Central Maine Medical Center

AIMS: Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS: Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS: The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313.

BACKGROUND: Exposure to red blood cell (RBC) transfusions has been associated with increased mortality after cardiac surgery. We examined long-term survival for cardiac surgical patients who received one or two RBC units during index hospitalization. METHODS: Nine thousand seventy-nine consecutive patients undergoing coronary artery bypass graft, valve, or coronary artery bypass graft/valve surgery at eight centers in northern New England during 2001-2004 were examined after exclusions. A probabilistic match between the regional registry and the Social Security Administration's Death Master File determined mortality through June 30, 2006. Cox Proportional Hazard and propensity methods were used to calculate adjusted hazard ratios. RESULTS: Thirty-six percent of patients (n = 3254) were exposed to one or two RBC units. Forty-three percent of RBCs were given intraoperatively, 56% in the postoperative period and 1% were preoperative. Patients transfused were more likely to be anemic, older, smaller, female and with more comorbid illness. Survival was significantly decreased for all patients exposed to 1 or 2 U of RBCs during hospitalization for cardiac surgery compared with those who received none (P < 0.001). After adjustment for patient and disease characteristics, patients exposed to 1 or 2 U of RBCs had a 16% higher long-term mortality risk (adjusted hazard ratios = 1.16, 95% CI: 1.01-1.34, P = 0.035). CONCLUSIONS: Exposure to 1 or 2 U of RBCs was associated with a 16% increased hazard of decreased survival after cardiac surgery.

BACKGROUND: Hemodilutional anemia during cardiopulmonary bypass (CPB) is associated with increased mortality during coronary artery bypass graft (CABG) surgery. The impact of intraoperative red blood cell (RBC) transfusion to treat anemia during surgery is less understood. We examined the relationship between anemia during CPB, RBC transfusion, and risk of low-output heart failure (LOF). METHODS AND RESULTS: Data were collected on 8004 isolated CABG patients in northern New England between 1996 and 2004. Patients were excluded if they experienced postoperative bleeding or received > or = 3 units of transfused RBCs. LOF was defined as need for intraoperative or postoperative intra-aortic balloon pump, return to CPB, or > or = 2 inotropes at 48 hours. Having a lower nadir HCT was also associated with an increased risk of developing LOF (adjusted odds ratio, 0.90; 95% CI, 0.82 to 0.92; P=0.016), and that risk was further increased when patients received RBC transfusion. When adjusted for nadir hematocrit, exposure to RBC transfusion was a significant, independent predictor of LOF (adjusted odds ratio, 1.27; 95% CI, 1.00 to 1.61; P=0.047). CONCLUSIONS: In this study, we observed that exposure to both hemodilutional anemia and RBC transfusion during surgery are associated with increased risk of LOF, defined as placement of an intraoperative or postoperative intra-aortic balloon pump, return to CPB after initial separation, or treatment with > or = 2 inotropes at 48 hours postoperatively, after CABG. The risk of LOF is greater among patients exposed to intraoperative RBCs versus anemia alone.

BACKGROUND: Renal insufficiency after coronary artery bypass graft (CABG) surgery is associated with increased short-term and long-term mortality. We hypothesized that preoperative patient characteristics could be used to predict the patient-specific risk of developing postoperative renal insufficiency. METHODS AND RESULTS: Data were prospectively collected on 11,301 patients in northern New England who underwent isolated CABG surgery between 2001 and 2005. Based on National Kidney Foundation definitions, moderate renal insufficiency was defined as a GFR <60 mL/min/1.73 m2 and severe renal insufficiency as a GFR <30. Patients with at least moderate renal insufficiency at baseline were eliminated from the analysis, leaving 8363 patients who became our study cohort. A prediction model was developed to identify variables that best predicted the risk of developing severe renal insufficiency using multiple logistic regression, and the predictive ability of the model quantified using a bootstrap validated C-Index (Area Under ROC) and Hosmer-Lemeshow statistic. Three percent of the patients with normal renal function before CABG surgery developed severe renal insufficiency (229/8363). In a multivariable model the preoperative patient characteristics most strongly associated with postoperative severe renal insufficiency included: age, gender, white blood cell count >12,000, prior CABG, congestive heart failure, peripheral vascular disease, diabetes, hypertension, and preoperative intraaortic balloon pump. The predictive model was significant with chi2 150.8, probability value <0.0001. The model discriminated well, ROC 0.72 (95%CI: 0.68 to 0.75). The model was well calibrated according to the Hosmer-Lemeshow test. CONCLUSIONS: We developed a robust prediction rule to assist clinicians in identifying patients with normal, or near normal, preoperative renal function who are at high risk of developing severe renal insufficiency. Physicians may be able to take steps to limit this adverse outcome and its associated increase in morbidity and mortality.

OBJECTIVE: To determine the rate of unrecognized endotracheal tube misplacement when performed by emergency medical services (EMS) personnel in a mixed urban and rural setting. METHODS: The authors conducted a prospective, observational analysis of out-of-hospital endotracheal intubations (EIs) performed by EMS personnel serving a mixed urban, suburban, and rural population. From July 1, 1998, to August 30, 1999, emergency physicians assessed and recorded the position of out-of-hospital EIs using auscultation, direct laryngoscopy, infrared CO(2) detectors, esophageal detector devices, and chest x-ray. The state EMS database also was reviewed to determine the number of EIs involving patients transported to the authors' medical center and paramedic assessment of success for these encounters. RESULTS: A total of 167 out-of-hospital EIs were recorded, of which 136 (81%) were deemed successful by EMS personnel. Observational forms were completed for 109 of the 136 patients who arrived intubated to the emergency department. Of the studied patients, 12% (13 of 109) were found to have misplaced endotracheal tubes. For the patients with unrecognized improperly placed tubes, 9% (10 of 109) were in the esophagus, 2% (2 of 109) were in the right main stem, and 1% (1 of 109) were above the cords. Paramedics serving urban and suburban areas did not perform significantly better (p < 0.05) than intermediate-level providers serving areas that are more rural. CONCLUSIONS: The incidence of unrecognized misplacement of endotracheal tubes by EMS personnel may be higher than most previous studies, making regular EMS evaluation and the out-of-hospital use of devices to confirm placement imperative. The authors were unable to show a difference in misplacement rates based on provider experience or level of training.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal.

BACKGROUND: Women are at a higher risk for bleeding/vascular complications (VC) related to cardiovascular procedures. Although the overall incidence of percutaneous coronary intervention (PCI)-related bleeding/VC has declined, the impact of this decline, specifically in women, is unknown. METHODS AND RESULTS: We studied 13 653 female and 32 334 male consecutive cases, from 2002 to 2007, in the Northern New England PCI Registry. We sought to (1) compare absolute rates of bleeding/VC in women and men over time, (2) define predictors of bleeding/VC in women and men undergoing PCI, and (3) trend the impact of female gender in predicting bleeding/VC over time. Bleeding/VC was defined as any access-site vessel injury requiring surgical intervention or bleeding requiring transfusion. The overall risk of bleeding/VC was significantly higher in women versus men (4.5+/-1.3% versus 1.6+/-0.5%; P<0.004). Over time, there was a significant (P<0.001) 50% decrease in absolute bleeding/VC rates in both women and men. After adjustment for baseline differences, female gender remained a significant predictor of increased risk in 2007 (odds ratio, 2.6; 95% CI, 1.74 to 3.91). Independent predictors of increased risk of bleeding/VC in women included older age, shock, renal failure, presentation with non-ST-elevation myocardial infraction and larger sheath sizes, whereas the use of fluoroscopy-guided access, closure devices, history of dyslipidemia or prior PCI, and use of bivalirudin were protective. CONCLUSIONS: Women undergoing PCI have had a significant decline in bleeding/VC rates during the last 6 years. Despite the improvement in procedural safety, female gender continues to be associated with a >2-fold risk of bleeding/VC compared with men.

CONTEXT: Poverty has been shown to be a determinant of health outcomes in many epidemiologic studies. OBJECTIVE: The goal of this study was to assess the association between household income and the mortality rate in cystic fibrosis (CF) patients. DESIGN, SETTING, AND PATIENTS: We selected white patients diagnosed before 18 years old and having 1 or more records in the Cystic Fibrosis Foundation Patient Registry since 1991. These 23 817 patients were linked to the 1990 US Census by their zip code of residence. The median household income was adjusted for state level differences in cost of living using the 1998 Consumer Price Index. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We examined the association between categories of the median household income and the mortality rate. We examined the association between income categories and age-related changes in pulmonary function and body weight as well as specific nutritional and pulmonary therapies. RESULTS: We found a strong monotonic association between the median household income and the mortality rate. The test of trend was significant, and this effect was maintained after adjustment for a variety of patient and disease characteristics. When the lowest income category (<20 000 dollars) is compared with the highest (> or = 50 000 dollars), the adjusted incidence rates were 90.3 and 62.6 per 10 000 person years, respectively; this represents a 44% increased risk of death in the lowest income category. Patients living in areas with lower median household income also had consistently lower pulmonary function and body weight than did those living in higher income areas. The differences in weight percentiles and forced expiratory volume in 1 second are substantial in magnitude, they appear at an early age, and they persist into adulthood for these CF patients. Prescribed nutritional treatments and screening for CF-related diabetes were significantly higher among patients living in areas with lower median household income. Prescription of deoxyribonuclease and inhaled tobramycin was not significantly associated with median household income. CONCLUSION: There was a strong association between lower household income and increased mortality rate among CF patients. Additional understanding of this effect will require more complete and direct measurement of socioeconomic status and a better understanding of treatment adherence, local environmental conditions, and especially the care of CF patients during the early years of life.

BACKGROUND: Impaired renal function after coronary artery bypass graft (CABG) surgery is a key risk factor for in-hospital mortality. However, perioperative increases in serum creatinine and the association with mortality has not been well-studied. We assessed the hypothesis that perioperative increases in creatinine are associated with increased 90-day mortality. METHODS AND RESULTS: We studied 1391 patients in northern New England undergoing CABG in 2001 and evaluated preoperative and postoperative creatinine. Patients with preoperative dialysis were excluded. Data were linked to the National Death Index to assess 90-day survival. Kaplan-Meier and log-rank techniques were used. Patients were stratified by percent increase in creatinine from baseline: <25%, 25% to 49%, 50% to 99%, > or =100%. We assessed 90-day survival and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for creatinine groups, adjusting for age and sex. Patients with the largest creatinine increases (50% to 99% or > or =100%) had significantly higher 90-day mortality compared with patients with a smaller increase (<50%; P<0.001). Adjusted HR and 95% CI confirmed patients in the higher 2 groups had an increased risk of mortality compared with the <25% (referent); however, the 25% to 49% group was not different from the referent: 1.80 (95% CI: 0.73 to 4.44), 6.57 (95% CI, 3.03 to 14.27), and 22.10 (95% CI, 11.25 to 43.39). CONCLUSIONS: Patients with large creatinine increases (> or = 50%) after CABG surgery have a higher 90-day mortality compared with patients with small increases. Efforts to identify patients with impaired renal function and to preserve renal function before cardiac surgery may yield benefits for patients in the future.

Successful mitral valve repair is dependent upon a full understanding of normal and abnormal mitral valve anatomy and function. Computational analysis is one such method that can be applied to simulate mitral valve function in order to analyse the roles of individual components and evaluate proposed surgical repair. We developed the first three-dimensional finite element computer model of the mitral valve including leaflets and chordae tendineae; however, one critical aspect that has been missing until the last few years was the evaluation of fluid flow, as coupled to the function of the mitral valve structure. We present here our latest results for normal function and specific pathological changes using a fluid-structure interaction model. Normal valve function was first assessed, followed by pathological material changes in collagen fibre volume fraction, fibre stiffness, fibre splay and isotropic stiffness. Leaflet and chordal stress and strain and papillary muscle force were determined. In addition, transmitral flow, time to leaflet closure and heart valve sound were assessed. Model predictions in the normal state agreed well with a wide range of available in vivo and in vitro data. Further, pathological material changes that preserved the anisotropy of the valve leaflets were found to preserve valve function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valve function. The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent significant advances in computational studies of the mitral valve, which allow further insight to be gained. This work is another building block in the foundation of a computational framework to aid in the refinement and development of a truly non-invasive diagnostic evaluation of the mitral valve. Ultimately, it represents the basis for simulation of surgical repair of pathological valves in a clinical and educational setting.

Background: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. Methods: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. Results: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76–996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510–1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR ( P &lt;0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients ( P =0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P &lt;0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P =0.02). The rates of Mitral Valve Academic Research Consortium–defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P =0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74–12.56; P =0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88–21.53; P &lt;0.001) were both independently associated with repeat mitral valve replacement. Conclusions: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

BACKGROUND: Increasing numbers of the very elderly are undergoing aortic valve procedures. We describe the short- and long-term survivorship for this cohort. METHODS AND RESULTS: We conducted a cohort study of 7584 consecutive patients undergoing open aortic valve surgery without (51.1%; AVR) or with (48.9%; AVR + CABG) concomitant coronary artery bypass graft surgery between November 10, 1987 through June 30, 2006. Patient records were linked to the Social Security Administration's Death Master File. Survivorship was stratified by age and concomitant CABG surgery. During 39 835 person-years of follow-up, there were 2877 deaths. Among AVR, there were 3304 patients <80 years of age, 419 patients 80 to 84 years, and 156 patients > or =85 years (24 patients >90 years). Among AVR+CABG patients, there were 2890 patients <80 years of age, 577 patients 80 to 84 years, and 238 patients > or =85 years (22 patients >90 years). Median survivorship for patients undergoing isolated AVR was 11.5 years (<80 years), 6.8 years (80 to 84 years), 6.2 years (> or =85 years); for patients undergoing AVR+CABG, median survivorship was 9.4 years (<80 years), 6.8 years (80 to 84 years), and 7.1 years (> or =85 years). Among both procedures, adjusted survivorship was significantly different across strata of age (P<0.001). These findings are similar to life expectancy of the general population from actuarial tables: 80 to 84 years (7 years) and > or =85 years (5 years). CONCLUSIONS: Survivorship among octogenarians is favorable, with more than half the patients surviving more than 6 years after their surgery. Concomitant CABG surgery does not diminish median survivorship among patients >80 years of age.

Comparison of patient mortality rates in cystic fibrosis (CF) obtained from different institutions requires the use of case-mix adjustment methods to account for baseline differences in patient and disease characteristics. There is no current professional consensus on the use of case-mix adjustment methods for use in comparing mortality rates in CF. Characteristics used for this case-mix adjustment should include those that are different across institutions and are associated with patient survival. They should not include characteristics of disease severity that may be a consequence of effectiveness of treatment. The goal of these analyses was to identify a set of these characteristics of patients or disease that would be useful for case-mix adjustment of CF mortality rates. Data from the Cystic Fibrosis Foundation Patient Registry and from the United States Census of the Population (1990) were used in these analyses. Kaplan-Meier techniques, the log-rank test, and Cox proportional hazards regression were used to estimate survivorship, calculate hazard ratios (HR), 95% confidence intervals (CI(95%)), and to conduct tests of statistical significance. The data set included all 30,469 CF patients seen at CF Care Centers from 1982-1998. There were 5,906 deaths during 508,721 person-years of follow-up. In multivariate analyses, female gender (HR 1.30, CI(95%) (1.16, 1,47), P < 0.001), nonwhite race (HR 1.48, CI(95%) (1.07, 2.04), P = 0.018), Hispanic ethnicity (HR 1.85, CI(95%) (1.42, 2.43), P < 0.001), and symptomatic presentation (respiratory, gastrointestinal, respiratory and gastrointestinal, meconium ileus, and other symptomatic presentations; HRs 1.38-1.83; P values, 0.028 to < 0.001) were associated with higher risk of death. The homozygous Delta F508 genotype (HR 1.36, CI(95%) (1.19, 1.55), P < 0.001) and neither mutation being Delta F508 (HR 1.40, CI(95%) (1.15, 1.71), P = 0.001) were also associated with higher risk of death. Patients diagnosed after 36 months of age had almost 50% reduction in risk of death compared to those diagnosed before 6 months of age (HR 0.52 CI(95%) (0.44, 0.61), P < 0.001). When patients living in zip codes with a median household income > $50,000/year (corrected for the 1999 consumer price index) were compared with those living in areas with a median household income < $20,000/year, it was apparent that those in the wealthier areas had a 40% reduced risk of death (HR 0.60, CI(95%) (0.44, 0.82), P = 0.001). All of these characteristics were independently significant predictors of death, and all of these characteristics differed significantly across the CF Care Centers. This case-mix adjustment model uses patient and disease characteristics available at the time of diagnosis of CF, and is not believed to be influenced by subsequent treatment to predict the risk of death. If these case-mix adjustment methods are adopted broadly, they will make it possible to study treatment effects and differences in mortality outcomes, while adjusting for baseline differences in patient and disease characteristics.

Objective: To determine the rate of unrecognized endotracheal tube misplacement when performed by emergency medical services (EMS) personnel in a mixed urban and rural setting. Methods: The authors conducted a prospective, observational analysis of out-of-hospital endotracheal intubations (EIs) performed by EMS personnel serving a mixed urban, suburban, and rural population. From July 1, 1998, to August 30, 1999, emergency physicians assessed and recorded the position of out-of-hospital EIs using auscultation, direct laryngoscopy, infrared CO 2 detectors, esophageal detector devices, and chest x-ray. The state EMS database also was reviewed to determine the number of EIs involving patients transported to the authors' medical center and paramedic assessment of success for these encounters. Results: A total of 167 out-of-hospital EIs were recorded, of which 136 (81%) were deemed successful by EMS personnel. Observational forms were completed for 109 of the 136 patients who arrived intubated to the emergency department. Of the studied patients, 12% (13 of 109) were found to have misplaced endotracheal tubes. For the patients with unrecognized improperly placed tubes, 9% (10 of 109) were in the esophagus, 2% (2 of 109) were in the right main stem, and 1% (1 of 109) were above the cords. Paramedics serving urban and suburban areas did not perform significantly better (p < 0.05) than intermediate-level providers serving areas that are more rural. Conclusions: The incidence of unrecognized misplacement of endotracheal tubes by EMS personnel may be higher than most previous studies, making regular EMS evaluation and the out-of-hospital use of devices to confirm placement imperative. The authors were unable to show a difference in misplacement rates based on provider experience or level of training.

BACKGROUND: Use of endoscopic saphenous vein harvesting has developed into a routine surgical approach at many cardiothoracic surgical centers. The association between this technique and long-term morbidity and mortality has recently been called into question. The present report describes the use of open versus endoscopic vein harvesting and risk of mortality and repeat revascularization in northern New England during a time period (2001 to 2004) in which both techniques were being performed. METHODS AND RESULTS: From 2001 to 2004, 8542 patients underwent isolated coronary artery bypass grafting procedures, 52.5% with endoscopic vein harvesting. Surgical discretion dictated the vein harvest approach. The main outcomes were death and repeat revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 4 years of the index admission. The use of endoscopic vein harvesting increased from 34% in 2001 to 75% in 2004. In general, patients undergoing endoscopic vein harvesting had greater disease burden. Endoscopic vein harvesting was associated with an increased adjusted risk of bleeding requiring a return to the operating room (2.4 versus 1.7; P=0.03) but a decreased risk of leg wound infections (0.2 versus 1.1; P<0.001). Use of endoscopic vein harvesting was associated with a significant reduction in long-term mortality (adjusted hazard ratio, 0.74; 95% confidence interval, 0.60 to 0.92) but a nonsignificant increased risk of repeat revascularization (adjusted hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74). Similar results were obtained in propensity-stratified analysis. CONCLUSIONS: During 2001 to 2004 in northern New England, the use of endoscopic vein harvesting was not associated with harm. There was a nonsignificant increase in repeat revascularization, and survival was not decreased.

This article describes a bilingual mindfulness meditation-based stress reduction program in an inner-city setting. Mindfulness meditation is defined, and the practices of breathing meditation, eating meditation, walking meditation, and mindful yoga are described. Data analysis examined compliance, medical and psychologic symptom reduction, and changes in self-esteem, of English- and Spanish-speaking patients who completed the 8-week Stress Reduction and Relaxation Program at the Community Health Center in Meriden, Conn. Statistically significant decreases in medical and psychologic symptoms and improvement in self-esteem were found. Many program completers reported dramatic changes in attitudes, beliefs, habits, and behaviors. Despite the limitations of the research design, these findings suggest that a mindfulness meditation course can be an effective health care intervention when utilized by English- and Spanish-speaking patients in an inner-city community health center. The article includes a discussion of factors to be considered when establishing a mindfulness meditation-based stress reduction program in a health care setting.

PURPOSE: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy. DESIGN: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator. PARTICIPANTS: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53). METHODS: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks. MAIN OUTCOME MEASURES: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups. CONCLUSIONS: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.

The remodeling that occurs after a posterolateral myocardial infarction can alter mitral valve function by creating conformational abnormalities in the mitral annulus and in the posteromedial papillary muscle, leading to mitral regurgitation (MR). It is generally assumed that this remodeling is caused by a volume load and is mediated by an increase in diastolic wall stress. Thus, mitral regurgitation can be both the cause and effect of an abnormal cardiac stress environment. Computational modeling of ischemic MR and its surgical correction is attractive because it enables an examination of whether a given intervention addresses the correction of regurgitation (fluid-flow) at the cost of abnormal tissue stress. This is significant because the negative effects of an increased wall stress due to the intervention will only be evident over time. However, a meaningful fluid-structure interaction model of the left heart is not trivial; it requires a careful characterization of the in-vivo cardiac geometry, tissue parameterization though inverse analysis, a robust coupled solver that handles collapsing Lagrangian interfaces, automatic grid-generation algorithms that are capable of accurately discretizing the cardiac geometry, innovations in image analysis, competent and efficient constitutive models and an understanding of the spatial organization of tissue microstructure. In this manuscript, we profile our work toward a comprehensive fluid-structure interaction model of the left heart by reviewing our early work, presenting our current work and laying out our future work in four broad categories: data collection, geometry, fluid-structure interaction and validation.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection.

PURPOSE: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye. DESIGN: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study. METHODS: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo) and dosed twice daily (BID) for 28 days. Key eligibility criteria included exacerbation in corneal staining and ocular discomfort in the Controlled Adverse Environment (CAE(SM)) on two visits, separated by 1 week of BID dosing with artificial tears. Safety and efficacy were evaluated at baseline, throughout treatment, and for 2 weeks post-treatment. The pre-specified primary outcome measures were fluorescein corneal staining post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes included the pre-, post-, and the change from pre- to post-CAE fluorescein and lissamine green staining in both corneal and conjunctival regions, as well as individual diary symptoms. RESULTS: The prespecified primary endpoints were not met. Compared with placebo, fluorescein corneal staining at day 28 was significantly improved (P < 0.05) in the 1% MIM-D3 group for the assessment of change from pre-CAE to post-CAE. In addition, following CAE exposure, patients in the 1% MIM-D3 group showed significant improvements versus placebo (P < 0.05) in inferior fluorescein and lissamine green staining after 14 and 28 days. Compared with placebo, patients in the 5% MIM-D3 group reported significantly lower daily diary scores for ocular dryness (P < 0.05). In a subgroup defined by higher symptom scores during the run-in period, significant treatment effects (P < 0.05) were observed for diary symptoms for both MIM-D3 doses. Ocular adverse events were mild and not considered to be treatment-related. CONCLUSION: Treatment with topical ophthalmic MIM-D3 demonstrated protection against the effects of a CAE challenge on dry eye signs, reduced patient-reported diary symptoms, with a favorable safety profile.