Abstract Objectives The Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients ...randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echocardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die. Methods Our analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity. Results Of the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echocardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82. Conclusions The model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure.
Abstract Background Infections are the most common noncardiac complication after cardiac surgery, but their incidence across a broad range of operations, as well as the management factors that shape ...infection risk, remain unknown. Objectives This study sought to prospectively examine the frequency of post-operative infections and associated mortality, and modifiable management practices predictive of infections within 65 days from cardiac surgery. Methods This study enrolled 5,158 patients and analyzed independently adjudicated infections using a competing risk model (with death as the competing event). Results Nearly 5% of patients experienced major infections. Baseline characteristics associated with increased infection risk included chronic lung disease (hazard ratio HR: 1.66; 95% confidence interval CI: 1.21 to 2.26), heart failure (HR: 1.47; 95% CI: 1.11 to 1.95), and longer surgery (HR: 1.31; 95% CI: 1.21 to 1.41). Practices associated with reduced infection risk included prophylaxis with second-generation cephalosporins (HR: 0.70; 95% CI: 0.52 to 0.94), whereas post-operative antibiotic duration >48 h (HR: 1.92; 95% CI: 1.28 to 2.88), stress hyperglycemia (HR: 1.32; 95% CI: 1.01 to 1.73); intubation time of 24 to 48 h (HR: 1.49; 95% CI: 1.04 to 2.14); and ventilation >48 h (HR: 2.45; 95% CI: 1.66 to 3.63) were associated with increased risk. HRs for infection were similar with either <24 h or <48 h of antibiotic prophylaxis. There was a significant but differential effect of transfusion by surgery type (excluding left ventricular assist device procedures/transplant) (HR: 1.13; 95% CI: 1.07 to 1.20). Major infections substantially increased mortality (HR: 10.02; 95% CI: 6.12 to 16.39). Conclusions Major infections dramatically affect survival and readmissions. Second-generation cephalosporins were strongly associated with reduced major infection risk, but optimal duration of antibiotic prophylaxis requires further study. Given practice variations, considerable opportunities exist for improving outcomes and preventing readmissions. (Management Practices and Risk of Infection Following Cardiac Surgery; NCT01089712 )
Abstract Rationale Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures. Objectives To prospectively examine the timing, pathogens, and risk ...factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes. Methods A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model. Measurements and Main Results The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio HR, 2.83; 95% confidence interval 95% CI, 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58). Conclusions Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.
Background Cardiac contractility modulation (CCM) delivers nonexcitatory electrical signals to the heart during the absolute refractory period intended to improve contraction. Methods We tested CCM ...in 428 New York Heart Association class III or IV, narrow QRS heart failure patients with ejection fraction (EF) ≤35% randomized to optimal medical therapy (OMT) plus CCM (n = 215) versus OMT alone (n = 213). Efficacy was assessed by ventilatory anaerobic threshold (VAT), primary end point, peak V o2 (pV o2 ), and Minnesota Living with Heart Failure Questionnaire (MLWFQ) at 6 months. The primary safety end point was a test of noninferiority between groups at 12 months for the composite of all-cause mortality and hospitalizations (12.5% allowable delta). Results The groups were comparable for age (58 ± 13 vs 59 ± 12 years), EF (26% ± 7% vs 26% ± 7%), pV o2 (14.7 ± 2.9 vs 14.8 ± 3.2 mL kg−1 min−1 ), and other characteristics. While VAT did not improve at 6 months, CCM significantly improved pV o2 and MLWHFQ (by 0.65 mL kg−1 min−1 P = .024 and −9.7 points P < .0001, respectively) over OMT. Forty-eight percent of OMT and 52% of CCM patients experienced a safety end point, which satisfied the noniferiority criterion ( P = .03). Post hoc, hypothesis-generating analysis identified a subgroup (characterized by baseline EF ≥25% and New York Heart Association class III symptoms) in which all parameters were improved by CCM. Conclusions In the overall target population, CCM did not improve VAT (the primary end point) but did improve pV o2 and MLWHFQ. Cardiac contractility modulation did not have an adverse affect on hospitalizations or mortality within the prespecified boundaries. Further study is required to clarify the role of CCM as a treatment for medically refractory heart failure.
Objective The purpose of this study was to compare breastfeeding duration in mothers after delivery who were assigned randomly to a behavioral educational intervention vs enhanced usual care. Study ...Design We conducted a randomized trial. Self-identified black and Latina mothers early after delivery were assigned randomly to receive a behavioral educational intervention or enhanced usual care. The 2-step intervention aimed to prepare and educate mothers about postpartum symptoms and experiences (including tips on breastfeeding and breast/nipple pain) and to bolster social support and self-management skills. Enhanced usual care participants received a list of community resources and received a 2-week control call. Intention-to-treat analyses examined breastfeeding duration (measured in weeks) for up to 6 months of observation. This study was registered with clinicaltrial.gov ( NCT01312883 ). Results Five hundred forty mothers were assigned randomly to the intervention (n = 270) vs control subjects (n = 270). Mean age was 28 years (range, 18–46 years); 62% of the women were Latina, and 38% were black. Baseline sociodemographic, clinical, psychosocial, and breastfeeding characteristics were similar among intervention vs control subjects. Mothers in the intervention arm breastfed for a longer duration than did the control subjects (median, 12.0 vs 6.5 weeks, respectively; P = .02) Mothers in the intervention arm were less likely to quit breastfeeding over the first 6 months after delivery (hazard ratio, 0.79; 95% confidence interval, 0.65–0.97). Conclusion A behavioral educational intervention increased breastfeeding duration among low-income, self-identified black and Latina mothers during the 6-month postpartum period.
Abstract Background Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the absolute refractory period intended to improve contraction. We previously ...tested the safety and efficacy of CCM in 428 NYHA functional class III/IV heart failure patients with EF ≤35% and narrow QRS randomized to optimal medical treatment (OMT) plus CCM (n = 215) versus OMT alone (n = 213) and found no significant effect on ventilatory anaerobic threshold (VAT), the study’s primary end point. In the present analysis, we sought to identify if there was a subgroup of patients who showed a response to CCM. Methods and Results The protocol specified that multiregression analysis would be used to determine if baseline EF, NYHA functional class, pVO2 , or etiology of heart failure influenced the impact of CCM on AT. Etiology and baseline pVO2 did not affect efficacy. However, baseline NYHA functional class III and EF ≥25% were significant predictors of increased efficacy. In this subgroup (comprising 97 OMT and 109 CCM patients, ∼48% of the entire population) VAT increased by 0.10 ± 2.36 in CCM versus −0.54 ± 1.83 mL kg−1 min−1 in OMT ( P = .03) and pVO2 increased by 0.34 ± 3.11 in CCM versus −0.97 ± 2.31 ( P = .001) at 24 weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed improvement of ≥1 class in NYHA functional class ( P = .002), and 59% of CCM versus 42% of OMT subjects showed a ≥10-point reduction in Minnesota Living with Heart Failure Questionnaire ( P = .01). All of these findings were similar to those seen at 50 weeks. Conclusions The results of this retrospective hypothesis-generating analysis indicate that CCM significantly improves objective parameters of exercise tolerance in a subgroup of patients characterized by normal QRS duration, NYHA functional class III symptoms, and EF >25%.
Background Ischemic mitral regurgitation, a complication of myocardial infarction and coronary artery disease more generally, is associated with a high mortality rate and is estimated to affect 2.8 ...million Americans. With 1-year mortality rates as high as 40%, recent practice guidelines of professional societies recommend repair or replacement, but there remains a lack of conclusive evidence supporting either intervention. The choice between therapeutic options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus a better long-term correction of mitral insufficiency with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to significant variation in surgical practice. Methods and Results This article describes the design of a prospective randomized clinical trial to evaluate the safety and effectiveness of mitral valve repair and replacement in patients with severe ischemic mitral regurgitation. This trial is being conducted as part of the Cardiothoracic Surgical Trials Network. This article addresses challenges in selecting a feasible primary end point, characterizing the target population (including the degree of mitral regurgitation) and analytical challenges in this high mortality disease. Conclusions The article concludes by discussing the importance of information on functional status, survival, neurocognition, quality of life, and cardiac physiology in therapeutic decision making.
Abstract Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint ...definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assessments will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.
Randomized trials in surgery Gelijns, Annetine C., PhD; Ascheim, Deborah D., MD; Parides, Michael K., PhD ...
Surgery,
06/2009, Letnik:
145, Številka:
6
Journal Article
Background White matter hyperintensity (WMH), a common radiographic finding associated with stroke risk and outcome, has been linked to matrix metalloproteinase (MMP) activity and increased levels of ...oxidative stress in nonstroke populations. We sought to determine whether WMH severity is associated with plasma levels of MMPs and oxidative stress (F2-isoprostane) in subjects with acute ischemic stroke (AIS). Methods We measured plasma biomarker levels at baseline and 48 hours in consecutive AIS subjects. White matter hyperintensity volume (WMHv) was quantified on admission magnetic resonance imaging using a validated semiautomated protocol, and Spearman correlation coefficients were derived for all measured biomarkers. Results We enrolled 405 AIS subjects (mean age 70 ± 15 years; 58% male; median WMHv 3.4 cm3 , interquartile range 1.4-9.5). WMHv and age were strongly correlated (ρ = .57, P < .0001). WMHv and MMP-2 levels were correlated at baseline (ρ = .23, P < .0001) and at 48 hours poststroke (ρ = .19, P = .002). In multivariate analysis, 48-hour MMP-2 levels were independently associated with WMHv (β = .12, P = .04). MMP-9 and F2-isioprostane levels did not correlate with WMHv. Conclusions In AIS patients, MMP-2 levels are associated with the pre-existing burden of WMH. If validated, these findings may further elucidate the role of MMP-2 in pathophysiology of chronic cerebrovascular injury, such as WMH, and in brain susceptibility to acute ischemia.
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