Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries is a complex lesion with a high rate of natural attrition. We evaluated the outcomes of our strategy of unifocalization in the management of these patients.
From 1989 to 2008, 216 patients entered a pathway aiming for complete repair by unifocalizing major aortopulmonary arteries to a right ventricle-pulmonary artery conduit with ventricular septal defect closure. Where ventricular septation was not possible, definitive repair was considered to include pulmonary artery reconstruction and a right ventricle-pulmonary artery conduit or systemic shunt. Native pulmonary artery morphology was classified into confluent intrapericardial (n = 139), confluent intrapulmonary (n = 51), and nonconfluent intrapulmonary (n = 26).
A total of 203 patients (85%) had definitive repair at a median age of 2.0 years. There was no statistically significant difference in survival after complete repair among the 3 morphologic pulmonary artery groups (P = .18). A total of 132 patients (56%) had complete repair with ventricular septal defect closure, as a single procedure in 111 patients and a staged procedure in 21 patients. Focalization of major aortopulmonary collateral arteries with proven long-term patency with the right ventricle was associated with a survival benefit compared with 14 patients in whom unifocalization was not possible and who had only systemic shunts. Overall survival was 89% at 3 years after definitive repair. During follow-up, 190 patients required 196 catheter reinterventions and 60 surgical reinterventions.
By using a strategy of unifocalization, intrapericardial pulmonary artery reconstruction, and right ventricle-pulmonary artery conduit, excellent long-term survival can be achieved in this group of patients even in the absence of native intrapericardial pulmonary arteries.
Borderline left heart disease is characterized by left heart obstructive lesions (coarctation, aortic and mitral stenoses, left ventricular hypoplasia) and endocardial fibroelastosis. The multilevel obstruction and impaired left ventricular systolic and diastolic function contribute to failure of biventricular circulation. We studied the effects of left ventricular rehabilitation—endocardial fibroelastosis resection with mitral or aortic valvuloplasty—on left ventricular function and clinical outcomes.
All patients with borderline left heart structures and endocardial fibroelastosis who underwent a primary left ventricular rehabilitation procedure were retrospectively analyzed to determine operative mortality, reintervention rates, and hemodynamic status. Left heart dimensions and hemodynamics were recorded from preoperative and postoperative echocardiogram and cardiac catheterization. Postoperative left atrial pressure was obtained from the intracardiac line early after left ventricular rehabilitation. Preoperative and postoperative values were compared by paired t test.
Between 1999 and 2008, 9 patients with endocardial fibroelastosis and borderline left heart disease underwent left ventricular rehabilitation at a median age of 5.6 months (range, 1–38 months). There was no operative mortality, and at a median follow-up of 25 months (6 months to 10 years) there was 1 death from noncardiac causes and 2 patients required reoperations. Significant increases in ejection fraction and left ventricular end-diastolic volume were observed, whereas left atrial pressure and right ventricular/left ventricular pressure ratios decreased postoperatively.
In patients with borderline left hearts, primary left ventricular rehabilitation with endocardial fibroelastosis resection and mitral and aortic valvuloplasty results in improved left ventricular systolic and diastolic performance and decreased right ventricular pressures. This approach may provide an alternative to single-ventricle management in this difficult patient group.
The common arterial trunk usually has a balanced origin from both right and left ventricles overriding a ventricular septal defect. The trunk occasionally originates predominantly, or even exclusively, from either ventricle, making the size of the ventricular septal defect an important factor in surgical repair.
We examined 56 autopsy specimens and reviewed another series of 12 consecutive patients with the malformation. Truncal origin was categorized as 1 of the following 5 types: exclusive origin from either the right or left ventricle, predominant origin from either ventricle, or balanced origin. We measured the size of ventricular septal defect ("width" and "depth") in specimens for any correlation with truncal origin.
Balanced origin was seen in approximately one half of cases in both autopsy and clinical series. Predominantly or exclusively right ventricular origin was more prevalent than left ventricular origin in autopsy series (40% vs 9%, respectively), but such predilection was not observed in clinical series (both 25%). The more the truncal valve was committed to the right ventricle, the smaller was the "width" of the ventricular septal defect (predominant and exclusive vs balanced origin; both P < .0001), with similar tendency in the "depth." In 1 heart with extreme right ventricular origin, the defect was slit-like.
Origin of the truncal valve demonstrated a morphologic spectrum and correlated with the size of ventricular septal defect that was the main or even sole exit from the left ventricle in hearts with right ventricular origin. Truncal origin, therefore, requires recognition to optimize surgery.
Our objective was to compare protein profiles of cerebrospinal fluid between control animals and those subjected to cardiopulmonary bypass after moderate versus deep hypothermic circulatory arrest with selective cerebral perfusion.
Immature Yorkshire piglets were assigned to one of four study groups: (1) deep hypothermic circulatory arrest at 18°C, (2) deep hypothermic circulatory arrest at 18°C with selective cerebral perfusion, (3) moderate hypothermic circulatory arrest at 25°C with selective cerebral perfusion, or (4) age-matched control animals without surgery. Animals undergoing cardiopulmonary bypass were cooled to their assigned group temperature and exposed to 1 hour of hypothermic circulatory arrest. After arrest, animals were rewarmed, weaned off bypass, and allowed to recover for 4 hours. Cerebrospinal fluid collected from surgical animals after the recovery period was compared with cerebrospinal fluid from controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein spectra were analyzed for differences between groups by Mann–Whitney U test and false discovery rate analysis.
Baseline and postbypass physiologic parameters were similar in all surgical groups. A total of 194 protein peaks were detected. Compared with controls, groups 1, 2, and 3 had 64, 100, and 13 peaks that were significantly different, respectively (P < .05). Three of these peaks were present in all three groups. Cerebrospinal fluid protein profiles in animals undergoing cardiopulmonary bypass with moderate hypothermic circulatory arrest (group 3) were more similar to controls than either of the groups subjected to deep hypothermia.
The mass spectra of cerebrospinal fluid proteins are altered in piglets exposed to cardiopulmonary bypass and hypothermic circulatory arrest. Moderate hypothermic circulatory arresst (25°C) with selective cerebral perfusion compared with deep hypothermic circulatory arrest (18°C) is associated with fewer changes in cerebrospinal fluid proteins, when compared with nonbypass controls.
Diffusing capacity is not routinely used in assessing risk of lung resection, perhaps owing to uncertainty as to whether patients with normal spirometric results require additional evaluation. We determined whether diffusing capacity is predictive of pulmonary complications after lung resection in patients with normal spirometric results.
We reviewed outcomes of major lung resection in The Society of Thoracic Surgeons General Thoracic Surgery Database from 2002 to 2008 to determine the relationship of diffusing capacity (expressed as percent of predicted) to postoperative pulmonary complications stratified by chronic obstructive pulmonary disease status.
Percent of predicted diffusing capacity was measured in 7891 (57%) patients. There were 3905 women and 3986 men with a mean age of 66.3 ± 10.6 years who underwent lobectomy (6904; 87.5%), bilobectomy (463; 5.9%), and pneumonectomy (524; 6.6%). Chronic obstructive pulmonary disease was identified in 2711 (34.4%) patients. Pulmonary complications occurred in 13%, and the operative mortality was 1.9%. Percent of predicted diffusing capacity was strongly associated with the development of pulmonary complications (odds ratio, 1.12 per 10-point decrease; P < .0001). Decreasing percent of predicted diffusing capacity was incrementally related to an increased incidence of pulmonary complications regardless of chronic obstructive pulmonary disease status. There was no apparent interaction between percent of predicted diffusing capacity and chronic obstructive pulmonary disease status in the predictive model.
Percent of predicted diffusing capacity predicts pulmonary complications after lung resection in patients without chronic obstructive pulmonary disease. We recommend measurement of diffusing capacity in lung resection candidates, regardless of chronic obstructive pulmonary disease, as an important element in the accurate assessment of operative risk.
We investigated the possibility of DYRK2, a dual-specificity tyrosine-(Y)-phosphorylation–regulated kinase gene, to predict survival for patients with pulmonary adenocarcinoma.
One hundred forty-four patients with pulmonary adenocarcinoma underwent surgery in our institute from 2000 to 2008. We used immunohistochemical analysis and real-time reverse-transcriptase polymerase chain reaction to determine the expression of DYRK2 and compared this with the clinicopathologic factors and survival.
We found no correlation between DYRK2 expression by immunohistochemical and clinicopathologic factors; however, a negative nodal status and negative lymphatic invasion were significantly associated with DYRK2 expression by reverse-transcriptase polymerase chain reaction. Five-year disease-free survival in the DYRK2-positive group (75.4%) was significantly different from that in the negative group (55.4%; P = .03) by immunohistochemical analysis. The 5-year overall survival of 89.2% in the DYRK2-positive group was better than the 66.3% survival of the DYRK2-negative group (P = .01). Quantitative real-time reverse-transcriptase polymerase chain reaction analyses showed a significant difference between positive and negative expressions for disease-free survival (P = .003) and overall survival (P = .007). In multivariate Cox regression analysis, negative DYRK2 protein and messenger RNA expression showed a worse prognostic value of survival (hazard ratio [HR] = 4.7, 95% confidence intervals [CI] = 1.5–14.5, P=.007; HR = 2.5, 95% CI = 1.1–6.1, P = .04, respectively). When we analyzed adenocarcinoma cases except for bronchioloalveolar carcinoma, we found a close correlation between DYRK2 expression by immunohistochemical analysis and nodal status (P = .03). Furthermore, disease-free survivals between positive and negative groups of DYRK2 expression by immunohistochemistry (P = .03) and reverse-transcriptase polymerase chain reaction (P = .02) without bronchioloalveolar carcinoma were significantly different. Overall survivals in both groups showed significant differences by immunohistochemistry (P = .02) but not by reverse-transcriptase polymerase chain reaction (P = .08).
These data showed that DYRK2 expression is associated with a favorable prognosis.
We hypothesized that most relapses in patients with esophageal cancer having neoadjuvant chemoradiation therapy would occur outside of the surgical and radiation fields.
Recurrence patterns, time to recurrence, and median survival were examined in 267 patients who had esophagectomy after neoadjuvant chemoradiation therapy at Johns Hopkins over 19 years.
Of 267 patients, 82 (30.7%) showed complete response to neoadjuvant therapy, with 108 (40.4%) and 77 (28.8%) showing partial response or no response, respectively. Recurrence developed in 84 patients (patients with complete response 18/82, 21.4%; patients with partial response 39/108, 36.1%; patients with no response 27/77, 35.1%; P = .055, respectively). Most patients had recurrences at distant sites (65/84;77.4%) regardless of pathologic response, and subsequent survival was brief (median 8.37 months). Median disease-free survival was short (10 months) and did not differ based on recurrence site for patients with partial response or no response, but was longer for patients with complete response with distant recurrence, whose median disease-free survival was 27.3 months (P = .008). By multivariate analysis, no other factor except for pathologic response to neoadjuvant therapy was associated with disease recurrence or death. Patients with partial response or no response were 1.97 and 2.23 times more likely to have recurrence than patients with complete response (P = .024 and P = .012, respectively).
Most esophageal cancer recurrences after neoadjuvant therapy and surgery are distant, and survival time after recurrence is short regardless of pathologic response. Fewer patients achieving complete response had recurrences, and distant recurrences in these patients manifest later than in patients showing partial response and those showing no response. Only pathologic response is significantly associated with disease recurrence, suggesting that tumor biology and chemosensitivity are critical in long-term patient outcome.
Anatomic segmentectomy is increasingly being considered as a means of achieving an R0 resection for peripheral, small, stage I non–small-cell lung cancer. In the current study, we compare the results of video-assisted thoracic surgery (n = 104) versus open (n = 121) segmentectomy in the treatment of stage I non–small-cell lung cancer.
A total of 225 consecutive anatomic segmentectomies were performed for stage IA (n = 138) or IB (n = 87) non–small-cell lung cancer from 2002 to 2007. Primary outcome variables included hospital course, complications, mortality, recurrence, and survival. Statistical comparisons were performed utilizing the t test and Fisher exact test. The probability of overall and recurrence-free survival was estimated with the Kaplan-Meier method, with significance being estimated by the log-rank test.
Mean age (69.9 years) and gender distribution were similar between the video-assisted thoracic surgery and open groups. Average tumor size was 2.3 cm (2.1 cm video-assisted thoracic surgery; 2.4 cm open). Mean follow-up was 16.2 (video-assisted thoracic surgery) and 28.2 (open) months. There were 2 perioperative deaths (2/225; 0.9%), both in the open group. Video-assisted thoracic surgery segmentectomy was associated with decreased length of stay (5 vs 7 days, P < .001) and pulmonary complications (15.4% vs 29.8%, P = .012) compared with open segmentectomy. Overall mortality, complications, local and systemic recurrence, and survival were similar between video-assisted thoracic surgery and open segmentectomy groups.
Video-assisted thoracic surgery segmentectomy can be performed with acceptable morbidity, mortality, recurrence, and survival. The video-assisted thoracic surgery approach affords a shorter length of stay and fewer postoperative pulmonary complications compared with open techniques. The potential benefits and limitations of segmentectomy will need to be further evaluated by prospective, randomized trials.
The objective of this study was to find the best treatment strategy in patients who had acute coronary syndrome and ST-segment elevation myocardial infarction sustaining cardiogenic shock.
Patients having cardiogenic shock owing to acute coronary syndrome and ST-segment elevation myocardial infarction who required hemodynamic support with intra-aortic balloon counterpulsation were retrospectively retrieved from the clinical information system in a tertiary medical center in Taiwan. A propensity score–based matching process was applied to find equalized groups with documented involvement of more than 2 coronary vessels who received percutaneous coronary intervention only (PCI only group) and who underwent subsequent coronary artery bypass graft surgery after percutaneous coronary intervention (PCI+CABG group). A logistic regression model was used to find the factors associated with 30-day mortality.
The propensity analysis identified 44 patients in the PCI only group (35 men, 65 ± 2 years, and 9 women, 75 ± 4 years) and the other 44 patients in the PCI+CABG group (31 men, 67 ± 2 years, and 13 women, 71 ± 2 years) who had comparable baseline characteristics. The 30-day mortality, 40.9% in the PCI only group and 20.5% in the PCI+CABG group, was positively associated with percutaneous coronary intervention only (odds ratio, 3.33; 95% confidence intervals, 1.14–10.0; P = .03), increased age (odds ratio, 1.06 for each year; 95% confidence intervals, 1.01–1.12; P = .01) and a need to use extracorporeal membrane oxygenation (odds ratio, 9.64; 95% confidence intervals, 2.19–42.4; P < .001).
This study has shown the survival benefit of surgical intervention in high-risk patients with acute coronary syndrome or ST-segment elevation myocardial infarction who had cardiogenic shock after percutaneous coronary intervention.
We sought to report our experience with combined retrograde visceral revascularization and endovascular exclusion (hybrid procedure) of thoracoabdominal aortic aneurysms.
From February 2005 to October 2007, the prospectively collected data of 18 consecutive patients undergoing hybrid repair were analyzed. Median age was 73 years; Crawford–Safi extent included 2 type I, 8 type II, 7 type III, and 1 type V thoracoabdominal aortic aneurysms; 13 were atherosclerotic and 5 were postdissecting aneurysms. Previous open or endovascular aortic surgery had been performed in 11 (61.1%) patients. Society for Vascular Surgery/North American Chapter of the International Society for Cardiovascular Surgery preoperative risk stratification identified mild-to-severe hypertension and pulmonary and cardiac status in 88.9%, 67.7%, and 88.9% of the patients, respectively.
Fifty-four visceral vessels were bypassed in 18 patients. As an adequate inflow site, the common iliac artery was identified in 15 (83.3%) patients, the infrarenal native aorta was identified in 1 (5.6%) patient, and a previous tube graft was identified in 2 (11.1%) patients. Median operating time was 360 minutes (range, 210–600 minutes), and median blood loss was 3200 mL (range, 1000–18,000 mL). Aneurysm exclusion was achieved in 17 patients. Thirty-day mortality was 16.7% (n = 3/18). Complications included paraplegia (n = 1) and acute myocardial infarction (n = 2). Median follow-up was 23 months (range, 8–42 months), with visceral graft patency at follow-up or death of 98.1% (n = 53/54). One early and 1 late type Ia endoleak (11.8%, n = 2/17), no type III endoleaks, and 5 type II endoleaks were detected, none necessitating adjuvant procedures.
The visceral hybrid repair is a feasible and relatively safe procedure for extensive thoracoabdominal aortic aneurysms. Even considering the significantly high mortality and morbidity rates, it might represent a viable alternative in a cohort of patients historically deemed at high risk for traditional surgical intervention.
The management of asymptomatic severe mitral regurgitation remains controversial. The aim of the study was to assess the long-term survival, incidence of cardiac complications, factors that predict outcome, and effect of mitral surgery on the long-term prognosis of patients with asymptomatic severe mitral regurgitation amenable to valve repair.
One hundred ninety-two asymptomatic patients (mean age, 63 ± 13 years) with severe degenerative mitral regurgitation diagnosed by 2-dimensional echocardiography between 1990 and 2001 were prospectively followed for a median of 8.5 years.
Overall, cardiovascular, and event-free survival was evaluated in 2 groups of patients: a "conservative approach" group (n = 67) and an "early surgery" group (n = 125). Outcomes were also analyzed among patients with atrial fibrillation, pulmonary hypertension, or both, as well as in patients free of any mitral regurgitation complications. In the whole population, 10-year overall survival was significantly lower with the conservative approach than early surgery (50% ± 7% vs 86% ± 4%, log-rank < 0.0001). Similar results were obtained in the subgroups with atrial fibrillation and/or pulmonary hypertension. The 10-year propensity-matched score-adjusted hazards ratio for overall mortality, cardiac mortality, and cardiovascular events for the conservative treatment were 5.21, 4.83, and 4.40, respectively.
Our results show that the outcome of asymptomatic patients with severe degenerative mitral regurgitation is better with an early surgical approach rather than a more conservative treatment strategy.
We sought to assess early and late survival and cardiovascular-specific mortality after surgical repair of acute ascending aortic dissection and the effect of differences in surgical technique, patient characteristics, and preoperative diagnostic testing.
Between 1979 and 2003, 195 consecutive patients underwent repair for acute ascending aortic dissection within 2 weeks of the onset of symptoms. Mean follow-up was 7.0 ± 5.9 years (range, 0–26 years) and was 100% complete.
Patients were aged 62 ± 15 years on average and were mostly male (66%) and hypertensive (69%). Risk of death early and late after the operation decreased over the study period, with hospital mortality decreasing from 21% to 4% when comparing the first and most recent quartiles (P = .007, 2 test for trend). At 1, 5, 10, and 20 years postoperatively, survival was 84%, 69%, 55%, and 30%, respectively, and freedom from cardiovascular death was 86%, 80%, 71%, and 51%, respectively. Additional independent risk factors for death were older age (P < .001), renal dysfunction (P < .003), syncope (P = .007), and peripheral vascular disease (P = .006). During the study period, echocardiographic and computed tomographic diagnostic imaging replaced routine aortic angiographic analysis, and operative techniques involved more frequent use of open distal anastomoses, retrograde cerebral perfusion, earlier restoration of antegrade perfusion, and a conservative approach to aortic arch repair. Freedom from reoperation on the aorta or aortic valve was 93% and 84% at 5 and 10 years, respectively.
Early and late survival after repair of acute ascending aortic dissection has improved progressively over 25 years in association with noticeable changes in preoperative and intraoperative management. Aortic reoperations were infrequent during follow-up.
In patients with acute type A dissection, it is controversial whether to use a more aggressive strategy with extended aortic replacement to improve long-term outcome or to use a conventional strategy with limited ascending aortic or hemiarch replacement to circumvent a life-threatening situation.
Between April 2003 and June 2007, 107 patients (17 women, 90 men; mean age, 45 ± 11 years; range, 17–78 years) with acute type A dissection underwent total arch replacement combined with stented elephant trunk implantation under hypothermic cardiopulmonary bypass and selective cerebral perfusion. Computed tomography was performed to evaluate the residual false lumen in the descending aorta during follow-up.
Thirty-day mortality was 3.74% (4/107 patients), and in-hospital mortality was 4.67% (5/107 patients). Spinal cord injury was observed in 3 patients (1 patient with left lower-extremity paraparesis and 2 patients with paraplegia). Cerebral infarction was observed in 3 patients, ventilator support exceeding 5 days was required in 9 patients, and rebleeding was observed in 4 patients. During a mean follow-up of 35 ± 14 months, 3 patients died and 3 patients were lost to follow-up. On postoperative computed tomography, complete thrombus formation was observed around the stented elephant trunk in 95% of patients (95/100) and at the diaphragmatic level in 69% of patients (69/100).
Low morbidity and mortality were achieved using total arch replacement combined with stented elephant trunk implantation. These encouraging surgical results and postoperative outcomes favor this more aggressive procedure for acute type A dissection.
Patients who have type A dissection with preoperative malperfusion syndromes are believed to be at extremely high surgical risk. Our aim was to evaluate perioperative and long-term results of patients with preoperative malperfusion.
A total of 276 patients (174 men; mean age 59.5 ± 13.4 years) underwent surgery for acute type A dissection between October 1994 and January 2008. Preoperative malperfusion syndromes were diagnosed in 93 (33.7%) patients (group I) and involved coronary circulation in 41 (15%) patients, central nervous system in 39 (14%) patients, limb ischemia in 32 (11.6%) patients, and mesenteric circulation in 8 (3%) patients. Postoperative results were compared between patients with preoperative malperfusion and those without this complication (group II, n = 183).
In-hospital mortality was 29.0% in group I versus 13.6% in group II (P = .002). The postoperative intensive care unit stay was longer (11.4 ± 9.7 vs 7.7 ± 6.9 days; P = .04) in the malperfusion group. A total of 6 (75%) patients with mesenteric malperfusion died. Long-term follow-up (range, 1–122 months postoperatively) was available in 100% of survivors. One-year and 5-year overall survivals were 49.8% ± 11.8% and 41.8% ± 12.6% in group I versus 70.4% ± 7.6% and 56% ± 10.4% in group II (P = .005). Cox regression analysis identified preoperative malperfusion as a significant risk factor for long-term mortality after surgery for type A dissection (hazard ratio, 1.7; 95% confidence intervals, 1.2–3.1).
Preoperative malperfusion is a significant risk factor influencing perioperative and long-term survival after surgery for acute type A dissection. Percutaneous interventional procedures and delayed surgery should be considered in patients with clinically apparent mesenteric malperfusion because of the dismal prognosis of immediate surgical therapy.
There is an intense debate on whether the RIFLE (R–renal risk, I–injury, F–failure, L–loss of kidney function, E–end-stage renal disease) classification or its recent modification, the Acute Kidney Injury Network definition and classification system should be used to standardize research on acute kidney injury. In this study we compared these classifications with regard to (1) the detection of acute kidney injury, (2) their agreement according to the grading of acute kidney injury across classes, and (3) their prognostic value.
We prospectively enrolled 282 cardiac surgery patients undergoing cardiopulmonary bypass and assigned a RIFLE and Acute Kidney Injury Network class to each patient. The incidence of acute kidney injury and in-hospital mortality across classes was compared by using the 2 test, and their prognostic value was compared by using the area under the curve receiver-operating characteristic for in-hospital mortality.
According to the RIFLE (45.8%) or Acute Kidney Injury Network (44.7%) classification, a similar proportion of patients had acute kidney injury. There was large agreement between classifications according to patients graded as having nonacute kidney injury; however, there was some disagreement across classes for staging the severity of acute kidney injury. The area under the curve for in-hospital mortality was similar for all classifications: 0.91 for the RIFLE classification (95% confidence interval, 0.82–0.99) and 0.94 for the Acute Kidney Injury Network classification (95% confidence interval, 0.81–0.97; P = .6 for area under the curve comparison).
In patients undergoing cardiac surgery, modifications of the RIFLE classification for acute kidney injury do not materially improve the clinical usefulness of the definition. Other factors, such as the applicability of the acute kidney injury definition and classification system to be applied, need to be considered.
Preoperative use of clopidogrel increases the risk of bleeding, but its postoperative use has not been studied. We studied early postoperative clopidogrel use in on-pump and off-pump coronary artery bypass grafting.
Data were obtained from the University HealthSystem Consortium database. We conducted a retrospective analysis of data of 15,067 adults who had coronary artery bypass grafting between 2003 and 2006 and received perioperative aspirin alone or in combination with clopidogrel, with the latter administered within 2 days after coronary artery bypass grafting. Logistic regression was used to analyze in-hospital mortality, 30-day readmission, ischemic or thrombotic events, and bleeding events, with propensity score adjustment for clopidogrel treatment.
Combined aspirin and clopidogrel were used in 3268 patients (22%). Compared with aspirin alone, aspirin plus clopidogrel was associated with reductions of in-hospital mortality (0.95% vs 1.78%; adjusted odds ratio: 0.50; 95% confidence interval: 0.25, 0.99) and bleeding events (4.19% vs 5.17%; adjusted odds ratio: 0.70; 95% confidence interval: 0.51, 0.97). Ischemic or thrombotic events were not significantly different (1.29% vs 1.53%; adjusted odds ratio, 0.99; 95% confidence interval: 0.59, 1.64). The relative effect of combined treatment did not differ between on-pump and off-pump coronary artery bypass grafting.
Early postoperative clopidogrel combined with aspirin may be safe and beneficial compared with perioperative aspirin treatment alone, in both on-pump and off-pump coronary artery bypass grafting. However, a possibility of selection bias calls for randomized controlled trials to confirm our findings.
Neutrophils are crucial in the development of acute lung injuries during cardiopulmonary bypass. However, the efficacy of leukocyte depletion on pulmonary protection remains controversial, possibly owing to different filtration strategies used in the literature. In this study, we investigated whether short-term leukocyte depletion strategy is more efficacious than prolonged leukocyte depletion in preserving pulmonary function.
Eighteen adult dogs were randomized equally into 3 groups. Leukocyte-depleting filters were used for 10 minutes in the LD-S group, throughout cardiopulmonary bypass in the LD-T group, and not used in the control group. Neutrophil counts, elastase, and interleukin-8 concentrations in plasma, myeloperoxidase and interleukin-8 concentrations in pulmonary tissue, and pulmonary vascular resistance and oxygen index were determined to evaluate the inflammatory response and damage to pulmonary function.
Although the neutrophil count and pulmonary parenchymal myeloperoxidase contents were significantly lower in both LD-S and LD-T groups than that in the control group, lower pulmonary parenchymal interleukin-8 level, lower pulmonary vascular resistance (113 ± 33 dyne · s/cm5), higher oxygen index (366 ± 82.3 mm Hg), and thinner alveolus wall thickness were seen only in the LD-S group, and the pulmonary parenchymal interleukin-8 levels were also lower in the LD-S group after cardiopulmonary bypass. The plasma elastase and interleukin-8 levels were significantly lower in the LD-S group, but they were significantly higher in the LD-T group compared with the control group after cardiopulmonary bypass.
Short-term rather than prolonged leukocyte depletion during cardiopulmonary bypass appears to be more efficacious in protecting pulmonary function via attenuation of the extracorporeal circulation–induced inflammatory response.
Vascular smooth muscle cells can undergo profound changes in phenotype, defined by coordinated repression of smooth muscle cell marker genes and production of matrix metalloproteinases in response to injury. However, little is known of the role of smooth muscle cells in aortic aneurysms. We hypothesized that smooth muscle cells undergo phenotypic modulation early in the development of aortic aneurysms.
Abdominal aortas from C57B6 mice (n = 79) were perfused with elastase or saline (control) and harvested at 1, 3, 7, or 14 days. Aortas were analyzed by means of quantitative polymerase chain reaction and immunohistochemistry for smooth muscle cell marker genes, including SM22A, smooth muscle -actin, and matrix metalloproteinases 2 and 9. In complimentary experiments human aneurysms (n = 10) and control aorta (n = 10) were harvested at the time of surgical intervention and analyzed.
By 14 days, aortic diameter was larger after elastase perfusion compared with control diameter (100% ± 9.6% vs 59.5% ± 18.9%, P = .0002). At 7 days, elastase-perfused mice had a 78% and 85% reduction in SM22 and smooth muscle -actin expression, respectively, compared with that seen in control animals well before aneurysms were present, and these values remained repressed at 14 days. Immunohistochemistry confirmed less SM22 and smooth muscle -actin in experimental aneurysms at 14 days in concert with increased matrix metalloproteinase 2 and 9 expression at 7 and 14 days. Similarly, human aneurysms had less SM22 and smooth muscle -actin and increased matrix metalloproteinase 2 and 9 staining, compared with control values, as determined by means of quantitative polymerase chain reaction.
Aneurysms demonstrate smooth muscle cell phenotypic modulation characterized by downregulation of smooth muscle cell marker genes and upregulation of matrix metalloproteinases. These events in experimental models occur before aneurysm formation. Targeting smooth muscle cells to a reparative phenotype might provide a novel therapy in the treatment of aortic aneurysms.
The mechanism of the putative beneficial effect of myocardial transplantation of bone marrow cells remains unclear. We studied the protective properties of bone marrow cells on the human myocardium and investigated the underlying mechanism.
Bone marrow cells and the right atrial appendage were obtained from patients undergoing elective cardiac surgery. Myocardial slices were subjected to 90 minutes of simulated ischemia/120 minutes of reoxygenation at 37°C following various protocols. Tissue injury was assessed by creatine kinase released into the media during the reoxygenation period, and myocardial necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (percent of aerobic control).
Autologous unfractionated bone marrow cells significantly reduced myocardial injury. Maximal protection was obtained with 5 x 106 autologous cells (~1.5 x 105 cells/mg wet myocardium) that caused a reduction in creatine kinase release and cell death by necrosis and apoptosis of 70% to 80%. Allogenic bone marrow cells were as protective as the autologous cells and their effect was unaffected by prior frozen storage or culturing. Similar myocardial protection was also attained when bone marrow cells were present only before or during ischemia, or during reoxygenation, a benefit that was comparable with that of ischemic preconditioning. Conditioned media by the bone marrow cells was sufficient to induce protection, which was abolished by the selective insulin-like growth factor-1 receptor blocker PQ401.
Bone marrow cells possess potent myocardial protective properties that are triggered by a secreted factor or factors and mediated by insulin-like growth factor-1 receptor. These results have important clinical implications for the therapeutic use of bone marrow cells in ischemic heart disease and for the design of future clinical studies.
The aim of this study was to examine the influence of endogenous cannabinoids on neuroprotection of the spinal cord afforded by limb remote ischemic preconditioning.
In experiment 1 (RIPC group), 3 cycles of limb remote ischemic preconditioning within different episodes (2, 3, or 5 minutes) were induced before spinal cord ischemia in rats (N = 5, n = 8). In experiment 2, animals were pretreated intravenously by the vehicles, cannabinoid 1 (AM251, 1 mg/kg) or cannaboid 2 (AM630, 1 mg/kg) receptor antagonist 15 minutes before remote ischemic preconditioning, or else they were subjected to a sham operation. Thirty minutes after the pretreatment, spinal cord ischemia was induced (N = 8, n = 8). In experiment 3, the arachidonylethanolamide and 2-arachidonoylglycerol contents in the spinal cord after remote ischemic preconditioning and spinal cord ischemia were detected in rats (N = 2, n = 12). Spinal cord ischemia was induced by 12 minutes of thoracic aorta occlusion in rats. Neurologic function was assessed 24 and 48 hours after reperfusion. Histopathologic examination was performed and the number of normal neurons in anterior spinal cord were counted.
In experiment 1, 3 cycles of limb remote ischemic preconditioning (3 minutes of ischemia/3 minutes of reperfusion) induced ischemic tolerance on the spinal cords of the rats. The RIPC group showed a significant reduction in motor deficit index (P < .01) as well as an increase in the number of normal neurons (P < .01). In experiment 2, the cannabinoid 1 receptor antagonist AM251 pretreatment abolished the protective effects of remote preconditioning. In experiment 3, arachidonylethanolamide content in spinal cord was elevated by remote ischemic preconditioning in rats.
These results indicated that endogenous cannabinoids, through acting on cannabinoid 1 receptors, were involved in the neuroprotective phenomenon on spinal cords of limb remote ischemic preconditioning.
Inhaled nitric oxide has been shown to reduce pulmonary vascular resistance in patients undergoing cardiothoracic surgery, but it is limited by toxicity, the need for special monitoring, and cost. Inhaled prostacyclin also decreases pulmonary artery pressure, is relatively free of toxicity, requires no specific monitoring, and is less expensive. The objective of this study was to compare nitric oxide and prostacyclin in the treatment of pulmonary hypertension, refractory hypoxemia, and right ventricular dysfunction in thoracic transplant recipients in a prospective, randomized, crossover pilot trial.
Heart transplant and lung transplant recipients were randomized to nitric oxide or prostacyclin as initial treatment, followed by a crossover to the other agent after 6 hours. Pulmonary vasodilators were initiated in the operating room for pulmonary hypertension, refractory hypoxemia, or right ventricular dysfunction. Nitric oxide was administered at 20 ppm, and prostacyclin was administered at 20,000 ng/mL. Hemodynamic and oxygenation parameters were recorded before and after initiation of pulmonary vasodilator therapy. At 6 hours, the hemodynamic and oxygenation parameters were recorded again, just before discontinuing the initial agent. Crossover baseline parameters were measured 30 minutes after the initial agent had been stopped. The crossover agent was then started, and the hemodynamic and oxygenation parameters were measured again 30 minutes later.
Heart transplant and lung transplant recipients (n = 25) were randomized by initial treatment (nitric oxide, n = 14; prostacyclin, n = 11). Nitric oxide and prostacyclin both reduced pulmonary artery pressure and central venous pressure, and improved cardiac index and mixed venous oxygen saturation on initiation of therapy. More importantly, at the 6-hour crossover trial, there were no significant differences between nitric oxide and prostacyclin in the reduction of pulmonary artery pressures or central venous pressure, or in improvement in cardiac index or mixed venous oxygen saturation. Nitric oxide and prostacyclin did not affect the oxygenation index or systemic blood pressure. There were no complications associated with nitric oxide or prostacyclin.
In heart transplant and lung transplant recipients, nitric oxide and prostacyclin similarly reduce pulmonary artery pressures and central venous pressure, and improve cardiac index and mixed venous oxygen saturation. Inhaled prostacyclin may offer an alternative to nitric oxide in the treatment of pulmonary hypertension in thoracic transplantation.
The purpose of this study was to compare posttransplantation morbidity and mortality in orthotopic heart transplant recipients bridged to transplant with a left ventricular assist device with nonbridged recipients. To account for potential differences across device types, we stratified bridge-to-transplant recipients by type of ventricular assist device: extracorporeal (EXTRA), paracorporeal (PARA), and intracorporeal (INTRA).
The United Network for Organ Sharing provided de-identified patient-level data. The study population included 10,668 orthotopic heart transplant recipients aged 18 years old or older and undergoing transplantation between January 1, 2001, and December 31, 2006. Follow-up data were provided through August 3, 2008, with a mean follow-up time of 3.17 ± 2.15 years (range, 0–8.11 years). The primary outcome was actuarial posttransplant graft survival. Other outcomes of interest included infection, stroke, and dialysis during the transplant hospitalization; primary graft failure at 30 days; transplant hospitalization length of stay; and long-term complications including diabetes mellitus, transplant coronary artery disease, and chronic dialysis. Multivariable Cox proportional hazards regression (backward, P < .15) was used to determine the relationship between groups and overall graft survival, and multivariable logistic regression analysis (backward, P < .15) was used to determine the relationship between groups and secondary outcome measures.
In multivariable Cox regression analysis, when compared with the nonbridged group, risk-adjusted greater than 90-day graft survival was diminished among the EXTRA group (hazard ratio = 3.54, 2.28–5.51, P < .001), but not the INTRA group (1.04, 0.719–1.51, P = .834) or the PARA group (1.06, 0.642–1.76, P = .809). There were no significant differences in risk-adjusted graft survival across the 4 groups during the 90-days to 1-year or 1- to 5-year intervals. However, at more than 5 years, risk-adjusted graft survival in the INTRA group (0.389, 0.205–0.738, P = .004) was better than in the nonbridged group. The EXTRA, PARA, and INTRA groups all experienced increased risks of infection. The EXTRA group had increased risks of dialysis, stroke, and primary graft failure at 30 days, whereas neither the PARA nor the INTRA group differed from the nonbridged group. Long-term complications did not differ by group.
The use of implantable left ventricular assist devices as bridges to transplantation, including both intracorporeal and paracorporeal devices, is not associated with diminished posttransplant survival. However, 90-day survival was diminished in recipients bridged with extracorporeal devices.