaque sealing.

Risk score, causes, and clinical impact of failure of transradial approach for percutaneous coronary interventions.

OBJECTIVES: To study the causes of and to develop a risk score for failure of transradial approach (TRA) for percutaneous coronary intervention (PCI). BACKGROUND: TRA-PCI failure has been reported in 5% to 10% of cases. METHODS: TRA-PCI failure was categorized as primary (clinical reasons) or crossover failure. Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed. RESULTS: From January to June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas 45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30 (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%); subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%) patients. Female sex (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.95 to 5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63 to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p = 0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0 to 7 predicted a TRA-PCI failure rate from 2% to 80%. CONCLUSIONS: In a high-volume radial center, 2.7% of patients undergoing PCI are excluded from initial TRA on clinical grounds, whereas crossover to femoral approach is required in only 1.8% of the cases. A new simple clinical risk score is developed to predict TRA-PCI failure.

The effects of an exercise and lifestyle intervention program on cardiovascular, metabolic factors and cognitive performance in middle-aged adults with type II diabetes: a pilot study.

BACKGROUND: Canada is experiencing a rise in type II diabetes mellitus (T2DM), a known risk factor for accelerated cognitive decline and dementia. Within the context of an aging population, this will impose significant individual and societal burden, making the development of prevention programs imperative. OBJECTIVE: This pilot study examines the effects of the Diabetes Exercise and Healthy Lifestyle Service, a 24-week intervention program, on cardiovascular, metabolic regulation and cognitive function in adults with T2DM. METHODS: Seventeen middle-aged participants provided blood samples for biological markers, underwent cognitive testing and a physical stress test pre- and post-intervention. Cognitive performance was evaluated using the California Verbal Learning Test (CVLT), Digit Symbol Substitution Tasl (DSST) and fluency test. RESULTS: Adjusted models reveal participants displayed increased cardiovascular fitness (VO2 peak: Mchange=4.09 mL∙kg∙min(-1) SE=1.4), peak heart rate (Mchange= 9.28 beats⋅min(-1) SE=2.68) and change in heart rate (Mchange=10.71 SE=1.76) in response to the stress test (ps<0.05) following the 24-week intervention. A decrease in body mass index (BMI) (Mchange= -1.03 SE=0.40) and depressive symptomatology (CES-D: Mchange = -3.62 SE=1.44) was also found (ps<0.05). No change was found for lipid and glucose levels. Surprisingly, analyses showed that cognitive performance on the CVLT immediate recall (M= -4.37 SE=2.21), CVTL short-delay recall (M= -1.06 SE=0.55), DSST (Mchange= -3 SE=0.53) and category fluency (Mchange= -1.69 SE=0.78) declined following the intervention (ps<0.05); however, decline on the CVLT was limited to adults with co-morbid T2DM and hypertension. CONCLUSION: Additional research is needed to evaluate the benefit of an exercise and lifestyle program that targets cognitive health in those with T2DM.

Telephone contact to improve adherence to dual antiplatelet therapy after drug-eluting stent implantation.

BACKGROUND: Many patients delay or interrupt dual antiplatelet therapy (DAT) after drug-eluting stent (DES) implantation, which increases the risk of stent thrombosis and death. OBJECTIVE: To test the hypothesis that simple telephone contact made by nurses would improve adherence to and persistence of DAT. DESIGN: Randomised controlled trial. PATIENTS AND INTERVENTION: A total of 300 patients (mean±SD 64±10 years, 73% male) were recruited immediately after DES implantation performed between June 2009 and June 2010. The last patient recruited reached the 1-year follow-up time point in June 2011. Patients were randomised to one of two groups: intervention, with four telephone follow-ups, versus a control group. In the intervention group, phone calls were made within 7 days of the DES implantation and at 1, 6 and 9 months to support drug adherence. Control patients were followed as per usual clinical practice. Pharmacy data were collected to assess drug prescription filling and refill. SETTING: Tertiary care university cardiovascular centre and community. MAIN OUTCOME MEASURES: The primary end point was the proportion of days covered with aspirin and clopidogrel over the year after discharge as assessed by pharmacy refill data. Secondary outcome measures included persistence of aspirin and clopidogrel treatment, defined as no gaps longer than 14 days during follow-up. RESULTS: Most patients (73%) underwent DES implantation in the context of an acute coronary syndrome. All patients had drug insurance cover, either from the public plan (59%) or through private plans (41%). Complete pharmacy follow-up data were available for 96% of the cohort. At 12 months, median scores (25th-75th centile) for adherence to aspirin and clopidogrel were 99.2% (97.5-100%) and 99.3% (97.5-100%), respectively, in the intervention group compared with 90.2% (84.2-95.4%) and 91.5% (85.1-96.0%), respectively, in the control group (p<0.0001 for aspirin and clopidogrel). Patients in the intervention group were significantly more persistent in the aspirin and clopidogrel treatment than those in the control group. For clopidogrel, 87.2% of patients in the intervention group were still persistent at 12 months compared with only 43.1% in the control group (p<0.0001). CONCLUSIONS: A simple approach of four telephone calls to patients after DES implantation significantly improved 1-year drug adherence to near-perfect scores. Persistence of DAT was also significantly improved by the intervention.

Effects of chronic sildenafil use on pulmonary hemodynamics and clinical outcomes in heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) in heart transplant (HT) candidates is associated with poor survival after HT. This study assessed the effect of peri-operative sildenafil administration on pulmonary hemodynamics and clinical outcomes in patients with advanced heart failure who were considered high-risk for HT because of elevated PVR and transpulmonary gradient (TPG). METHODS: The study included 119 consecutive patients who underwent HT between 2004 and 2011. Fifteen patients (Group A) had severe pulmonary hypertension (PH), defined as mean pulmonary pressure (MPAP)>25 mm Hg and PVR>2.5 Wood units (WU), and/or TPG>12 mm Hg after vasodilator test or the continuous administration of inotropics drugs, and 104 patients (Group B) were without severe PH. Group A received sildenafil therapy. Pulmonary hemodynamics were evaluated before HT with and without sildenafil therapy. Right catheterization was performed early after HT with sildenafil therapy and late after HT without sildenafil. Survival after HT was compared between the groups. RESULTS: The sildenafil dosage was 109±42 mg/day during 163±116 days before HT. After sildenafil therapy MPAP, PVR, and TPG decreased from 43.9±12.5 to 33.4±5.8 mm Hg, 5.0±1.1 to 3.0±1.6 WU, and 17.3±3.2 to 10.2±4.1 mm Hg, respectively (p<.01). All patients underwent successful HT. Sildenafil dosage was 140±70 mg/day for 43±45 days after HT. There were no differences in PVR and TPG with sildenafil therapy early after HT and without sildenafil 6 months after HT. Survival after HT was similar between the groups. CONCLUSION: Sildenafil therapy before and after HT in patients with severe PH is associated with improved pulmonary hemodynamics and successful HT, without an increase in post-HT mortality.

Acute heart failure: perspectives from a randomized trial and a simultaneous registry.

BACKGROUND: Randomized controlled trials (RCT) are limited by their generalizability to the broader nontrial population. To provide a context for Acute Study of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, we designed a complementary registry to characterize clinical characteristics, practice patterns, and in-hospital outcomes of acute heart failure patients. METHODS AND RESULTS: Eligible patients for the registry included those with a principal diagnosis of acute heart failure (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) from 8 sites participating in ASCEND-HF (n=697 patients, 2007-2010). Baseline characteristics, treatments, and hospital outcomes from the registy were compared with ASCEND-HF RCT patients from 31 Canadian sites (n=465, 2007-2010). Patients in the registry were older, more likely to be female, and have chronic respiratory disease, less likely to have diabetes mellitus: they had a similar incidence of ischemic HF, atrial fibrillation, and similar B-type natriuretic peptide levels. Registry patients had higher systolic blood pressure (registry: median 132 mm Hg [interquartile range 115-151 mm Hg]; RCT: median 120 mm Hg [interquartile range 110-135 mm Hg]) and ejection fraction (registry: median 40% [interquartile range 27-58%]; RCT: median 29% [interquartile range 20-40 mm Hg]) than RCT patients. Registry patients presented more often via ambulance and had a similar total length of stay as RCT patients. In-hospital mortality was significantly higher in the registry compared with the RCT patients (9.3% versus 1.3%,P<0.001), and this remained after multivariable adjustment (odds ratio 6.6, 95% CI 2.6-16.8, P<0.001). CONCLUSIONS: Patients enrolled in a large RCT of acute heart failure differed significantly based on clinical characteristics, treatments, and inpatient outcomes from contemporaneous patients participating in a registry. These results highlight the need for context of RCTs to evaluate generalizability of results and especially the need to improve clinical outcomes in acute heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

Deadly association of cardiogenic shock and chronic total occlusion in acute ST-elevation myocardial infarction.

BACKGROUND: The association between cardiogenic shock and 1 or >1 chronic total occlusion (CTO) in unselected patients presenting with ST-elevation myocardial infarction (MI) (STEMI) has not been characterized. METHODS: Patients with STEMI referred with or without cardiogenic shock were categorized into no CTO, 1 CTO, and >1 CTO. The primary end point was the 30-day mortality. RESULTS: Between 2006 and 2011, 2,020 consecutive patients were included. A total of 141 patients (7%) presented with cardiogenic shock on admission. The prevalence of 1 CTO and >1 CTO in a non-infarct-related artery was 23% and 5%, respectively, among patients with shock compared with 6% and 0.5% in patients without shock (P < .0001). Independent predictors of cardiogenic shock included left main-related MI (odds ratio [OR] 6.55, 95% CI 1.39-26.82, P = .019), CTO (OR 4.20, 95% CI 2.64-6.57, P < .001), creatinine clearance <60 mL/min (OR 3.41, 95% CI 2.32-4.99, P < .0001), and left anterior descending-related MI (OR 2.20, 95% CI 1.51-3.23, P < .0001). Thirty-day mortality was 100% in shock patients with >1 CTO, 65.6% with 1 CTO, and 40.2% in patients without CTO (P < .0001). After adjustment for left ventricular ejection fraction and renal function, CTO remained an independent predictor for 30-day mortality (hazard ratio [HR] 1.83; 95% CI 1.10-3.01, P = .02). CONCLUSION: In patients with STEMI, CTO was strongly associated with cardiogenic shock on admission. In this setting, mortality was substantially higher in patients with 1 CTO and exceedingly high in those with >1 CTO. The presence of CTO was an independent predictor of early mortality.

Assessment of dyspnea in acute decompensated heart failure: insights from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) on the contributions of peak expiratory flow.

OBJECTIVES: This study hypothesized that peak expiratory flow rate (PEFR) would increase with acute heart failure (AHF) treatment over the first 24 h, related to a Dyspnea Index (DI) change and treatment effect. BACKGROUND: Dyspnea is a key symptom and clinical trial endpoint in AHF, yet objective assessment is lacking. METHODS: In a clinical trial substudy, 421 patients (37 sites) underwent PEFR testing at baseline, 1, 6, and 24 h after randomization to nesiritide or placebo. DI (by Likert scale) was collected at hours 6 and 24. RESULTS: Patients were median age 70 years, and 34% were female; no significant differences between nesiritide or placebo patients existed. Median baseline PEFR was 225 l/min (interquartile range [IQR]: 160 to 300 l/min) and increased to 230 l/min (2.2% increase; IQR: 170 to 315 l/min) by hour 1, 250 l/min (11.1% increase; IQR: 180 to 340 l/min) by hour 6, and 273 l/min (21.3% increase; IQR: 200 to 360 l/min) by 24 h (all p < 0.001). The 24-h PEFR change related to moderate or marked dyspnea improvement by DI (adjusted odds ratio: 1.04 for each 10 l/min improvement [95% confidence interval (CI): 1.07 to 1.10]; p < 0.01). A model incorporating time and treatment over 24 h showed greater PEFR improvement after nesiritide compared with placebo (p = 0.048). CONCLUSIONS: PEFR increases over the first 24 h in AHF and could serve as an AHF endpoint. Nesiritide had a greater effect than placebo on PEFR, and this predicted patients with moderate/marked improvement in dyspnea, thereby providing an objective metric for assessing AHF. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852).

Importance of diffuse atherosclerosis in the functional evaluation of coronary stenosis in the proximal-mid segment of a coronary artery by myocardial fractional flow reserve measurements.

The objective of this study was to evaluate the impact of diffuse coronary atherosclerosis on the functional evaluation of moderate coronary lesions in the proximal-mid segment of a coronary artery and its clinical implications. This was a prospective study including 100 consecutive patients with a moderate lesion (45 ± 9% diameter stenosis) in the proximal-mid coronary segment who were evaluated with fractional flow reserve (FFR) measurement. No patient had any other angiographic stenosis distal to the evaluated coronary stenosis. FFR measurements were obtained just distal (~2 to 3 cm) to the lesion (FFR proximal measurement [FFR-PM]) and as distally as possible in the artery (FFR distal measurement [FFR-DM]) after administration of the same dose of intracoronary adenosine. Thirty-nine patients underwent dipyridamole or exercise myocardial single-photon emission computed tomography within 3 months of the FFR study. Mean FFR-PM was significantly higher compared to FFR-DM (0.84 ± 0.08 vs 0.78 ± 0.09, median gradient 0.06, 25th to 75th interquartile range 0.02 to 0.10, p <0.0001). FFR-DM was <0.75 in 33% of patients with FFR-PM ≥0.75, leading to the decision of revascularization in these patients. Performing FFR measurement in the left main/left anterior descending artery predicted a higher gradient between FFR-DM and FFR-PM (odds ratio 4.58, 95% confidence interval 1.4 to 15.03, p = 0.007). FFR-DM exhibited a better correlation with results of myocardial single-photon emission computed tomography compared to FFR-PM (kappa 0.33 vs 0.22, p <0.0001). In conclusion, significant differences between FFR-DM and FFR-PM were observed in patients with moderate coronary stenosis in the proximal-mid segment of a coronary artery, with FFR-DM exhibiting a better correlation with results of noninvasive functional tests. These differences influenced the treatment decision in about 1/3 of patients and highlight the potential clinical relevance of coronary pressure wire positioning for functional evaluation of lesions in the proximal-mid segment of the coronary arteries.

Effects of aspiration thrombectomy on necrosis size and ejection fraction after transradial percutaneous coronary intervention in acute ST-elevation myocardial infarction.

BACKGROUND: The use of routine aspiration thrombectomy in primary percutaneous coronary intervention (PCI) remains controversial. METHODS: Patients in the EArly Discharge after Transradial Stenting of CoronarY Arteries in Acute Myocardial Infarction (n = 105) study were treated with aspirin, clopidogrel, and abciximab within 6 hr of symptoms onset. Operators were allowed to use 6 Fr Export aspiration catheter at their discretion. In this observational analysis, we compared acute and late results in patients treated with and without thrombectomy using cardiac biomarkers, angiographic, cardiovascular magnetic resonance (CMR), and clinical parameters. RESULTS: Patients in the thrombectomy group (n = 44) had longer symptoms to balloon time (196 ± 86 min vs. 164 ± 62, P = 0.039) and higher incidence of preprocedural TIMI flow grade 0 or 1 (84% vs. 64%, P = 0.028). Following PCI, both groups had similar incidence of TIMI flow grade 3 (93 vs. 92%, P = 0.73) and myocardial blush grade 2 or 3 (80 vs. 77%, P = 0.86), respectively. Patients in thrombectomy group had significantly higher post-PCI maximum values of creatine kinase-MB (P = 0.0007) and troponin T (P = 0.0010). Accordingly, post-PCI myocardial necrosis by CMR was higher (P = 0.0030) in patients in the thrombectomy group. At 6-month follow-up, necrosis size remained higher (20.7% ± 13.3% vs. 13.5% ± 11.1%, P = 0.012) in the thrombectomy group. Ejection fraction at 6 months was 65% ± 9% in patients in thrombectomy group compared to 70% ± 11% in patients without (P = 0.070). Results were not affected by initial TIMI flow or symptoms to balloon time. Clinical events remained comparable in both groups at 12 months follow-up. CONCLUSION: In patients with ST-segment elevation myocardial infarction presenting within 6 hr of symptoms and undergoing primary angioplasty with maximal antiplatelet therapy, acute and late results did not suggest significant benefit for additional aspiration thrombectomy, irrespective of initial TIMI flow or total ischemic time.

Impact of thrombus aspiration on angiographic and clinical outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: Primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) may be limited by thrombus embolization. Export aspiration catheter (EAC) is a thrombectomy device which may enhance angiographic results, but its impact on clinical outcomes is unclear. This trial objective was to assess the impact of EAC on angiographic and clinical outcomes in patients with STEMI. METHODS: All STEMI patients undergoing primary or rescue PCI in a tertiary care center were included. Patients were divided in two groups according to the use of the EAC. Patients were followed up prospectively for death, reinfarction, revascularization, or stroke. Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit vessel was assessed before and after PCI. RESULTS: Included in the analysis were 535 patients. EAC was used in 165 patients before angioplasty (Group 1) and 370 patients underwent PCI without thrombus aspiration (Group 2). More patients in Group 1 had initial TIMI flow 0-1 compared to Group 2 (88% vs. 62%, P<.001). Proportion of patients with a final TIMI flow 3 was the same in both groups (89.1% vs. 87.6% for Groups 1 and 2, respectively; P=.67). An analysis restricted to patients with initial TIMI flow 0-1 yielded similar results. No difference in clinical outcomes was observed between the two groups (P=.70). CONCLUSIONS: Selective use of the EAC based on the judgment of operators results in excellent angiographic and clinical results. Further clinical investigation is needed to definitely answer whether thromboaspiration needs to be performed in all STEMI patients undergoing primary PCI.

Incidence, range, and clinical effect of hemoglobin changes within 24 hours after transradial coronary stenting.

Anemia and major bleeding are independent predictors of outcomes after acute coronary syndromes and percutaneous coronary intervention (PCI). Although the transradial approach reduces the incidence of bleeding, the hemoglobin changes after transradial PCI have not been defined. We serially assessed the hemoglobin values before and after transradial PCI and evaluated the effect of hemoglobin changes on outcomes. In the EArly Discharge After Transradial Stenting of CoronarY Arteries (EASY) trial, 1,348 patients underwent transradial PCI. All patients received aspirin, clopidogrel, and a bolus of abciximab before PCI. The hemoglobin values were assessed immediately before and 4 to 6 hours and 12 to 24 hours after PCI. The major adverse cardiac events (death, myocardial infarction, and target vessel revascularization) were assessed < or =3 years after PCI. According to the World Health Organization classification, 206 patients (15%) had anemia before PCI and 410 (30%) developed anemia within 24 hours after PCI. A mean hemoglobin decrease of 0.6 +/- 1.0 g/dl occurred within 24 hours after PCI. At 30 days, the major adverse cardiac events were significantly increased when the hemoglobin decrease within 24 hours after PCI was >3 g/dl (p = 0.0002). Patients with anemia within 24 hours after PCI had significantly more major adverse cardiac events at 30 days, 6 months, 1 year, and 3 years than patients without anemia (log-rank p = 0.0044). After adjustment for differences in the baseline characteristics, anemia within 24 hours after PCI remained an independent predictor of major averse cardiac events at 3 years (hazard ratio 1.30, 95% confidence interval 1.01 to 1.67, p = 0.045). In conclusion, within 24 hours after transradial PCI with maximal antiplatelet therapy, only a mild hemoglobin decrease was observed. The choice of a hemoglobin decrease >3 g/dl after PCI as a cutoff value for current definitions of major bleeding in modern PCI trials appears reasonable. Measures to prevent anemia and blood loss during PCI remain to be further studied.

Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance.

OBJECTIVES: The aim of this study was to determine whether a very early imaging strategy improves the prediction of late systolic dysfunction and poor outcomes in ST-segment elevation myocardial infarction (STEMI) compared with traditional predictors. BACKGROUND: Earlier prediction of poor outcomes after STEMI is desirable, because it will allow tailored therapy at the earliest possible time, when benefits might be greatest. METHODS: One hundred and three patients with acute STEMI were studied by contrast-enhanced cardiovascular magnetic resonance within 12 h of primary angioplasty and at 6 months and followed >2 years. The primary end point was left ventricular (LV) dysfunction, whereas poor outcomes were a key secondary end point. RESULTS: Traditional risk factors were only modest predictors of late LV dysfunction. Late gadolinium enhancement (LGE) volume maintained a stronger association to LV ejection fraction change than infarct transmurality, microvascular obstruction, or myocardial salvage during STEMI (p = 0.02). Multivariable logistic regression identified LGE volume during STEMI as the best predictor of late LV dysfunction (odds ratio: 1.36, p = 0.03). An LGE >or=23% of LV during STEMI accurately predicted late LV dysfunction (sensitivity 89%, specificity 74%). The LGE volume provided important incremental benefit for predicting late dysfunction (area under the curve = 0.92, p or=23% carried a hazard ratio of 6.1 for adverse events (p < 0.0001). CONCLUSIONS: During the hyperacute phase of STEMI, LGE volume provides the strongest association and incremental predictive value for late systolic dysfunction and discerns poor late outcomes.

Improving myocardial salvage in late presentation acute ST-elevation myocardial infarction with proximal embolic protection.

BACKGROUND: Late-presenting ST-elevation myocardial infarction (STEMI) patients possess larger, more organized coronary thrombus leading to greater ventricular remodeling and arrhythmia despite angioplasty and pharmacological therapies. We hypothesized that myocardial injury would be reduced in late STEMI by proximal embolic protection (PEP). METHODS: 31 patients with first STEMI 12-24 hr after pain onset and TIMI 0-1 flow were treated with or without PEP (cohort design matched for age, gender, and infarct-related artery). Contrast-enhanced magnetic resonance determined myocardial function, area at risk, necrosis, salvaged myocardium, and arrythmogenic peri-infarct region. Clinical follow-up was performed. RESULTS: Pain to balloon time was 18 hr (95% CI 15.5-21.2 h), and Q waves were present in 87%. Angioplasty was performed with PEP in 15 and without in 16. Left ventricular (LV) volumes and ejection fraction were similar (EF 46.9% vs. 49.0% without PEP, P = 0.9). Although myocardial necrosis was similar (32.5 vs. 37.3% of LV, P = 0.3), PEP improved microvascular obstruction (8.7 vs. 11.2% of LV, P = 0.02) salvaged myocardium (39.6% vs. 29.6% of area at risk, P = 0.001), and the peri-infarct region (20.9 vs. 29.6% of infarct, P < 0.0001). On multivariate analysis, the use of PEP was an independent predictor of decreased arrythmogenic peri-infarct region and greater myocardial salvage. CONCLUSION: In this pilot study, PEP improved myocardial salvage and the arrythmogenic peri-infarct region in late-presentation STEMI. Randomized trials are required to assess the clinical impact of improving salvaged myocardium and the peri-infarct region with PEP.

Intracoronary compared to intravenous Abciximab and high-dose bolus compared to standard dose in patients with ST-segment elevation myocardial infarction undergoing transradial primary percutaneous coronary intervention: a two-by-two factorial placebo-controlled randomized study.

Platelet aggregation inhibition (PAI) of > or =95% has been associated with improved outcomes after percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitor treatment. A greater thrombotic burden in acute ST-segment elevation myocardial infarction (STEMI) might require higher doses and/or intracoronary delivery of glycoprotein IIb/IIIa inhibitors to achieve optimal PAI. Using a 2 x 2 factorial placebo-controlled design, 105 patients with STEMI who had been referred for primary PCI within 6 hours of symptom onset were randomized to intracoronary (IC) or intravenous (IV) delivery of an abciximab bolus at a standard dose (0.25 mg/kg) or high dose (> or =0.30 mg/kg) of abciximab. The primary end point was PAI measured at 10 minutes after the bolus of abciximab. Secondary end points included the acute and 6-month outcomes using angiographic parameters, cardiac biomarkers, cardiovascular magnetic resonance imaging, and clinical end points. At 10 minutes after the bolus, the proportion of patients with > or =95% PAI was not different between the IC and IV groups (53% vs 54%, p = 1.00) nor between the high-dose and standard-dose bolus groups (56% vs 51%, p = 0.70). Acutely, the angiographic myocardial blush grades, peak release of cardiac biomarkers, necrosis size, myocardial perfusion, and no reflow as assessed by magnetic resonance imaging, and clinical end points were similar between the groups and did not suggest a benefit for IC compared to IV or high-dose versus standard-dose bolus of abciximab. No increase occurred in bleeding complications with the high-dose bolus or IC delivery. The clinical, angiographic and cardiac magnetic resonance imaging outcomes at 6 and 12 months were similar between the 4 groups. In conclusion, in patients with STEMI presenting with symptom onset <6 hours and undergoing transradial primary PCI, PAI remained suboptimal, despite a higher dose bolus of abciximab. A higher dose bolus or IC delivery of abciximab bolus was not associated with improved acute or late results compared to the standard IV dosing and administration.

Percutaneous versus surgical delivery of autologous myoblasts after chronic myocardial infarction: an in vivo cardiovascular magnetic resonance study.

BACKGROUND: Stem cell transplantation for chronic myocardial infarction (MI) provides variable benefits. Most clinical trials have relied on surgical delivery, where results are biased by simultaneous coronary bypass. When bypass is not indicated, percutaneous delivery may provide comparable efficacy with reduced risk. We evaluated in vivo by cardiovascular magnetic resonance (CMR) the effects of autologous myoblast (AM) transplantation on myocardial morphology, function, perfusion and scar, and compared percutaneous versus surgical delivery. METHODS: Chronic MI was completed in 10 Yucatan mini-pigs. Three months later, AM were injected in half by percutaneous NOGA(R) system and in the other half by surgical mini-thoracotomy. CMR was performed at baseline and 6 months after transplantation. RESULTS: Six months after injection, AM transplantation led to a 26.3% decrease in indexed left ventricular end-diastolic volume (95% CI: 20.1-29.7%; P = 0.02), 25.5% thickening of the infarct-related segment (IRS) wall (95% CI: 19.6-33.2%; P = 0.03), and 20.9% increase in left ventricle (LV) ejection fraction (95% CI: 15.8-28.4%; P = 0.03). Scar tissue within IRS decreased by 29.4% (95% CI: 19.2-37.0%; P = 0.03), whereas the number of nonviable segments decreased by 25.0% (95% CI: 16.4-32.6%; P = 0.04). Myocardial perfusion of IRS improved by 29.1% (95% CI: 19.7-36.1%; P = 0.04). The arrhythmogenic peri-infarct zone increased by 33.2% (95% CI: 21.4-44.1%; P = 0.01) after AM transplantation. Benefits were similar by percutaneous or by surgical delivery. CONCLUSIONS: Comprehensive in vivo CMR reveals reversed remodeling and improved systolic function, perfusion, and scar characteristics after AM transplantation. A relative increase in the arrhythmogenic peri-infarct border zone may explain previously reported arrhythmia. Percutaneous and surgical transplantation of AM both lead to comparable improvements in chronic MI.