Closing the gap: cardiovascular disease in women.

Cardiovascular disease (CVD) in women remains understudied, under-recognized, underdiagnosed and undertreated. Initiatives such as the Lancet Women and Cardiovascular Disease Commission help to identify sex and gender-related gaps in research, care and outcomes and to guide next steps in addressing them. This article highlights important aspects of the Lancet Commission report and expands on the evidence and proposed strategies for reducing the global burden of CVD in women. Furthermore, the article explores the benefits of cross-specialty collaborations for the treatment and prevention of CVD in women and discusses the impact of gender-related disparities in academic cardiology.

Primary prevention of cardiovascular disease in women.

Ischemic heart disease is the primary cause of cardiovascular disease (CVD) mortality in both men and women. Strategies targeting traditional modifiable risk factors are essential - including hypertension, smoking, dyslipidemia and diabetes mellitus - particularly for atherosclerosis, but additionally for stroke, heart failure and some arrhythmias. However, challenges related to education, screening and equitable access to effective preventative therapies persist, and are particularly problematic for women around the globe and those from lower socioeconomic groups. The association of female-specific risk factors (e.g. premature menopause, gestational hypertension, small for gestational age births) with CVD provides a potential window for targeted prevention strategies. However, further evidence for specific effective screening and interventions is urgently required. In addition to population-level factors involved in increasing the risk of suffering a CVD event, efforts are leveraging the enormous potential of blood-based 'omics', improved imaging biomarkers and increasingly complex bioinformatic analytic approaches to strive toward more personalized early disease detection and personalized preventative therapies. These novel tactics may be particularly relevant for women in whom traditional risk factors perform poorly. Here we discuss established and emerging approaches for improving risk assessment, early disease detection and effective preventative strategies to reduce the mammoth burden of CVD in women.

Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications.

Although microfluidic micro-electromechanical systems (MEMS) are well suited to investigate the effects of mechanical force on large populations of cells, their high-throughput capabilities cannot be fully leveraged without optimizing the experimental conditions of the fluid and particles flowing through them. Parameters such as flow velocity and particle size are known to affect the trajectories of particles in microfluidic systems and have been studied extensively, but the effects of temperature and buffer viscosity are not as well understood. In this paper, we explored the effects of these parameters on the timing of our own cell-impact device, the µHammer, by first tracking the velocity of polystyrene beads through the device and then visualizing the impact of these beads. Through these assays, we find that the timing of our device is sensitive to changes in the ratio of inertial forces to viscous forces that particles experience while traveling through the device. This sensitivity provides a set of parameters that can serve as a robust framework for optimizing device performance under various experimental conditions, without requiring extensive geometric redesigns. Using these tools, we were able to achieve an effective throughput over 360 beads/s with our device, demonstrating the potential of this framework to improve the consistency of microfluidic systems that rely on precise particle trajectories and timing.

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq) analysis on eight tumor specimens. Taqman-based quantitative Reverse-transcription polymerase chain reaction (qRT-PCR), western analysis and immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1) was carried out on tissue specimens. Cell viability assays of MPM cell lines were carried out to assess sensitivity to specific small molecule inhibitors. RESULTS: Bioinformatics analysis of the microarray data followed by pathway analysis revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most significantly altered in MPM tumors with upregulation of 18 component genes, including MAD2L1 gene. We validated the microarray data for MAD2L1 expression using quantitative qRT-PCR and western blot analysis on tissue lysates. Additionally, we analyzed expression of the MAD2L1 protein by IHC using an independent tissue microarray set of 80 MPM tissue samples. Robust clustering of gene expression data revealed three novel subgroups of tumors, with unique expression profiles, and showed differential expression of MSAC pathway genes. Network analysis of the microarray data showed the cytoskeleton/spindle microtubules network was the second-most significantly affected network. We also demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting the microtubules have great efficacy in decreasing viability of 14 MPM cell lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant deregulation of the MSAC pathway and the microtubule network, it can be classified into three novel molecular subgroups of potential therapeutic importance and epothilone B is a promising therapeutic agent for MPM.

Endothelial progenitor cell mobilization by preoperative exercise: a bone marrow response associated with postoperative outcome.

BACKGROUND: Preoperative anaemia is associated with increased morbidity in patients undergoing major surgery. Whether erythrocytes are the only bone-marrow-derived cell lineage that associates with increased surgical complications is unknown. This prospective observational trial studied the mobilization of endothelial progenitor cells (EPCs) in response to exercise in association with postoperative complications. METHODS: After IRB approval, 60 subjects undergoing major thoracic surgery were exercised to exhaustion (peak V̇(O2)). Peripheral blood collected before and after peak exercise was quantified for EPC lineages by fluorescence-activated cell sorter analysis. Complication analysis was based on the Clavien-Dindo classification. RESULTS: Exhaustive exercise increased EPC [CD45-133+34+ cells=150 (0.00-5230) to 220 (0.00-1270) cells µl(-1); median change (range)=20 (-4,180-860) cells µl(-1); P=0.03] but not mature endothelial cell (EC) subpopulations. Pre-exercise levels [odds ratio (OR)=0.86, 95% confidence interval (CI): 0.37-2.00, P=0.72), change after exercise as a continuous variable (OR=0.95, 95% CI: 0.41-2.22, P=0.91) and a positive response after exercise (change >0 cells µl(-1); OR=0.41, 95% CI: 0.13-1.28, P=0.12) were not statistically significantly associated with the incidence of postoperative complications. Post-hoc receiver operating characteristic curve analyses revealed that subjects with a CD45-133+34+ increase ≥60 cells µl(-1) in response to exercise suffered fewer postoperative complications [86% sensitivity, 48% specificity and AUC=0.67 (95% CI: 0.52-0.81)]. CONCLUSIONS: Preoperative exercise induces EPC into the peripheral circulation. Subjects with a poor EPC response had a pre-existing propensity for postoperative complications. This warrants further research into the role of bone marrow function as a critical component to endothelial repair mechanisms. CLINICAL TRIAL REGISTRATION: IRB 2003-0434 (University of Texas M.D. Anderson Cancer Center, Houston, TX, USA).

Concordance of studies for nodal staging is prognostic for worse survival in esophageal cancer.

Pretreatment clinical staging in esophageal cancer influences prognosis and treatment strategy. Current staging strategies utilize multiple imaging modalities, and often the results are contradictory. No studies have examined the implications of concordance of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) when used for the evaluation of nodal disease. The objective of this study was to determine if concordance of CT, PET, or EUS for nodal disease predicts worse overall survival. We reviewed 615 esophageal cancer patients with pretreatment CT, PET, and EUS that underwent esophagectomy for survival outcomes based on concordance of studies for nodal disease. Concordant N+ is defined as two or three studies positive for nodal disease; non-concordant N+ is defined as only one positive study. Node-positive disease by any study predicted shorter survival than node-negative disease (42% vs. 73% 5-year survival; P<0.001). Additionally, non-concordant N+ patients had shorter survival than N- patients (52% vs. 73% 5-year survival; P<0.001). Concordant N+ patients had shorter survival than non-concordant N+ patients (38- vs. 61-month median survival; P=0.017). There were no statistically significant differences in survival based on specific combinations of studies. When PET was disregarded, patients with both CT+ and EUS+ had shorter survival than patients with either CT+ or EUS+ (39- vs. 58-month median survival; P=0.029). Pretreatment CT, PET, or EUS concordance for node-positive disease predicts shorter overall survival in patients that undergo esophagectomy for esophageal cancer. Predicting survival in esophageal cancer should consider the synergistic capabilities of CT, PET, and EUS in evaluating nodal status.

Aggregation kinetics of SERS-active nanoparticles in thermally stirred sessile droplets.

The aggregation kinetics of silver nanoparticles in sessile droplets were investigated both experimentally and through numerical simulations as a function of temperature gradient and evaporation rate, in order to determine the hydrodynamic and aggregation parameters that lead to optimal surface-enhanced Raman spectroscopic (SERS) detection. Thermal gradients promote effective stirring within the droplet. The aggregation reaction ceases when the solvent evaporates forming a circular stain consisting of a high concentration of silver nanoparticle aggregates, which can be interrogated by SERS leading to analyte detection and identification. We introduce the aggregation parameter, Γa ≡ τ(evap)/τ(a), which is the ratio of the evaporation to the aggregation time scales. For a well-stirred droplet, the optimal condition for SERS detection was found to be Γ(a,opt) = kc(NP)τ(evap) ≈ 0.3, which is a product of the dimerization rate constant (k), the concentration of nanoparticles (cNP), and the droplet evaporation time (τ(evap)). Near maximal signal (over 50% of maximum value) is observed over a wide range of aggregation parameters 0.05 < Γa < 1.25, which also defines the time window during which trace analytes can be easily measured. The results of the simulation were in very good agreement with experimentally acquired SERS spectra using gas-phase 1,4-benzenedithiol as a model analyte.

Drug-eluting balloons for side branch stenting during bifurcation percutaneous coronary intervention.

Drug-eluting balloons (DEB) were developed to address in-stent restenosis among other indications but have also recently been shown safe and efficacious in the context of bifurcation. By eliminating both the stent and the polymer, stent thrombosis can be avoided, while still delivering an antiproliferative agent to reduce the risk of restenosis. Bifurcation lesions account for approximately 15% to 20% of all percutaneous coronary interventions and reflect a higher risk of in-stent restenosis. Complex 2-stent techniques have been shown to increase the periprocedural myocardial infarction and stent thrombosis, while side branch restenosis rates remain a drawback for even provisional stenting. In-stent restenosis of complex bifurcation lesions can increase the complexity of the intervention strategy at a rate of about 14%, often caused by DES restenosis. Drug-eluting balloons have been shown to be a good interventional option in several randomized clinical trials to prevent and treat coronary in-stent restenosis as well as in nonrandomized series in the treatment of de novo lesions in small coronary vessels and bifurcation lesions. The next generation of DEB are being designed with improved coating platforms to provide more precise drug delivery to the tissue, which will enhance their efficacy.

Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.

Patients with high body mass index tend to have lower stage of esophageal carcinoma at diagnosis.

High body mass index (H-BMI; ≥25 kg/m(2) ) is common in US adults. In a small cohort of esophageal cancer (EC) patients treated with surgery, H-BMI and diagnosis of early stage EC appeared associated. We evaluated a much larger cohort of EC patients. From a prospectively maintained database, we analyzed 925 EC patients who had surgery with or without adjunctive therapy. Various statistical methods were used. Among 925 patients, 69% had H-BMI, and 31% had normal body mass index (<25 kg/m(2) ; N-BMI). H-BMI was associated with men (P<0.001), Caucasians (P=0.064; trend), lower esophageal localization (P<0.001), adenocarcinoma histology (P<0.001), low baseline cT-stage (P=0.003), low baseline overall clinical stage (P=0.003), coronary artery disease (P=0.036), and diabetes (P<0.001). N-BMI was associated with weight loss (P<0.001), alcohol abuse (P=0.056; trend), ever/current smoking (P=0.014), and baseline cN+ (P=0.018). H-BMI patients with cT1 tumors (n=110) had significantly higher rates of gastresophageal reflux disease symptoms (P<0.001), gastresophageal reflux disease history (P<0.001), and Barrett's esophagus history (P<0.001) compared with H-BMI patients with cT2 tumors (n=114). Median survival of N-BMI patients was 36.66 months compared with 53.20 months for H-BMI patients (P=0.005). In multivariate analysis, older age (P<0.001), squamous histology (P=0.002), smoking (P=0.040), weight loss (P=0.002), high baseline stage (P<0.001), high number of ypN+ (P=0.005), high surgical stage (P<0.001), and American Society of Anesthesia scores, three out of four (P<0.001) were independent prognosticators for poor overall survival. We were able to perform propensity-based analysis of surgical complications between H-BMI and N-BMI patients. A comparison of fully matched 376 patients (188 with H-BMI and 188 with N-BMI) found no significant differences in the rate of complications between the two groups. This larger data set confirms that a fraction of H-BMI patients with antecedent history is diagnosed with early baseline EC. Upon validation of our data in an independent cohort, refinements in surveillance of symptomatic H-BMI patients are warranted and could be implemented. Our data also suggest that H-BMI patients do not experience higher rate of surgical complications compared with N-BMI patients.

Minimally invasive esophagectomy versus open esophagectomy, a symptom assessment study.

Minimally invasive esophagectomy (MIE) is used with hope to decrease the morbidity associated with an open esophagectomy. Reflux and dumping syndromes are the most important functional complaints in patients after esophagectomy. This study compares the functional benefits of MIE with open esophagectomy. The study enrolled patients who underwent either minimally invasive or open esophagectomy for cancer between 2004 and 2009. No patients in the MIE group had a pyloroplasty or myotomy. Each patient in the MIE group was paired to a patient in the open esophagectomy group via propensity matching. Matching variables included age, race, gender, preoperative treatment, history of prior cancer, American Society of Anesthesiologists Risk Scale, performance status, clinical stage, body mass index, histology, level of anastomosis, and time elapsed since surgery. The patients were asked to answer 26 questions about their reflux and dumping using validated questionnaires. A total of 181 patients were included in the study. From this group, 44 pairs of patients were created and used for the analysis. The median follow-up was 12.1 months for the MIE group and 18.3 months for the open group. The reflux score was slightly worse in the MIE group (5.5 versus 3.5, P= 0.021). There was no difference in the dumping symptoms between the two groups. The most common complaints seen in the dumping questionnaire in almost one-third of all patients were early satiety, abdominal discomfort, nausea, and diarrhea. Of the patients, 77% were satisfied or very satisfied with their condition in the MIE group compared with 93% in the open group (P= 0.287). Reflux, dumping, and overall satisfaction after MIE without pyloroplasty are comparable with those obtained after open esophagectomy with a pyloric drainage procedure.

Future stent drug delivery systems.

Drug-eluting stents (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced in-stent restenosis and repeat revascularization compared with bare metal stent (BMS) across nearly all lesion and patient subsets. However, the small number of patients with in-stent restenosis after DES treatment still exists. Furthermore, concerns about long-term safety of DES are raised, particularly regarding the higher-than-expected late-event thrombosis. There is no doubt that the DES will continue to play a pivotal role in the treatment of coronary artery disease, yet future designs need to incorporate features that reduce thrombosis and promote endothelialization along with maintaining the efficacy. This review focuses on novel generation of DES, discussing new programs, including new antiproliferative agents, novel polymeric and non polymeric stents.

Revascularization of unprotected left main coronary artery disease with percutaneous coronary intervention: the role of drug-eluting stents.

The percutaneous revascularization of left main coronary artery stenosis has until recently been reserved for patients at prohibitive surgical risk or for selected emergent cases. This adopted practice of coronary artery bypass grafting, as the standard of care for left main coronary artery stenosis, has largely occurred secondary to disappointing results with bare metal stents implanted in the left main coronary artery. However, in the current era of drug-eluting stents (DES) which significantly reduce restenosis compared to bare metal stents, there has been a renewed interest in examining the role of percutaneous coronary intervention as a means of revascularization of left main disease. This article discusses recent and ongoing studies investigating the role of percutaneous intervention of left main disease, with an emphasis on the use of DES for this purpose.

Contrast-induced nephropathy: definition, epidemiology, and patients at risk.

Radiological procedures utilizing intravascular iodinated contrast media injections are being widely applied for both diagnostic and therapeutic purposes. This has resulted in an increasing incidence of procedure-related contrast-induced nephropathy (CIN). The definition of CIN includes absolute (> or = 0.5 mg/dl) or relative increase (> or = 25%) in serum creatinine at 48-72 h after exposure to a contrast agent compared to baseline serum creatinine values, when alternative explanations for renal impairment have been excluded. Although the risk of renal function impairment associated with radiological procedures is low (0.6-2.3%) in the general population, it may be very high in selected patient subsets (up to 20%), especially in patients with underlying cardiovascular disease. This review provides information on the known risk factors for the development of CIN, and completes with describing user-friendly CIN risk score based on the readily available information.

Differential impact on survival of electrocardiographic Q-wave versus enzymatic myocardial infarction after percutaneous intervention: a device-specific analysis of 7147 patients.

BACKGROUND: The relative prognostic importance of ECG myocardial infarction (MI) after intervention compared with varying degrees of enzymatic elevation has not been characterized, and the device-specific implications of periprocedural MI are also unknown. METHODS AND RESULTS: Serial creatine phosphokinase (CPK)-MB levels were determined after elective percutaneous intervention of 12 098 lesions in 7147 consecutive patients at a tertiary referral center. Procedural, in-hospital, and follow-up data were collected by independent research nurses, and clinical and ECG events were adjudicated by a separate committee. Stents were implanted in 50.6% of lesions, atheroablation was performed in 54.8%, and PTCA alone was performed in 9.8%. The peak periprocedural CPK-MB level was >3x the upper limit of normal (ULN) in 17.9% of patients, and Q-wave MI developed in 0.6%. By multivariate analysis, the periprocedural development of new Q waves was the most powerful independent determinant of death (2-year mortality rate, 38.3%; hazard ratio, 9.9; P<0.0001). Non-Q-wave MI with CPK-MB >8x ULN was also a strong predictor of death (2-year mortality rate, 16.3%; hazard ratio, 2.2; P<0.0001); survival was unaffected by lesser degrees of CPK-MB elevation. Though CPK-MB elevation was more common after atheroablation and stenting than PTCA, the rates of Q-wave MI and survival were device-independent. CONCLUSIONS: Myonecrosis after percutaneous intervention is common in a high-risk referral population dominated by atheroablation and stent use. Large periprocedural infarctions (signified by new Q waves and CPK-MB >8xULN) are powerful determinants of death, whereas lesser degrees of CPK-MB release and specific device use do not adversely affect survival.

One-year clinical outcome after minimally invasive direct coronary artery bypass.

BACKGROUND: Minimally invasive coronary artery bypass (MIDCAB) is a new surgical technique by which the left internal mammary artery is anastomosed under direct visualization to the left anterior descending artery without cardiopulmonary bypass. METHODS AND RESULTS: We followed all 274 patients who underwent MIDCAB from the time it was introduced at a single center. In-hospital and 1-year clinical events were source-documented and adjudicated. The in-hospital major acute cardiac event rate was 2.2%; this included a 1.1% mortality rate. At 1 year, the respective rates were 7.8% and 2. 5%. When compared with the initial 100 procedures, the subsequent 174 procedures had shorter vessel occlusion times (10+/-5 versus 14+/-6 minutes; P:=0.009), times to extubation (6+/-3 versus 14+/-10 hours; P:<0.001), and lengths of hospital stay (2.1+/-1.9 versus 3. 2+/-3.1 days; P:=0.04). Cumulative 1-year adverse cardiac events were 11% in the initial 100 cases and 6% in the subsequent 174 cases (P:=0.17). CONCLUSIONS: Excellent clinical results can be achieved with the MIDCAB technique. The clinical adverse event rate may decrease with accumulated experience.

Safety of intracoronary gamma-radiation on uninjured reference segments during the first 6 months after treatment of in-stent restenosis: a serial intravascular ultrasound study.

BACKGROUND: The effects of endovascular irradiation on uninjured reference segments during the treatment of in-stent restenosis are unknown. METHODS AND RESULTS: In the Washington Radiation for In-Stent restenosis Trial (WRIST), patients with in-stent restenosis were first treated with conventional catheter-based techniques and then randomized (blinded) to receive either gamma-irradiation ((192)Ir) or a placebo (dummy seeds). We identified all patients in whom the active (n=19) or dummy seeds (n=19) extended >10 mm proximal and distal to the in-stent restenosis lesion. Serial (postirradiation and follow-up) external elastic membrane (EEM), lumen, and plaque and media (EEM-lumen) areas were measured (using intravascular ultrasound) every 1 mm over 5-mm-long reference segments that were 6 to 10 mm proximal and distal to the in-stent restenosis lesion. During follow-up, a similar small increase occurred in the plaque and media area in the proximal and distal reference segments in both (192)Ir and placebo patients. However, in the (192)Ir patients, an increase in both proximal and distal EEM area occurred; as a result, no change in lumen area occurred. Conversely, in the placebo patients, the proximal reference EEM area decreased, and no change occurred in the distal reference EEM area; this contributed to a decrease in lumen area. CONCLUSIONS: There was no evidence of a deleterious effect of gamma-irradiation on angiographically normal uninjured reference segments in the first 6 months after the treatment of in-stent restenosis.