Calcium chloride in neonatal parenteral nutrition: A 15 year experience.

OBJECTIVE: The objective of this study was to determine if outcomes at our neonatal intensive care units (NICUs) since we began using calcium chloride (CaCl2) as our preferred calcium additive in order to reduce aluminum (Al) exposure are within expected outcome ranges for NICUs in the U.S. where calcium gluconate in glass vials (CaGlu-Gl) has been the preferred additive. STUDY DESIGN: A retrospective study of very low birth weight infants born between January 1, 2000 and December 31, 2014. Outcomes in two intensive care units (NICUs) using CaCl2 were compared to all U.S. NICUs in the Vermont Oxford Network. Primary outcomes were chronic lung disease (CLD), percent requiring supplemental oxygen at 28 days, and mortality excluding early deaths (MEED). The incidence of IV infiltrates of all admissions to the study NICUs in 2013-2014 was compared to the literature. RESULTS: The incidence of CLD and those requiring oxygen at 28 days were 24.0% vs 28.6% and 46.2% vs 51.8% for the study NICUs compared to all U.S. NICUs, respectively (both p < 0.0001). The MEED was 8.7% vs 10.3% (p < 0.002). All major morbidities were lower at the study NICUs. The incidence of infiltrates was lower than that in the literature. CONCLUSION: The use of CaCl2 was not associated with any detectable adverse effects. Calcium chloride appears to be a safe alternative to the use of CaGlu-Gl based upon studies of clinical outcomes.

Comparison of outcomes after aortic valve replacement with a mechanical valve or a bioprosthesis using microsimulation.

BACKGROUND: Mechanical valves and bioprostheses are widely used for aortic valve replacement. Though previous randomised studies indicate that there is no important difference in outcome after implantation with either type of valve, knowledge of outcomes after aortic valve replacement is incomplete. OBJECTIVE: To predict age and sex specific outcomes of patients after aortic valve replacement with bileaflet mechanical valves and stented porcine bioprostheses, and to provide evidence based support for the choice of prosthesis. METHODS: Meta-analysis of published results of primary aortic valve replacement with bileaflet mechanical prostheses (nine reports, 4274 patients, and 25,726 patient-years) and stented porcine bioprostheses (13 reports, 9007 patients, and 54,151 patient-years) was used to estimate the annual risks of postoperative valve related events and their outcomes. These estimates were entered into a microsimulation model, which was employed to calculate age and sex specific outcomes after aortic valve replacement. RESULTS: Life expectancy (LE) and event-free life expectancy (EFLE) for a 65 year old man after implantation with a mechanical valve or a bioprosthesis were 10.4 and 10.7 years and 7.7 and 8.4 years, respectively. The lifetime risk of at least one valve related event for a mechanical valve was 48%, and for a bioprosthesis, 44%. For LE and EFLE, the age crossover point between the two valve types was 59 and 60 years, respectively. CONCLUSIONS: Meta-analysis based microsimulation provides insight into the long term outcome after aortic valve replacement and suggests that the currently recommended age threshold for implanting a bioprosthesis could be lowered further.

Incidence of embolism and paravalvar leak after St Jude Silzone valve implantation: experience from the Cardiff Embolic Risk Factor Study.

BACKGROUND: Silver coating of the sewing ring (Silzone) was introduced as a modification of the St Jude Medical standard valve to provide antibacterial protection, but the valve has recently been withdrawn. OBJECTIVE: To study patients with these prostheses to assess possible adverse effects, and to guide their follow up. DESIGN: Prospective observational study of risk factors for stroke after valve replacement. SETTING: Cardiology and cardiac surgery departments in a tertiary centre. PATIENTS: There were 51 patients with Silzone and 116 with St Jude Medical standard valves. Patients undergoing aortic valve replacement were well matched for stroke risk factors. Silzone patients with mitral valve replacement were younger (mean (SD) age 61 (10) v 66 (7) years), more likely to be female (95% v 65%), and had more pulmonary arterial hypertension (100% v 78%), but fewer coronary artery bypass grafts (5% v 33%) than patients with standard mitral valve replacements (all p < 0.05). RESULTS: Follow up was 100% in the Silzone group (mean duration 3.0 (0.9) years) and 97.4% in the standard group (4.7 (1.4) years). Survival, morbidity, and anticoagulant control were documented over 682 follow up years (153 for Silzone and 529 for standard). There were six embolic strokes and one peripheral embolism in the Silzone group, all within three months after operation, and five embolic strokes and one peripheral embolism in the standard group. Freedom from major thromboembolism at three months was 65% in the Silzone mitral valve replacement group and 100% in the standard mitral valve replacement group (difference 35%, 95% confidence interval 8% to 62%). There was one reoperation for paravalvar leak in the standard group, but none in the Silzone group (NS). Anticoagulant control in the two groups was similar. CONCLUSIONS: Patients with Silzone mitral valves had a high rate of early postoperative embolism but no excess paravalvar leak.

Assessing the benefit of biological valve prostheses: cumulative incidence (actual) vs. Kaplan-Meier (actuarial) analysis.

OBJECTIVE: The standard method of analysing structural valve degeneration (SVD) of biological prostheses is the Kaplan-Meier method. In order to assess SVD with regard to competing risks (e.g. death particularly in elderly patients) cumulative incidence (actual analysis) was compared to Kaplan-Meier (actuarial analysis). METHODS: We retrospectively analysed 257 patients older than 60 years, who underwent mitral valve replacement with different biological prostheses between 1974 and 2000. Reoperation-free survival was determined, both according to Kaplan-Meier and cumulative incidence analysis. RESULTS: For the total group of patients older than 60 years, the 10- and 15-year freedom from reoperation was 79+/-5 and 55+/-8%, respectively, according to Kaplan-Meier and 90+/-2 and 83+/-3% according to cumulative incidence analysis. For patients older than 65 years of age (n=170), Kaplan-Meier analysis revealed 85+/-7% freedom from reoperation at 10 years vs. 94+/-3% according to cumulative incidence analysis. For those between 60 and 65 years of age (n=87), Kaplan-Meier freedom from reoperation was 76+/-7% at 10 years and 48+/-9% at 15 years vs. 86+/-4 and 75+/-5% according to cumulative incidence analysis. CONCLUSIONS: Kaplan-Meier analysis overestimates the 10- and 15-year risk of SVD compared to cumulative incidence analysis, thus underestimating the benefit of biological valve replacement. Cumulative incidence analysis may lead to a more complete evaluation of risk and benefit and thus better patient management.

Receiver operating characteristic curve analysis of clinical risk models.

Receiver operating characteristic (ROC) curve analysis is a useful method to measure the ability of a clinical risk model to discriminate between hospital deaths and survivors. Its use in medicine originated as a method for synthesizing the specificity and sensitivity of diagnostic tests across a spectrum of possible cut points. The area under the ROC curve can be interpreted as a probability of correct classification or prediction. We illustrate its use in three steps: first, with a dichotomous variable to introduce specificity and sensitivity; next, with a categorical risk factor (surgical urgency) to produce a primitive ROC curve; and finally, with a continuous risk factor (age) to approximate the usual ROC curve used for clinical risk models.

Interpretation of nonfatal events after cardiac surgery: actual versus actuarial reporting.

OBJECTIVE: To describe the cumulative incidence (actual) method of analysis and to contrast it with the Kaplan-Meier method. METHOD: We use data on porcine valve replacement to illustrate these two statistical techniques. RESULTS: The "actual" analysis estimates the percentage of events expected to occur. The percentage given by the Kaplan-Meier method is much larger. CONCLUSION: Actual (cumulative incidence) analysis is preferred for estimating the probability of occurrence of a nonfatal time-related event.

Actuarial and actual analysis of surgical results: empirical validation.

This report validates the use of the Kaplan-Meier (actuarial) method of computing survival curves by comparing 12-year estimates published in 1978 with current assessments. It also contrasts cumulative incidence curves, referred to as "actual" analysis in the cardiac-related literature with Kaplan-Meier curves for thromboembolism and demonstrates that with the former estimate the percentage of events that will actually occur.

Twenty years' experience with the Medtronic Hall valve.

OBJECTIVE: To assess the performance of the Medtronic Hall valve (Medtronic, Inc, Minneapolis, Minn) in one institution over a 20-year period. METHODS: Since 1979, Medtronic Hall valves have been used in 1766 procedures (736 aortic, 796 mitral, and 234 double). Patients were followed up prospectively at 6- to 12-month intervals for a total of 12,688 follow-up years. Anticoagulation data (international normalized ratio) were recorded for all patients (approximately 95,000 observations). RESULTS: Linearized rates of valve-related late death for aortic, mitral, and double valve replacement were 0.8%/y, 0.9%/y, and 1.1%/y, respectively. Risk factors for late mortality were (relative risk) diabetes (1.9), decade of age (1.6), concomitant coronary artery bypass grafting (1.4), hypertension (1.3), non-sinus rhythm (1.3), large valve size (1.1), valve regurgitation (1.3), and male sex (1.2). For aortic, mitral, and double valve replacement, linearized rates (percent per year) of adverse events were valve thrombosis 0.04, 0.03, and 0.0; all thromboembolism 2.3, 4.0, and 3.4; stroke 0.6, 0.8, and 0.6; major hemorrhage 1.2, 1.4, and 1.6; and prosthetic endocarditis 0.4, 0.4, and 0.7. Risk factors for thromboembolism were (relative risk) mitral valve replacement (1.9), diabetes (1.8), hypertension (1.5), and history of embolism (1.4). CONCLUSION: At 20 years the Medtronic Hall valve demonstrates excellent durability, good hemodynamic performance, and very low thrombogenicity, with a valve thrombosis rate lower than those reported for bileaflet designs. With this prosthesis, both survival and thromboembolic events are predominantly determined by patient risk factors.

Estimated event-free life expectancy after autograft aortic root replacement in adults.

BACKGROUND: Autograft aortic root replacement is an established therapeutic option for young adults with aortic valve disease. Unfortunately, most series are small with a limited follow-up. Meta-analysis and microsimulation modeling were used to predict long-term outcome based on currently available midterm data. METHODS: We combined our center's experience with autograft aortic root replacement in 85 adult patients in a meta-analysis with reported results of three other hospitals. The outcomes of this meta-analysis were entered in a microsimulation model, calculating (event-free) life expectancy after autograft aortic root replacement. RESULTS: The pooled results comprised 380 patients with a total follow-up of 1,077 patient-years. Mean age was 37 years (range 16 to 68 years). Male/female ratio was 2.7. Operative mortality was 2.6% (n = 10); during follow-up 6 more patients died. Linearized annual risk estimates were 0.5% for thromboembolism, 0.3% for endocarditis, and 0.4% for nonstructural valve failure. Structural autograft failure requiring reoperation occurred in 5 patients, and a Weibull function was constructed accordingly. Using this information, the microsimulation model predicted age- and gender-specific mean, reoperation-free, and event-free life expectancy. CONCLUSIONS: Based on current evidence the calculated average autograft-related reoperation-free life expectancy is 16 years. The combination of meta-analysis and microsimulation provides a promising and powerful tool for estimating long-term outcome after aortic valve replacement.

Intermediate-term results with 1,019 carbomedics aortic valves.

BACKGROUND: A retrospective study was conducted to evaluate the intermediate-term outcome in patients with the Carbomedics aortic valve prosthesis. METHODS: The study included 1,019 primary valve replacements between 1989 and 1997. Seventy-two percent of patients were men; mean (standard deviation) age was 61 (10) years. The preoperative New York Heart Association functional class was III or IV in 70% of patients. Follow-up at 9 years was 99.6% complete, comprising 2,730 patient-years (mean, 2.7 years). RESULTS: Patient survival, including operative deaths, was 80% at 7 years. The linearized death rate was 2.9%/year. Statistically significant risk factors for mortality were diabetes, pure valve insufficiency, advanced age at operation, and advanced preoperative functional class. Linearized rates were thrombosis, 0.1%/year; thromboembolism, 1.0%/year; hemorrhage, 1.7%/year; endocarditis, 0.1%/year; paravalvular leak, 0.1%/year; reoperation, 0.1%/year; and all events, 3.0%/year. The 7-year estimates of freedom from complications were thrombosis, 99%; thromboembolism, 93%; hemorrhage, 89%; endocarditis, 99%; paravalvular leak, 99.7%; reoperation, 99%; and all events, 82%. No structural valve failure was observed. CONCLUSIONS: The low incidence of valve-related complications favors the continued use of the Carbomedics valve in the aortic position.

Hospital readmission after pulmonary resection: prevalence, patterns, and predisposing characteristics.

BACKGROUND: Our objective was to define the prevalence, patterns, and predisposing characteristics for hospital readmission after pulmonary resection. METHODS: Five years of pulmonary resections, excluding lung biopsies, were analyzed from a prospective, computerized database. Readmission was defined as inpatient or emergency department admission within 90 days of operation. Search of 1,173,912 admissions to the Providence Health System in Oregon identified readmissions. Readmission analysis excluded operative deaths. RESULTS: A total of 374 patients underwent pulmonary resections, of whom 8 died (2.1%). Of 366 patients discharged, 69 (18.9%) were readmitted a total of 113 times: 42 had only one readmission, 16 had two readmissions, 7 had three readmissions, 2 had four readmissions, and 2 had five readmissions. Slightly more than half (51%) were readmitted as inpatients. Causes of the 113 readmissions included pulmonary (27%), postoperative infection (14%), cardiac (7%), and other (16%). Mean time to readmission was 32.5 +/- 24.6 days. Inpatient readmission mean length of stay was 4.9 +/- 3.4 days. Readmission to hospitals other than the hospital of the operation was as follows: first readmission, 15.9%; second readmission, 14.8%; third readmission, 36.3%; fourth readmission, 25%; fifth readmission, 0%. Analysis revealed only pneumonectomy as a risk for readmission. Twelve of 33 (36%) pneumonectomies were readmitted (p = 0.005). Of the 297 patients discharged after pulmonary resection and not requiring readmission, 12 (4%) died over the study interval, whereas 8 of 69 patients (11.6%) requiring readmission died. CONCLUSIONS: Readmission after pulmonary resection is frequent and multiple readmissions are common. Causes are predominately pulmonary diagnoses and infections related to the operation. Pneumonectomy is a risk for readmission. An important portion of readmissions occurs outside the hospital of operation. The population requiring readmission after successfully undergoing pulmonary resection is at increased risk of subsequent mortality.

Survival advantage of stentless aortic bioprostheses.

BACKGROUND: Bioprostheses (BPs) are used to avoid anticoagulation after aortic valve replacement (AVR) in patients over 65 years of age. Stentless BPs offer established hemodynamic benefits. We sought to determine whether these advantages translate into improved survival. METHODS: Between 1993 and 1997, follow-up data (for Food and Drug Administration submission) were collected prospectively for 160 consecutive, unselected hospital survivors who received the Freestyle valve (FS). Equivalent data were collected for 247 Carpentier-Edwards (CE) porcine xenograft patients. Detailed comparative statistical analysis was used to compare events and survival between the groups. Follow-up was 100% complete for the FS (5.2 years maximum; mean 3.2+/-1.0 years) group and 98% (7.2 years maximum; mean 3.8+/-2.0 years) for CE. RESULTS: The groups were well matched in age (FS, 73+/-6 years; CE, 74+/-6 years), gender (FS, 58% male; CE, 62% male), ventricular function, and number of patients requiring coronary grafts (FS, 41%; CE, 37%). Actuarial survival at 5 years was 84% for FS versus 69% for CE (p = 0.023 Kaplan Meier, p = 0.009 Cox). Annual mortality rates were 3.6% for FS versus 7.1% for CE (p = 0.001). Thromboembolic rate was 0.8% per year for FS and 2.4% for CE (p = 0.024) without a difference in cardiac rhythm. Incidence of nonstructural dysfunction (paravalvular leak) was 0.2% for FS versus 1.3% for CE (p = 0.020). CONCLUSIONS: By 5 years, the stentless valve patients had improved survival and reduced adverse events. Though differences in durability are yet to be proved, our findings support the use of stentless bioprostheses in this age group.

Median sternotomy versus thoracotomy to resect primary lung cancer: analysis of 815 cases.

BACKGROUND: We sought to determine if median sternotomy (MS) is an equivalent incision to thoracotomy (TH) in the treatment of primary pulmonary carcinoma. METHODS: We followed 801 patients undergoing 815 operations for primary lung carcinoma in a computer registry; 447 had MS, 368 had TH. RESULTS: Both groups were similar in preoperative risk assessment. Complete staging lymph node dissections were performed in 42% of MS patients and 17% of TH patients. Operative mortality (3.8% for MS, 3.3% for TH) and postoperative complications were similar. MS patients had a shorter postoperative hospital stay (7.5 days vs. 8.2 days). One hundred thirty-nine underwent pneumonectomy. Operative mortality was 12.5% for MS and 10.4% for TS (p = NS). Five hundred eighty-one underwent lobectomy with an operative mortality of 2.1% for MS and 2.0% for TH. Mean length of stay for MS lobectomy was 7.5 days compared with 8.5 days for TH (p = 0.06). Follow-up was 89% through 1998, comprising 1,339 MS and 1,463 TH patient-years. Survival for stage I at 5 and 10 years, respectively, was 51% and 34% for MS vs 54% and 32% for TH (p = NS). Survival for other stages was also similar. CONCLUSIONS: Median sternotomy provides more complete staging, shorter postoperative hospitalization, and better patient acceptance with equivalent operative and long-term survival when compared with thoracotomy. Concerns regarding increased wound infections in MS patients appear unfounded.

Prosthetic valve type for patients undergoing aortic valve replacement: a decision analysis.

BACKGROUND: In two large, randomized, clinical trials long-term survival after aortic valve replacement (AVR) was similar for patients receiving tissue and mechanical aortic heart valve prostheses. Higher bleeding rates among patients with mechanical valves, who must receive permanent oral anticoagulation to prevent thromboembolism, were offset by higher reoperation rates for valve degeneration among patients with tissue valves. Because the average age of patients undergoing AVR and clinical practices have changed considerably since the randomized clinical trials were conducted, we performed a decision analysis to reassess the optimal valve type for patients undergoing AVR. METHODS: We used a Markov state-transition model to simulate the occurrence of valve-related events and life expectancy for patients undergoing AVR. Probabilities of clinical events and mortality were derived from the randomized clinical trials and large follow-up studies. RESULTS: Although the two valve types were associated with similar life expectancy in 60-year-old patients (mean age of patients in the randomized clinical trials), tissue valves were associated with greater life expectancy than mechanical valves (10.7 versus 11.1 years) in 70-year-old patients (currently mean age of AVR patients). For 70-year-old patients, the effects of major bleeding complications (24%) with mechanical valves substantially outweighed those of reoperation for valve failure (12%) with tissue valves at 12 years. Of the clinical practice changes assessed, the recommended valve type was most sensitive to changes in bleeding rates with anticoagulation. However, bleeding rates would have to be 68% lower than those reported in the European randomized clinical trial to affect the recommended valve type for 70-year-old patients. Reoperation rates would have to be five times higher, and mortality rates at reoperation would have to be four times higher to affect the recommended valve type for 70-year-old patients. CONCLUSIONS: Although mechanical valves are preferred for AVR patients less than 60 years old, most patients currently undergoing AVR are elderly and would benefit more from tissue valves.

Risks of spontaneous injury and extraction of an active fixation pacemaker lead: report of the Accufix Multicenter Clinical Study and Worldwide Registry.

BACKGROUND: The Telectronics Accufix pacing leads were recalled in November 1994 after 2 deaths and 2 nonfatal injuries were reported. This multicenter clinical study (MCS) of patients with Accufix leads was designed to determine the rate of spontaneous injury related to the J retention wire and results of lead extraction. METHODS AND RESULTS: The MCS included 2589 patients with Accufix atrial pacing leads that were implanted at or who were followed up at 12 medical centers. Patients underwent cinefluoroscopic imaging of their lead every 6 months. The risk of J retention wire fracture was approximately 5.6%/y at 5 years and 4.7%/y at 10 years after implantation. The annual risk of protrusion was 1.5%. A total of 40 spontaneous injuries were reported to a worldwide registry (WWR) that included data from 34 672 patients (34 892 Accufix leads), including pericardial tamponade (n=19), pericardial effusion (n=5), atrial perforation (n=3), J retention wire embolization (n=4), and death (n=6). The risk of injury was 0.02%/y (95% CI, 0.0025 to 0. 072) in the MCS and 0.048%/y (95% CI, 0.035 to 0.067) in the WWR. A total of 5299 leads (13%) have been extracted worldwide. After recall in the WWR, fatal extraction complications occurred in 0.4% of intravascular procedures (16 of 4023), with life-threatening complications in 0.5% (n=21). Extraction complications increased with implant duration, female sex, and J retention wire protrusion. CONCLUSIONS: Accufix pacing leads pose a low, ongoing risk of injury. Extraction is associated with substantially higher risks, and a conservative management approach is indicated for most patients.

Heart valve replacement: a statistical review of 35 years' results.

BACKGROUND AND AIMS OF THE STUDY: Having performed our first heart valve replacement in 1960, we began a prospective lifetime follow up service for all patients, contacting them at least annually to determine survivorship and heart valve complications. METHODS: We reviewed isolated aortic (AVR) and mitral (MVR) valve replacements from 1960 to 1993, with follow up to 1998. In total, 2,942 AVR and 1,579 MVR were performed, with 21,742 and 12,142 patient-years of follow up, respectively. Analysis of the results affords an opportunity to demonstrate the usefulness and necessity of certain statistical methods, including multivariable event-free analyses and cumulative incidence functions. RESULTS: The survival rate was 8% at 30 years for both valve positions. However, an overall survival curve is an artificial composite of patients of increasingly higher risk being served during increasingly safer years of calendar time. One result is that, for AVR, age is not a significant univariate risk factor for operative mortality, but is highly significant after accounting for date of surgery using logistic regression. Long-term mortality is higher for tissue valves than for mechanical valves; but mean age is greater (74 versus 57 years), and after accounting for age using Cox regression, mortality is similar for both valve types. Kaplan-Meier analysis estimates thromboembolism occurrences of 85% for AVR and 95% for MVR at 35 and 34 years, respectively, but the cumulative incidence estimates are only 32% and 41%, respectively. CONCLUSIONS: Prospective follow up for over 35 years has provided an opportunity to illustrate important statistical issues: Multivariate analyses are essential to avoid being misled by excluding important risk factors or including artifactual ones, and the cumulative incidence estimates the percentage of patients who will actually experience a complication.