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OBJECTIVE: To reanalyze the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial using a new composite cardiovascular disease (CVD) outcome to determine how best to treat patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD). METHODS: From January 1, 2001 to November 30, 2008, 2,368 T2DM patients with angiographically defined CAD were randomly assigned to insulin sensitizing (IS) or insulin providing (IP) therapy and simultaneously to coronary revascularization (REV) versus no or delayed revascularization (MED) with all patients receiving intensive medical treatment. The outcome for this analysis was a composite of eight CVD events. RESULTS: Four-year composite CVD outcome Kaplan-Meier rates were 35.8% (95% CI: 33.1–38.5%) with IS versus 41.6% (38.7–44.5%) with IP (P=.004). Most of this difference was associated with lower in-trial levels of fibrinogen, c-reactive protein, and hemoglobin A1c (HbA1c) with IS. Four-year composite CVD rates were 32.7% (30.0–35.4%) with REV versus 44.7% (41.8–47.6%) with MED (P

Background The optimal coronary revascularization strategy in patients with stable ischemic heart disease (SIHD) who have type 2 diabetes (T2DM) and chronic kidney disease (CKD) remains unclear. Objectives This patient-level pooled analysis sought to compare outcomes of 3 large, federally-funded randomized trials in SIHD patients with T2DM and CKD (COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation], BARI 2D [Bypass Angioplasty Revascularization Investigation 2 Diabetes], and FREEDOM [Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multi-vessel Disease]). Methods The primary endpoint was the composite of major adverse cardiovascular or cerebrovascular events (MACCE) including all-cause death, myocardial infarction (MI), or stroke adjusted for trial and randomization strategy. Results Of the 4,953 patients with available estimated glomerular filtration rate (eGFR) at baseline, 1,058 had CKD (21.4%). CKD patients were more likely to be older, be female, and have a history of heart failure. CKD subjects were more likely to experience a MACCE (adjusted hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28 to 1.71; p = 0.0001) during a median 4.5-year follow-up. Both mild (eGFR 45 to 60 ml/min/1.73 m2) and moderate to severe (eGFR Conclusions Among SIHD patients with T2DM and no CKD, CABG + OMT significantly reduced MACCE compared with PCI + OMT. In subjects with CKD, there was a nonsignificant trend toward a better MACCE outcome with CABG and a significant reduction in subsequent revascularization.

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women’s Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1–5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow‐up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow‐up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05–2.17], P =0.03; 1–5 days: HR [95% CI], 1.02 [0.75–1.39], P =0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33–2.35], P Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female‐specific CVD risk factor.

Introduction: Ischemic heart disease is the leading cause of death worldwide. It is unknown whether initial revascularization using percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) plus optimal medical therapy (OMT) in patients with chronic coronary syndromes (CCS), obstructive coronary artery disease (CAD) and myocardial ischemia improves hard clinical outcomes compared to OMT alone. Hypothesis: In CCS patients with obstructive CAD and documented myocardial ischemia, initial revascularization plus OMT does not reduce death or nonfatal myocardial infarction (MI) compared to OMT alone. Methods: We searched Ovid Medline, Embase, Scopus, and Cochrane Library databases from inception to March 2020 for randomized controlled trials (RCTs) of PCI or CABG and OMT vs OMT alone for CCS patients in whom stents and statins were used in more than 50% of patients. Random-effects models were used to estimate average treatment effects across trials. The co-primary outcomes were all-cause death and nonfatal MI at 5 years. Results: Six RCTs were identified that randomized 10,020 CCS patients. At 5 years, among 5,025 CCS patients assigned to revascularization plus OMT, there were 492 deaths (9.8%) compared to 482 deaths among 4,995 patients (9.6%) assigned to OMT (OR, 1.01, 95% CI: 0.88-1.16; P=0.87). There were 521 nonfatal MIs (10.3%) in those assigned to revascularization plus OMT compared with 593 MIs (11.9%) in those assigned to OMT arms (OR, 0.78, 95% CI: 0.58-1.05; P=0.10). In subgroup analysis, nonfatal MI was not reduced by PCI plus OMT (OR, 0.95, 95% CI: 0.74-1.23, P=0.71) but was significantly reduced in studies of CABG plus OMT compared to OMT alone (OR, 0.38, 95% CI: 0.23-0.64, P Conclusions: In patients with CCS and myocardial ischemia, initial revascularization with PCI or CABG plus OMT was not associated with a reduction in death at 5 years compared to OMT alone. CABG plus OMT reduced nonfatal MI compared to OMT alone whereas PCI did not. These findings suggest important differences in MI outcomes between those who undergo CABG vs. PCI, but no overall difference in mortality compared with OMT alone.

Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased cardiovascular events, especially in high-risk populations.This study sought to evaluate the influence of LDL-C on the incidence of cardiovascular events either following a coronary revascularization procedure (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or optimal medical therapy alone in patients with established coronary heart disease and type 2 diabetes (T2DM).Patient-level pooled analysis of 3 randomized clinical trials was undertaken. Patients with T2DM were categorized according to the levels of LDL-C at 1 year following randomization. The primary endpoint was major adverse cardiac or cerebrovascular events ([MACCE] the composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke).A total of 4,050 patients were followed for a median of 3.9 years after the index 1-year assessment. Patients whose 1-year LDL-C remained ≥100 mg/dl experienced higher 4-year cumulative risk of MACCE (17.2% vs. 13.3% vs. 13.1% for LDL-C between 70 and 100 mg/dl and LDL-C 70 mg/dl, respectively; p = 0.016). When compared with optimal medical therapy alone, patients with PCI experienced a MACCE reduction only if 1-year LDL-C was 70 mg/dl (hazard ratio: 0.61; 95% confidence interval: 0.40 to 0.91; p = 0.016), whereas CABG was associated with improved outcomes across all 1-year LDL-C strata. In patients with 1-year LDL-C ≥70 mg/dl, patients undergoing CABG had significantly lower MACCE rates as compared with PCI.In patients with coronary heart disease with T2DM, lower LDL-C at 1 year is associated with improved long-term MACCE outcome in those eligible for either PCI or CABG. When compared with optimal medical therapy alone, PCI was associated with MACCE reductions only in those who achieved an LDL-C 70 mg/dl.

Background and aims The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed. Methods We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T2DM randomized to optimal medical therapy [OMT], percutaneous coronary intervention [PCI] + OMT, or coronary artery bypass grafting [CABG] + OMT. Endpoints were death/myocardial infarction (MI)/stroke, post-randomization revascularization (both over 5 years), and angina control at 1 year. Results Increasing severity of baseline angina was associated with higher rates of death/MI/stroke (p = 0.009) and increased need for post-randomization revascularization (p = 0.001); after multivariable adjustment, only association with post-randomization revascularization remained significant. Baseline angina severity did not influence the superiority of CABG + OMT to reduce the rate of death/MI/stroke and post-randomization revascularization compared to other strategies. CABG + OMT was superior for angina control at 1 year compared to both PCI + OMT and OMT alone but only in patients with ≥ Class II severity at baseline. Comparisons between PCI + OMT and OMT were neutral except that PCI + OMT was superior to OMT for reducing the rate of post-randomization revascularization irrespective of presenting angina severity. Conclusions Presenting angina severity did not influence the superiority of CABG + OMT with respect to 5-year rates of death/MI/stroke and need for post-randomization revascularization. Presenting angina severity minimally influenced relative benefits for angina control at 1 year.

Objectives To evaluate the effectiveness of wheelchair assessment and configuration on pressure injury incidence, mobility, and functioning in a wheelchair. Design Randomized controlled trial with participants individually randomized into intervention and control groups. Setting Nursing home. Participants Nursing home residents aged 60 and older who used wheelchairs and were at risk for pressure injuries (N=258). Intervention Treatment and evaluation, individually configured wheelchair and skin protection cushion; control and evaluation, facility-provided wheelchair and skin protection cushion. Measurements Pressure injury incidence, Nursing Home Life Space Diameter score, Functioning Every Day in a Wheelchair-Capacity (FEW-C) score, and Wheelchair Skills Test (WST) score. Results No differences in pressure injuries (p=.77) were found. Pelvic rotation (odds ratio (OR)=0.15, 95% confidence interval (CI)=0.03-0.70, p=.02) and Day 14 WST skill score (OR=0.74, 95% CI=0.60-0.91, p=.004) were significant predictors of pressure injuries. Significant differences were observed between groups in change in FEW-C independence scores between before randomization and endpoint (p=.03) and before randomization and 14 days (p=.04). Conclusion Participants with individually configured wheelchairs improved more in the safe and effective use of their wheelchairs than residents with facility-provided wheelchairs. The outcomes indicated that nursing home residents functioned safely at a higher level in their wheelchairs if their devices were individually configured using a comprehensive wheelchair and seating assessment process. There was no difference in the incidence of pressure injuries between the two groups. Trial registration NCT01275313.

To evaluate the effectiveness of wheelchair assessment and configuration on pressure injury incidence, mobility, and functioning in a wheelchair.Randomized controlled trial with participants individually randomized into intervention and control groups.Nursing home.Nursing home residents aged 60 and older who used wheelchairs and were at risk for pressure injuries (N=258).Treatment and evaluation, individually configured wheelchair and skin protection cushion; control and evaluation, facility-provided wheelchair and skin protection cushion.Pressure injury incidence, Nursing Home Life Space Diameter score, Functioning Every Day in a Wheelchair-Capacity (FEW-C) score, and Wheelchair Skills Test (WST) score.No differences in pressure injuries (p=.77) were found. Pelvic rotation (odds ratio (OR)=0.15, 95% confidence interval (CI)=0.03-0.70, p=.02) and Day 14 WST skill score (OR=0.74, 95% CI=0.60-0.91, p=.004) were significant predictors of pressure injuries. Significant differences were observed between groups in change in FEW-C independence scores between before randomization and endpoint (p=.03) and before randomization and 14 days (p=.04).Participants with individually configured wheelchairs improved more in the safe and effective use of their wheelchairs than residents with facility-provided wheelchairs. The outcomes indicated that nursing home residents functioned safely at a higher level in their wheelchairs if their devices were individually configured using a comprehensive wheelchair and seating assessment process. There was no difference in the incidence of pressure injuries between the two groups.NCT01275313.

Diabetic medications can cause hypoglycemia, which may lead to myocardial damage.This study sought to determine whether hypoglycemia is associated with higher levels of high-sensitivity cardiac troponin T (hsTnT).The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial randomized patients with type 2 diabetes mellitus and stable coronary artery disease, and closely followed them for hypoglycemia over the first year. Hypoglycemia was classified by maximum severity and frequency. hsTnT was measured at baseline and 1 year, and analyzed using multivariable regression.Of 1,984 patients, follow-up hypoglycemia was absent in 1,026 (52%) patients, mild in 875 (44%), and severe in 83 (4%), and occurred less than weekly in 561 (28%) and greater than or equal to weekly in 397 (20%). hsTnT levels were associated with hypoglycemia: a median of 11.4 ng/l (interquartile range [IQR]: 8.1 to 17.3 ng/l) for none, 12.5 ng/l (IQR: 8.3 to 19.3 ng/l) for mild, and 13.7 ng/l (IQR: 9.9 to 24.9 ng/l) for severe hypoglycemia (p = 0.0001); and 12.5 ng/l (IQR: 8.3 to 18.1 ng/l) for less than weekly and 13.0 ng/l (IQR: 8.8 to 21.1 ng/l) for greater than or equal to weekly hypoglycemia (p = 0.0013). Severe hypoglycemia was associated with 34% higher 1-year hsTnT levels (p 0.0001) in unadjusted analysis, 17% higher (p = 0.006) after adjustment for baseline factors unrelated to diabetes, and 6% higher (p = 0.23) after further adjustment for the duration and severity of diabetes. Hypoglycemia greater than or equal to weekly was associated with 14% higher hsTnT (p = 0.0003) in unadjusted analysis, 12% higher (p = 0.0002) after adjustment for baseline factors unrelated to diabetes, and 4% higher (p = 0.16) after adjustment for diabetes related factors.Hypoglycemia was associated with elevated hsTnT levels, but this may be due to more severe diabetes in patients who developed hypoglycemia, rather than the direct result of hypoglycemia. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI2D]; NCT00006305).

Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups.Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3326 patients who underwent PCI with DES versus BMS were evaluated.With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25-0.69, p0.001) and whites (aHR=0.67, 95% CI 0.51-0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60-0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39-1.13, p=0.13).The use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents.

Cardiac troponin is the preferred marker of myocardial necrosis in patients with suspected myocardial infarction (MI). Increasingly sensitive assays have allowed the detection of very low circulating troponin concentrations in ambulatory patients, and these low troponin levels are strong

Background In a previous study, we found that a biomarker risk score ( BRS ) comprised of C‐reactive protein, fibrin‐degradation products, and heat shock protein‐70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS , and (3) elucidate whether an altered BRS parallels altered risk. Methods and Results Two thousand thirty‐two subjects with coronary artery disease were followed for 5.3±1.1 years for cardiovascular events. Biomarkers were measured at baseline and retested in 1304 subjects at 1 year. BRS was determined as the biomarker number above previously defined cut‐off values (C‐reactive protein >3 mg/L, heat shock protein‐70 >0.313 ng/mL, and fibrin‐degradation products >1 μg/mL). After adjustment for covariates, those with a BRS of 3 had a 4‐fold increased risk of all‐cause death and a 6.8‐fold increased risk of cardiac death compared with those with a BRS of 0 (95% CI , 2.9–16.0; P BRS . BRS recalibrated at 1 year also predicted risk. Those with 1‐year BRS of 2 to 3 had a 4‐year mortality rate of 21.1% versus 7.4% for those with BRS of 0 to 1 ( P Conclusions Our results validate the ability of the BRS to identify coronary artery disease patients at very high near‐term risk of myocardial infarction/death. After 1 year of intensive medical therapy, the BRS decreased significantly, and the reclassified BRS continued to track with risk. Our results suggest that repeated BRS measurements might be used to assess risk and recalibrate therapy.

Background Low respiratory hygiene compliance among health care workers of emergency departments has become a major concern in the spread of respiratory infections. Our objective was to determine the compliance with respiratory hygiene of triage nurses at 2 university hospital centers and to identify factors influencing compliance to the respiratory hygiene principles of emergency health care workers. Methods A 2-part, cross-sectional, descriptive study was conducted at 2 training centers. An anonymous observation of compliance with respiratory hygiene by triage emergency nurses was performed. A self-administered, voluntary questionnaire on attitudes, perceptions, and knowledge of respiratory hygiene guidelines was distributed to the health care workers at the emergency department of the 2 hospital sites. Results Median objective compliance with respiratory hygiene measures of triage nurses was 22% (interquartile range [IQR], 11%-33%). Median perceived compliance of the health care workers was 68% (IQR, 61%-79%). Median actual knowledge score was 75% (IQR, 75%-100%). Overall, 91.9% of respondents believed that the mask was an effective preventive measure. The main obstacles toward mask wearing by the health care worker were "tendency to forget" (37.8%) and "discomfort" (35.1%). Conclusion The compliance rate at our institution is very low. We identified a few factors affecting adherence to respiratory hygiene measures that are of potential use in targeting groups and formulating recommendations.

Background— Women Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated the association of sex and age on cardiovascular-related outcomes in10 963 patients (3797 women, 394 P =0.003), driven largely by higher rates of repeat revascularizations for target vessel or target lesion failure (coronary artery bypass graft surgery: 8.9% versus 3.9%, P P =0.005, adjusted hazard ratio 1.6, 95% confidence interval 1.2–2.2). At 5 years, young women remained at higher risk for repeat procedures (coronary artery bypass graft surgery: 10.7% versus 6.8%, P =0.04, adjusted hazard ratio 1.71, 95% confidence interval 1.01–2.88; repeat PCI [target vessel]: 19.7% versus 11.8%, P =0.002, adjusted hazard ratio 1.8, 95% confidence interval 1.24–2.82). Compared with older women, younger women remained at increased risk of major adverse cardiovascular events, whereas all outcome rates were similar in older women and men. Conclusions— Young women, despite having less severe angiographic coronary artery disease, have an increased risk of target vessel and target lesion failure. The causes of this difference deserve further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00005677.

The effectiveness and safety of drug-eluting stents (DES) compared with bare-metal stents (BMS) in saphenous vein graft (SVG) disease remains unclear. In particular, there is a paucity of data on long-term outcomes. In this study, 395 patients enrolled in the National Heart, Lung, and Blood Institute Dynamic Registry who underwent stenting of SVG lesions with BMS (n = 192) from 1999 to 2006 or DES (n = 203) from 2004 to 2006 were analyzed. Patients were followed prospectively for the occurrence of cardiovascular events and death at 3 years. Patients treated with DES were more likely to have diabetes mellitus and other co-morbidities and previous percutaneous coronary intervention. Treated lesions in DES patients were more complex than those in BMS patients. At 3 years of follow-up, the adjusted risk for target vessel revascularization (hazard ratio 1.03, 95% confidence interval 0.65 to 1.62, p = 0.91) and death or myocardial infarction (hazard ratio 0.72, 95% confidence interval 0.49 to 1.04, p = 0.08) was similar in patients treated with DES and those treated with BMS. The combined outcome of death, myocardial infarction, or target vessel revascularization excluding periprocedural myocardial infarction was also similar (adjusted hazard ratio 0.82, 95% confidence interval 0.62 to 1.09, p = 0.16). In conclusion, this multicenter nonrandomized study of unselected patients showed no benefit of DES in SVG lesions, including no reduction in target vessel revascularization, compared with BMS at 3 years. An adequately powered randomized controlled trial is needed to determine the optimal stent type for SVG percutaneous coronary intervention.

Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES ( n =677) and PES ( n =328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P =0.20), death and myocardial infarction (14.9% versus 13.6%, P =0.55), repeat revascularization (14.8% versus 17.8%, P =0.36), and stent thrombosis (1.3% versus 1.3%, P =0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

RATIONALE: Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES: We aimed to build on previous models by collating existing reference data in young children (aged 3-7 years), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS: The Asthma UK Collaborative initiative was established to collate lung function data from healthy young children aged 3-7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (Lambda-Mu-Sigma) method and extend previously published equations down to 3 years of age. MAIN RESULTS: The Asthma UK centiles charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n=3777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated dataset reflects a variety of equipment, measurement protocols and population characteristics and may be generalizable across different populations. CONCLUSIONS: We present prediction equations for spirometry for preschool children and provide a foundation which will facilitate continued updating.

Objectives This study sought to evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with insulin- and noninsulin-treated diabetes. Background Diabetes is a powerful predictor of adverse events after percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. The DES are efficacious among patients with diabetes; however, their safety and efficacy, compared with BMS, among insulin-treated versus noninsulin-treated diabetic patients is not well established. Methods Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n = 817) and noninsulin-treated (n = 1,749) patients with diabetes who underwent PCI with DES versus BMS. Results The use of DES, compared with BMS, was associated with a lower risk for repeat revascularization for both noninsulin-treated patients (adjusted hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.45 to 0.76) and insulin-treated subjects (adjusted HR = 0.63, 95% CI 0.44 to 0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or myocardial infarction (adjusted HR = 0.75, 95% CI 0.58 to 0.96). However, this benefit was confined to the population of noninsulin-treated patients (adjusted HR = 0.57, 95% CI 0.41 to 0.81). Among insulin-treated patients, there was no difference in death or myocardial infarction risk between DES- and BMS-treated patients (adjusted HR = 0.95, 95% CI 0.65 to 1.39). Conclusions Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin- or noninsulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared with BMS. These findings suggest that DES should be the preferred strategy for diabetic patients.

Objectives We investigated the effectiveness and safety of drug-eluting stents (DES) as used in routine clinical practice. Background Randomized trials have shown that DES prevent target vessel revascularization in selected patients, but whether this translates into superior outcomes, compared with bare-metal stents (BMS), for the full spectrum of patients treated with DES in North America is unknown. Methods Patients in the National Heart, Lung, and Blood Institute Dynamic Registry enrolled in 2004 who received at least 1 DES (n = 1,460) were compared with 1,763 patients enrolled in the recruitment period immediately preceding the approval of DES (2001 to 2002) who received at least 1 BMS. Results Patients receiving DES more often had diabetes mellitus and less often presented with an acute myocardial infarction (MI). At 1 year, cumulative death and MI was 7.6% in DES- and 8.7% in BMS-treated patients (adjusted hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.68 to 1.15; p = 0.34). The 1-year rate of target vessel revascularization was 5.0% in DES and 9.2% in BMS patients (p Conclusions The generalized use of DES resulted in better outcomes than BMS, with fewer clinically driven revascularization procedures and similar rates of death and MI at 1 year.

Patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) are increasingly being treated with percutaneous coronary intervention (PCI) and we sought to determine risk of adverse outcomes by type of MI. Patients enrolled in the National Heart, Lung, and Blood Institute Dynamic Registry from 1999 to 2004 who presented with an acute MI as an indication for PCI were studied. Baseline data and in-hospital and 1-year outcomes were compared based on ST-segment elevation (STEMI, n = 903; NSTEMI, n = 583) at presentation. Patients with STEMI were younger, had fewer co-morbidities, and had less extensive coronary artery disease than did patients with NSTEMI. Angiographic success and periprocedural complications were similar by MI type. In-hospital coronary artery bypass grafting, stroke, bleeding and recurrent MI were similar but mortality was higher in patients with STEMI (4.0% vs 1.4%, p = 0.004). Cardiogenic shock was associated with the greatest risk of in-hospital death (odds ratio 26.7, 95% confidence interval 11.4 to 62.3, p = 0.0001), but STEMI was also independently predictive of mortality. At 1 year, there was no influence of MI type on outcome. Age, cardiogenic shock, renal disease, peripheral vascular disease, and cancer were predictive of death and MI. Multivessel disease and a larger number of >50% lesions were associated with the need for repeat revascularization. In conclusion, STEMI was associated with a higher likelihood of in-hospital death than was NSTEMI, but long-term outcomes after PCI were independent of MI type. At 1 year, associated co-morbidities were strongly associated with death and MI, whereas only angiographic characteristics predicted the need for repeat revascularization.

Gender-based outcomes have not been evaluated in unselected patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). We investigated whether gender influences the relative safety and efficacy of DESs compared with bare metal stents (BMSs) in routine clinical practice. Using the National Heart, Lung, and Blood Institute Dynamic Registry, in-hospital and 1-year outcomes were stratified by gender in patients who receivedor =1 DES (486 women, 974 men) or BMS (631 women, 1,132 men). There were significant baseline differences by gender, including older age and a higher prevalence of co-morbidities in women and more previous coronary artery disease in men. There were no gender-related differences in in-hospital myocardial infarction, coronary artery bypass grafting, and death in those treated with BMSs or DESs. Antiplatelet use and stent thrombosis (1.3% of women vs 1.2% of men, p = 0.85) were similar at 1 year with DESs. At 1 year, patients with DESs had a lower rate of repeat PCI (14.1% in women vs 9.5%, p = 0.02; 12.0% in men vs 8.8%, p = 0.02). Adjusted 1-year outcomes in patients with BMSs and DESs, including death and myocardial infarction, were independent of gender. Use of DESs was the only factor, other than age, that conferred a lower risk for the need for repeat PCI in women (relative risk 0.61, 95% confidence interval 0.41 to 0.89, p = 0.01) and men (relative risk 0.68, 95% confidence interval 0.51 to 0.91, p = 0.001). In conclusion, the widespread use of DESs is safe and has decreased clinically driven revascularization compared with BMSs equally in women and men.

Forced expiratory maneuvers are routinely used in children, 6 years of age and older for the diagnosis and follow-up of respiratory diseases. Our objective was to establish normative data for an extensive number of parameters measured during forced spirometry in healthy 3- to 5-year-old children. Children aged between 3 and 5 years were tested in 11 daycare centers. Usual parameters, including FEV1, FVC, PEF, FEF(25-75), FEF25, FEF50, FEF75, and Aex were measured and analyzed in relation to sex, age, height, and weight. In addition, the same analysis was performed for FEV0.5 and FEV0.75. One hundred sixty-four children were recruited for testing including 87 girls and 77 boys. Thirty-five were 3 years old, 63 were 4 years old, and 66 were 5 years old. Overall, 143 children (87%) accepted to perform the test and 128 children (78%) were able to perform at least two technically acceptable expiratory maneuvers. Analyses using different regression models showed that height was the best predictor for every parameter. In conclusion, the present study confirms that most healthy 3-5 years old children can perform valid forced expiratory maneuvers. In agreement with other studies, we found that height is the most important single predictor of various parameters measured on forced spirometry. The present study is the first to establish normative values for FEV0.75, as well as to demonstrate that Aex can be easily performed in the majority of children aged 3-5 years. These are likely important parameters of lung function in this age range.

BACKGROUND: Technical factors relating to processing viscid sputum in cystic fibrosis (CF) and their influence on the reproducibility and validity of cell counts need to be evaluated. In addition, the methods need to be standardized so that they can be applied clinically and in research.OBJECTIVE: To examine the efficiency, reliability and validity of processing small volumes of spontaneously expectorated sputum from subjects with CF.METHODS: Sputum was collected from adults with CF (n=35) and compared with sputum from adults with infective bronchitis or bronchiectasis (IB/B) (n=16), or with asthma or chronic obstructive pulmonary disease (AS/COPD) (n=25). Selected sputum (100 mg to 200 mg) was processed with dithiothreitol (0.1%) and filtered. Total cell count (TCC) and viability were obtained in a counting chamber and cytospins were prepared and stained with Wright’s for a differential cell count. Sputum and filter remnant were processed for TCC, viability and differential cell count, and the efficiency was determined by comparing the mean loss in cell yield to the filter. Two different portions from the same sputum sample were processed for cell counts to determine reproducibility. Results were compared with those from IB/B and AS/COPD groups.RESULTS: Efficiency of cell dispersal was excellent and similar to that in AS/COPD and IB/B groups. Reproducibility of cell counts from two portions of a sputum sample was high (R≥0.80). CF sputum demonstrated a raised TCC and neutrophilia similar to IB/B but significantly higher than AS/COPD.CONCLUSION: The selection method of evaluating cell counts in viscid CF sputum is efficient, reproducible and valid.

Introduction: The benefits of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have been evaluated in patients with Type 2 Diabetes Mellitus (T2DM) and stable coronary artery disease (CAD) but analyses have not been stratified by detailed angiographic CAD burden or left ventricular ejection fraction (LVEF). Methods: A patient-level meta-analysis was undertaken among T2DM patients enrolled in COURAGE, BARI 2D and FREEDOM to assess the impact of randomization to OMT, PCI + OMT, or CABG + OMT on a composite end-point of Death/MI/Stroke and stratified by LVEF (≥ 50%, < 50%), 1, 2 or 3 vessel disease (VD) (% diameter stenosis ≥ 50%) and presence or absence of proximal left anterior descending (pLAD) disease. Hazard ratios (HR) for treatment groups were calculated from Cox regression models including all patients adjusting for trial and revascularization stratum in BARI 2D. Multivariable adjustment for risk factors was performed as a sensitivity analysis. Results: There were 5,034 patients included in the analysis (BARI 2D: n=2,368, COURAGE: n=766, FREEDOM: n=1,900) of whom 17% had LVEF < 50%, 29% had pLAD, and 77% had 2 or 3 VD. A total of 1,591 patients were randomized to OMT alone, 2,118 to PCI + OMT, and 1,325 to CABG + OMT. There were 1,116 events during a median 4.5 year follow-up. There was no significant effect on outcomes with OMT vs PCI + OMT irrespective of LVEF, presence/absence of pLAD and number of VD. By contrast, CABG + OMT significantly reduced the risk of Death/MI/Stroke in patients with 2 or 3 VD, irrespective of LVEF and presence/absence of pLAD (see Table). Results were similar with multivariable adjustment. Conclusions: In patients with T2DM and stable CAD, OMT alone appears to be as effective as PCI + OMT while CABG + OMT significantly reduces cardiovascular events in those with multivessel CAD, irrespective of LVEF or presence of pLAD.

There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF).This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement.A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy.Among 5,034 subjects, 15% had LVEF 50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT.CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has a lower success rate than PCI for non-CTO lesions. We sought to determine trends in the treatment of CTOs within the current interventional era. Using 4 sequential recruitment waves of the National Heart, Lung, and Blood Institute Dynamic Registry, we assessed the relative prevalence and success rates in treating CTO (n=371) versus non-CTO (n=4,802) lesions over a 7-year period (1997 to 2004). Characteristics of attempted lesions and factors associated with PCI outcome were evaluated. CTO lesion attempts decreased by 41% over time, from 9.6% (1997 to 1998) to 5.7% (2004, p0.0001 for trend). More contemporary CTO lesions were longer (22.4 vs 17.0 mm, p=0.006 for trend), had thrombus less often (21.3% vs 35.4%, p=0.03 for trend), and were more often treated with stents (69.8% vs 45.4% p=0.02). The rate of successful intervention for CTO lesions decreased nonsignificantly during this time, from 79.7% to 71.4% (p=0.18). Using multivariable analysis, female gender (adjusted odds ratio 0.42, 95% confidence interval 0.20 to 0.88, p=0.02), and thrombus (adjusted odds ratio 0.31, 95% confidence interval 0.15 to 0.61, p=0.0008) were associated with higher success rates, whereas the presence of severe noncardiac disease (adjusted odds ratio 1.91, 95% confidence interval 1.05 to 3.45, p=0.03) was associated with a higher risk for PCI failure. Recruitment wave and patient age were not independently related to lesion success. In conclusion, during the PCI period of 1997 to 2004, CTO lesions were attempted less frequently and success rates did not increase, indicating a need for new operator techniques or device technologies to treat this important lesion subset by a percutaneous approach.

Information about the impact of race/ethnicity on adverse outcomes after percutaneous coronary intervention (PCI) in the modern era is limited. Using consecutive patients from the National Heart, Lung, and Blood Institute Dynamic Registry, this study investigated differences in clinical presentation, treatment strategy, and acute and long-term outcomes in 3,669 white, 446 black, 301 Hispanic, and 201 Asian patients who underwent PCI. All comparisons were made to whites. Blacks were more likely than whites to be younger, women, and to present with a higher prevalence of cardiovascular risk factors (hypertension, diabetes, and smoking). Hispanics tended to be younger, hypertensive, diabetic, and to be undergoing their first cardiovascular procedure. Asians were, on average, younger, men, and presented more often with hypertension and diabetes than whites. Although the rate of stent implantation was significantly lower in blacks compared with whites (63% vs 74%, p0.001), angiographic and procedural success rates were high (or =95%) and did not differ by race/ethnicity. In-hospital mortality (0.2% vs 1.7%, p0.05) and death/myocardial infarction (MI)/coronary artery bypass grafting (CABG) (3.1% vs 5.5%, p0.05) were lower in blacks. All other in-hospital complications were similar to whites. At 1 year, there were no statistical differences in cumulative adverse event rates by ethnicity; however by 2 years there was a modestly higher mortality rate (adjusted RR 1.87; 95% confidence interval 1.15 to 3.04) and adverse event rate (death/MI, death/MI/CABG) among black patients. Thus, although differences in patient demographics, clinical presentation, angiographic characteristics and treatment strategies did not impact the incidence of acute and 1-year adverse outcomes of non-whites, there appears to be a significant reduction in event-free survival among blacks by 2 years.

A recognized complication of vagal nerve stimulation is new or worsening sleep apnea. Its pathophysiology is not clearly understood. We report a patient with obstructive sleep apnea that was directly associated with vagal nerve stimulation causing recurring vocal cord adduction. Adjusting the stimulator settings resolved the problem.

Aims An increasing number of patients undergoing percutaneous coronary intervention (PCI) have experienced previous revascularization procedures. Their outcome after PCI has seldom been compared to that of patients without prior procedures. This study investigates which elements of prior revascularization affect in-hospital and long-term outcome after PCI. Methods and Results Baseline characteristics as well as in-hospital and 1-year outcomes were compared in 4010 consecutive patients undergoing PCI in the NHLBI Dynamic Registry, categorized by type of prior procedure. In-hospital mortality was lowest and procedural success highest among patients with prior PCI only. Patients with prior coronary artery bypass grafting (CABG) had higher rates for the combined endpoint of death and myocardial infarction (MI) at 1 year compared to patients with no prior procedures. However, in multivariate regression analysis adjusting for potential confounders, neither prior PCI nor prior CABG were independent predictors of death or death/MI at 1 year. Patients with prior procedure had higher rates for repeat PCI and patients with prior PCI had higher rates for CABG during the year following the index procedures. These associations persisted after adjustment for potential confounders. Finally, patients with prior procedures had a higher prevalence of angina at 1 year. Conclusions Due to adverse baseline characteristics, patients with prior CABG have higher rates for death/MI during the first year after PCI and both groups of patients with prior procedures have higher revascularization rates. However, only the associations with repeat revascularization persist after adjustment for baseline and procedural factors.

OBJECTIVES We sought to compare survival after coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in high-risk anatomic subsets. BACKGROUND Compared with medical therapy, CABG decreases mortality in patients with three-vessel disease and two-vessel disease involving the proximal left anterior descending artery (LAD), particularly if left ventricular (LV) dysfunction is present. How survival after PTCA and CABG compares in these high-risk anatomic subsets is unknown. METHODS In the Bypass Angioplasty Revascularization Investigation (BARI), 1,829 patients with multivessel disease were randomized to an initial strategy of PTCA or CABG between 1988 and 1991. Stents and IIb/IIIa inhibitors were not utilized. Since patients in BARI with diabetes mellitus had greater survival with CABG, separate analyses of patients without diabetes were performed. RESULTS Seven-year survival among patients with three-vessel disease undergoing PTCA and CABG (n = 754) was 79% versus 84% (p = 0.06), respectively, and 85% versus 87% (p = 0.36) when only non-diabetics (n = 592) were analyzed. In patients with three-vessel disease and reduced LV function (ejection fraction

The National Heart, Lung, and Blood Institute Dynamic Registry includes 15 clinical sites in wave 1, and 16 sites in wave 2 as well as a data-coordinating center. The first wave of enrollment began in July 1997 and was completed in February 1998. The second wave began in February 1999 and ended in June 1999. There were a total of 2,526 patients in wave 1 and 2,109 patients in wave 2. Comprehensive pre-, intra-, and postprocedure (in-hospital) data were analyzed for changes between recruitment waves. Patients in wave 2 were more frequently nonwhite (por = 0.001), hypertensive by history (por = 0.001), had more significant noncardiac comorbidity (por = 0.01), and had more frequently undergone prior percutaneous coronary intervention (p0.05). Patients in wave 2 underwent percutaneous coronary intervention in a setting of acute coronary syndromes more frequently than wave 1 patients (por = 0.001). However, most interventions in both waves were performed on 1 vessel, irrespective of the extent of disease. Attempted lesions in wave 2 were longer (por = 0.001), less frequently totally occluded (por = 0.001), and more frequently in vessels with a prior stent (por = 0.01). Using the American Heart Association/American College of Cardiology lesion classification scheme, attempted lesions in wave 2 were less complex than those in wave 1 (por = 0.001). Stent use increased significantly from wave 1 (67%) to wave 2 (79%, por = 0.001) as did the use of platelet glycoprotein IIb/IIIa antagonists (wave 1, 24%; wave 2, 32%: p0.001). Procedural outcomes (angiographic success without major in-hospital adverse events) were excellent in both waves 1 (94.6%) and 2 (95.6%) and were not significantly different. However, the frequency of significant procedural coronary dissection and in- and out-of-laboratory abrupt closure were significantly less in wave 2 (por = 0.001) Discharge medications were more likely to include angiotensin-converting enzyme inhibitors, beta-adrenergic blocking agents, and hypolipidemic treatment in wave 2 than in wave 1 (por = 0.001). These data indicate a continuing aggressive approach to patient care over the time interval analyzed. Although overall procedural outcomes are excellent, procedural safety has been further enhanced. There is also a growing awareness of the importance of secondary prevention among interventional cardiologists.

Prior studies suggest that younger women are at higher risk for major adverse events following PCI; however, little is known about the association between race and adverse outcomes in this population. We evaluated 3797 women undergoing PCI in the NHLBI Dynamic Registry and compared 1 year outcomes

Objectives This study sought to evaluate the safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. Background Randomized trials have demonstrated that DES reduce the risk of target vessel revascularization (TVR) compared to BMS. This benefit is less pronounced as artery diameter increases. Whether DES are superior to BMS for larger coronary arteries in the setting of routine clinical practice is unknown. Methods We analyzed data from 869 patients undergoing de novo lesion PCI with reference vessel diameter greater than or equal to 3.5 mm in the NHLBI Dynamic Registry according to whether they were treated with DES or BMS. Patients were followed for 3 years for the occurrence of cardiovascular events. Results At 3-year follow-up, rates of TVR at 3 years were similar and low in both groups (4.4% vs. 3.7%, P = 0.62). After adjustment for differences in baseline characteristics, the adjusted hazard ratio for 3-year MI for DES was 1.85 (95% CI 0.93–3.7, P = 0.08), for TVR at 3 years 1.14 (95% CI 0.52–2.49, P = 0.75) and for mortality 0.89 (95%CI 0.49–1.62, P = 0.71). Conclusions In our study of the unrestricted use of DES for patients with lesions in larger diameter coronary arteries, first generation DES did not reduce 3-year risk of TVR. Our findings do not support the preferred use of DES over BMS for patients with lesions located in arteries >3.5 mm. It is unknown whether secondary generation DES can offer better outcome compared to BMS in large coronary vessels. Further study on this issue is warranted. © 2013 Wiley Periodicals, Inc.

Drug eluting stent (DES) failure including restenosis and stent thrombosis, or disease progression may result in target vessel revascularization (TVR) but the relative contribution of these mechanisms in the DES era is not well described. We sought to examine the predictors and presentations of patients with clinically driven TVR after DES.Patients with all lesions treated with a DES in the Dynamic Registry from 2004 to 2006 were analyzed. Included were 2691 patients with 3401 lesions. Patients with and without incident clinically driven TVR at 2years were compared according to baseline clinical, procedural, and angiographic characteristics and independent predictors of TVR and target lesion revascularization (TLR) were determined by multivariate analysis.By 2-years, TVR occurred in 7.2% of patients and TLR in 3.8%, with 71.6% and 82.5% of repeat revascularization events occurring in the first year, respectively. The indication for first TVR was myocardial infarction in 18.6% (n=34), unstable angina in 42.6% (n=78), stable coronary disease in 25.7% (n=47) and other/unknown in 13.1% (n=24). Disease progression was responsible for 47% of TVR. Among patients with TLR, restenosis was the mechanism in 86.6% and stent thrombosis in 13.4%. Independent predictors of TVR included younger age, diabetes, attempted graft lesion, lesion length30mm and prior lesion intervention. Independent predictors of TVR and TLR were similar.The incidence of clinically driven TVR is low in patients treated with DES and nearly half is attributable to disease progression, which along with the low rate of in-stent restenosis explains why the mode of presentation is often an acute coronary syndrome.

We compared the effectiveness of drug-eluting stents (DESs) to bare-metal stents (BMSs) in ostial lesions from an unrestricted patient cohort with 3-year follow-up. DESs have proved more effective at decreasing repeat revascularization rates compared to BMSs in patients with uncomplicated coronary artery disease. Whether DESs provide similar benefits in ostial lesions is not clearly defined. We analyzed data from 775 patients in the National, Heart, Lung, and Blood Institute Dynamic Registry undergoing stenting of ostial lesions with DESs or BMSs. Patients were followed for 3 years for the occurrence of myocardial infarction (MI), repeat revascularization (coronary bypass surgery/repeat percutaneous coronary intervention), and death. In total 439 patients had 464 ostial lesions treated with BMSs and 336 patients had 351 ostial lesions treated with DESs. Adjusted DES versus BMS 3-year hazard ratios were 1.03 (95% confidence interval 0.60 to 1.78, p = 0.90) for death, 1.40 (0.83 to 2.37, p = 0.21) for MI, and 0.81 (0.59 to 1.11, p = 0.19) for repeat revascularization. In patients undergoing percutaneous coronary intervention for aorto-ostial disease (n = 200), death and repeat revascularization did not differ between stent types, but DES-treated patients had more MI during follow-up. For coronary ostial disease (n = 574), 3-year observed rates of death or MI did not differ; however, repeat revascularization was more common in the BMS group. In conclusion, use of DESs for ostial lesions was associated with no difference in the hazard of death, MI, or overall rates of repeat revascularization compared to BMS use.

Percutaneous coronary intervention (PCI) for protected left main coronary artery (PLM) disease is complex because of patient and lesion factors; however, limited data exist on the outcomes of drug-eluting stent (DES) use for this indication. DEScover is a prospective observational study that enrolled consecutive patients with PCI in 2005. In-hospital and 1-year statuses were analyzed for 6,172 patients treated with DES according to LM and coronary artery bypass grafting (CABG) statuses (PLM, n = 93; previous CABG native vessel non-LM, n = 722; no previous CABG, n = 5,357). Cumulative event rates were calculated by the Kaplan–Meier method. Cox proportional hazards regression was used for multivariable analysis of adverse events. Baseline clinical, angiographic, and procedural variables differed significantly among groups, with patients with previous CABG, PLM, and non-LM having higher risk characteristics. In patients with previous CABG, after adjustment with CABG non-LM as a reference group, there were no significant differences in 1-year risk of any adverse event except a trend toward a greater risk of myocardial infarction (MI) in patients with PLM (adjusted hazard ratio 2.4, confidence interval 0.95 to 6.2, p = 0.06). However, patients after CABG (PLM and non-LM) compared to patients without previous CABG had a similar adjusted risk of death, MI, and stent thrombosis; an increased risk of target lesion revascularization (adjusted hazard ratio 1.79, confidence interval 1.2 to 2.6, p = 0.003), target vessel revascularization and death/MI/target vessel revascularization; and a lower risk of CABG (adjusted hazard ratio 0.25, confidence interval 0.09 to 0.67, p = 0.006). In conclusion, status after CABG rather than PLM location increases the risk of repeat revascularization with PCI in DES-treated patients.

Background The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP) near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD) related phenotypes. Methods and Results Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI) in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD) was significantly higher in older men (≥65 years) who were either homozygous or carriers of the obesity/lipid risk allele ("C") compared to non-carriers (odds ratio 3.4, p = 0.013) using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65) women (odds ratio 3.4, p = 0.013). The INSIG2 SNP was not associated with BMI, nor with other clinical variables. Conclusion Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.

To evaluate the efficacy and safety of drug eluting stents (DES) when compared with bare metal stents (BMS) in patients with moderate to severe calcified coronary lesions.Calcified coronary lesions present unique technical challenges during percutaneous coronary intervention (PCI) and it is not known if DES are as safe and as effective in the presence of calcium, as randomized trials typically exclude this common patient subset.We evaluated patients with PCI of a single calcified lesion enrolled across five recruitment waves in the National Heart, Lung, and Blood Institute Dynamic Registry between 1997 and 2006. Patients were divided into two groups based on the stent type- BMS and DES. The primary efficacy outcome was the need for repeat revascularization at 1 year and the primary safety outcome was a composite of death and myocardial infarction at 1 year.Among the 1,537 patients included in the analysis, 884 (57%) underwent PCI with BMS and 653 (43%) with DES. DES use was associated with a significant reduction in the risk of repeat revascularization (10.0% vs. 15.3%; P = 0.003) with no significant higher risk of primary safety outcome (9.3% vs. 10.5%; P = 0.45) when compared to the BMS group. In a propensity score adjusted analysis, DES use was associated with a significantly lower risk in repeat revascularization (HR = 0.57; 95% CI 0.40-0.82; P = 0.002) and no significant difference in the risk of death and myocardial infarction (HR = 0.78; 95% CI 0.53-1.15; P = 0.20) compared to BMS group.In this large multicenter registry of patients with a moderate to severe calcified coronary lesion, use of DES compared to BMS was associated with significant reduction in the risk of repeat revascularization without any increase in death and myocardial infarction.

Drug-eluting stents (DES) reduce the risk of restenosis, however, the benefit may not be consistent or result in fewer repeat interventions in all patient and lesion subsets. We sought to identify the clinical presentation and predictive factors of target vessel revascularization (TVR) in unselected patients treated with DES. Patients with all lesions treated with a DES in the NHLBI Dynamic Registry were analyzed. Included were 2790 patients with 3532 target lesions. All patients were followed prospectively for at least one-year. Target vessel revascularization was defined as any repeat percutaneous coronary intervention involving the target vessel. Baseline characteristics of patients with and without subsequent TVR were compared and independent predictors of TVR were determined by multivariate analysis. Clinically driven TVR occurred in 131 patients (4.7%) and 170 lesions (4.8%). The indication for first TVR was myocardial infarction (n = 29) 22.1%, unstable angina (n = 79) 60.3%, stable angina (n = 21) 16%, other (n = 2) 1.5%. Among patients with TVR the rate of stent thrombosis at 1 year was (n = 17) 13% and 15 of these patients had TVR within 3 days of ST. Several predictors of TVR were identified (Table ) the strongest being diabetes, prior in-stent restenosis, and attempted graft lesion. Stent type, sirolimus vs. other (adjusted OR 0.96, CI 0.36 –2.57) and paclitaxel vs. other (adjusted OR 0.75, CI 0.27–2.10), was not associated with TVR. Although the rate of TVR is low in patients treated with DES, certain patient and lesion subsets predict a higher risk of TVR. Of concern, unlike historical bare metal stent restenosis, TVR events were mainly related to acute coronary syndromes. These observations highlight the need for new stent technology to prevent restenosis and stent thrombosis and more aggressive medical therapy to prevent ischemic events in high risk patients. Adjusted Odds Ratio Model For Target Vessel Revascularization

BACKGROUND Recent reports suggest that off-label use of drug-eluting stents is associated with an increased incidence of adverse events. Whether the use of bare-metal stents would yield different results is unknown. METHODS We analyzed data from 6551 patients in the National Heart, Lung, and Blood Institute Dynamic Registry according to whether they were treated with drug-eluting stents or bare-metal stents and whether use was standard or off-label. Patients were followed for 1 year for the occurrence of cardiovascular events and death. Off-label use was defined as use in restenotic lesions, lesions in a bypass graft, left main coronary artery disease, or ostial, bifurcated, or totally occluded lesions, as well as use in patients with a reference-vessel diameter of less than 2.5 mm or greater than 3.75 mm or a lesion length of more than 30 mm. RESULTS Off-label use occurred in 54.7% of all patients with bare-metal stents and 48.7% of patients with drug-eluting stents. As compared with patients with bare-metal stents, patients with drug-eluting stents had a higher prevalence of diabetes, hypertension, renal disease, previous percutaneous coronary intervention and coronary-artery bypass grafting, and multivessel coronary artery disease. One year after intervention, however, there were no significant differences in the adjusted risk of death or myocardial infarction in patients with drug-eluting stents as compared with those with bare-metal stents, whereas the risk of repeat revascularization was significantly lower among patients with drug-eluting stents. CONCLUSIONS Among patients with off-label indications, the use of drug-eluting stents was not associated with an increased risk of death or myocardial infarction but was associated with a lower rate of repeat revascularization at 1 year, as compared with bare-metal stents. These findings support the use of drug-eluting stents for off-label indications.

ContextLimited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings.ObjectivesTo determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI).Design, Setting, and PatientsObservational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort.Main Outcome MeasuresFrequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up.ResultsOf 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]).ConclusionsIn contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.

It is unknown whether noncoronary vascular disease is associated with persistent cardiac risk in patients who undergo percutaneous coronary intervention (PCI). Using the National Heart, Lung, and Blood Institute Dynamic Registry, the incidence of death, myocardial infarction (MI), and repeat revascularization outcomes were compared in patients who had noncoronary vascular disease (n = 554) with patients who did not (n = 4,075). Vascular disease was defined as a history of stroke, transient ischemic attack, claudication, vascular bypass, limb amputation, or aortic aneurysm. Patients who had concomitant noncoronary vascular disease had more significant co-morbidities. Angiographic success rate was lower in patients who had concomitant noncoronary vascular disease (89.5% vs 93.2%, p0.01), whereas in-hospital adverse events, including death (2.7% vs 1.3%, p0.05), MI (4.7% vs 2.6%, p0.01), stroke (1.1% vs 0.2%, p0.001), major entry site complication (6.7% vs 3.5%, p0.001), and need for coronary artery bypass grafting (2.2% vs 1.1%, p0.05) were significantly higher. One-year death rate (10.5% vs 4.5%, p0.001) and MI rate (9.2% vs 5.2%, p0.001) were also significantly higher in patients who had vascular disease. After adjustment, vascular disease was independently associated with a higher risk of death or MI (risk ratio 1.4, 95% confidence interval 1.1 to 1.8) and death, MI, or coronary artery bypass grafting (risk ratio 1.3, 95% confidence interval 1.1 to 1.6) at 1 year. Repeat PCI rates were similar (15.9% vs 13.8%, p = NS). In conclusion, the presence of noncoronary vascular disease is an independent predictor of MI and death or MI 1 year after PCI. Because PCI is often performed before vascular surgery, these data may lend insight to the risk/benefit ratio of such an approach.

Patients with congestive heart failure (CHF) have higher rates of adverse outcomes after percutaneous coronary intervention (PCI). A comprehensive analysis of outcomes in patients with CHF in the current era has not been done. We studied the outcomes of patients with CHF who underwent PCI in the National Heart, Lung, and Blood Institute-sponsored Percutaneous Transluminal Coronary Angioplasty (PTCA) and Dynamic registries.We evaluated demographic and angiographic characteristics and the clinical outcomes of patients with CHF in the Dynamic Registry and the PTCA Registry, excluding patients with acute myocardial infarction. In the Dynamic Registry, patients with CHF (n = 503) were compared with patients without CHF (n = 4194), and patients with CHF with a preserved ejection fraction (EF) (n = 134) were compared with patients with CHF who have a reduced EF (n = 199). The patients with CHF in the 1997 through 2001 Dynamic Registry (n = 236) were then similarly compared with patients with CHF in the earlier PTCA Registry (n = 117).In the Dynamic Registry, compared with patients without CHF, patients with CHF had a higher-risk clinical and angiographic profile, and a higher mortality rate both inhospital (2.6% vs 0.4%, Por = .001) and at 1 year (13.1% vs 3.0%, P.001). Patients with reduced EF had higher inhospital mortality rates and a trend toward higher mortality at 1 year. The patients with CHF in the Dynamic Registry compared with those in the PTCA Registry had a higher risk profile yet had significantly higher procedural success rates and improved clinical outcomes.Although CHF remains a strong predictor of adverse outcomes after PCI, significant improvement seen in the past decade is likely related to improved procedural techniques and improved medical therapy.

As percutaneous coronary intervention (PCI) is most commonly performed for relief of angina, it is important to identify factors associated with recurrence of anginal symptoms.We examined symptoms at 1-year follow-up in 1755 consecutive NHLBI Dynamic Registry patients who underwent PCI in the setting of symptoms or acute infarction.At 1-year follow-up, 26% of patients reported angina in the previous 6 weeks. Younger patients and females reported more symptoms. History of coronary artery bypass graft (CABG) or PCI, prior myocardial infarction (MI), diabetes, graft disease, and extensive coronary artery disease (CAD) (4 significant lesions) were also associated with follow-up angina. Patients receiving stents reported less angina (24% vs 29%, P.05). Completely revascularized patients and those with residual single-vessel disease had comparable 1-year angina rates (23% both subgroups), while 32% of patients with residual multivessel CAD reported symptoms. Patients undergoing repeat PCI during follow-up reported more 1-year angina than others (34% vs 24%, P.001), whereas those undergoing CABG after post-PCI hospitalization had less symptoms (15% vs 26%, P.05). After adjustment for baseline symptom status and outcome of index PCI, residual CAD, and reintervention during follow-up, patient characteristics significantly predictive of angina included female sex, age62 years, and prior MI.While approximately three quarters of patients receiving PCI are angina-free at 1 year, females continue to have more symptoms, as do other subgroups including patients with history of MI or previous intervention. As these symptoms are associated with self-reported activity and quality of life limitation, evaluations of PCI should include angina as a key follow-up outcome.