Faculty Bibliography

PURPOSE/OBJECTIVE:Platelet transfusion in cardiac surgery is often empiric as no established point-of-care tests are available for clear guidance of blood product administration, and there are many variables that can potentially increase the risk of bleeding during cardiopulmonary bypass. The objectives of this study were to determine the factors that influenced physicians' decisions to transfuse platelets perioperatively and to determine whether these factors coincide with characteristics using chart abstraction. METHODS:This study was conducted at three university affiliated hospitals using focused physician questionnaires to assess factors influencing decisions to transfuse platelets and data abstraction to determine characteristics of patients receiving platelet transfusion during cardiac surgery. RESULTS:Seventy-six physicians participated in the questionnaire; 41% identified bleeding and 22% identified both bleeding and the platelet count as the most significant factors influencing their decision to transfuse platelets. Of the 629 patients included in the study, 24.5% received a platelet transfusion intraoperatively and 4.5% received the transfusion postoperatively. The following factors were identified with the highest odds of receiving a platelet transfusion intraoperatively: combined bypass and valvular surgery (odds ratio [OR] 3.94; 95% confidence interval [CI] 1.94 to 8.00) and the presence of liver disease (OR 6.43; 95% CI 1.17 to 35.37). CONCLUSION/CONCLUSIONS:The use of focused physician questionnaires identified relevant aspects of patient care not apparent in the chart review that influenced the decision to transfuse platelets. The identification of bleeding, thrombocytopenia, more complex surgery, and the presence of liver disease highlights the requirement for standardized measures to assess the need for platelet transfusions in bleeding patients.

OBJECTIVES/OBJECTIVE:The management strategy remains controversial for patients presenting with type A acute aortic dissection with cerebrovascular accident or coma. The present study aimed to help guide surgeons treating these high-risk patients. METHODS:Of 1873 patients with type A acute aortic dissection enrolled in the International Registry for Acute Dissection, 87 (4.7%) presented with cerebrovascular accident and 54 (2.9%) with coma. The hospital and 5-year results were stratified by the presence and type of brain injury (no injury vs stroke vs coma) and management type (medical vs surgical). Independent predictors of short- and mid-term survival were identified. RESULTS:Presentation with shock, hypotension, or tamponade (46.8% vs 25.2%; P < .001) and arch vessel involvement (55.0% vs 36.1%; P < .001) was more likely in patients with brain injury. Surgical management was avoided more often in patients with coma (33.3%) or cerebrovascular accident (24.1%) than in those without brain injury (11.1%; P < .001). The overall hospital mortality was 22.7% without brain injury, 40.2% with cerebrovascular accident, and 63.0% with coma (P < .001). Mortality varied among the management types for both cerebrovascular accident (76.2% medical vs 27.0% surgical; P < .001) and coma (100% medical vs 44.4% surgical; P < .001). Postoperatively, cerebrovascular accident and coma resolved in 84.3% and 78.8% of cases, respectively. On logistic regression analysis, surgery was protective against mortality in patients presenting with brain injury (odds ratio 0.058; P < .001). The 5-year survival of patients presenting with cerebrovascular accident and coma was 23.8% and 0% after medical management versus 67.1% and 57.1% after surgery (log rank, P < .001), respectively. CONCLUSIONS:Brain injury at presentation adversely affects hospital survival of patients with type A acute aortic dissection. In the present observational study, the patients selected to undergo surgery demonstrated improved late survival and frequent reversal of neurologic deficits.

Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ε-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor-mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures.

OBJECTIVES/OBJECTIVE:This study sought to evaluate the long-term outcomes after transcatheter aortic valve implantation (TAVI) in the Multicenter Canadian Experience study, with special focus on the causes and predictors of late mortality and valve durability. BACKGROUND:Very few data exist on the long-term outcomes associated with TAVI. METHODS:This was a multicenter study including 339 patients considered to be nonoperable or at very high surgical risk (mean age: 81 ± 8 years; Society of Thoracic Surgeons score: 9.8 ± 6.4%) who underwent TAVI with a balloon-expandable Edwards valve (transfemoral: 48%, transapical: 52%). Follow-up was available in 99% of the patients, and serial echocardiographic exams were evaluated in a central echocardiography core laboratory. RESULTS:At a mean follow-up of 42 ± 15 months 188 patients (55.5%) had died. The causes of late death (152 patients) were noncardiac (59.2%), cardiac (23.0%), and unknown (17.8%). The predictors of late mortality were chronic obstructive pulmonary disease (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 1.53 to 3.11), chronic kidney disease (HR: 1.08 for each decrease of 10 ml/min in estimated glomerular filtration rate, 95% CI: 1.01 to 1.19), chronic atrial fibrillation (HR: 1.44, 95% CI: 1.02 to 2.03), and frailty (HR: 1.52, 95% CI: 1.07 to 2.17). A mild nonclinically significant decrease in valve area occurred at 2-year follow-up (p < 0.01), but no further reduction in valve area was observed up to 4-year follow-up. No changes in residual aortic regurgitation and no cases of structural valve failure were observed during the follow-up period. CONCLUSIONS:Approximately one-half of the patients who underwent TAVI because of a high or prohibitive surgical risk profile had died at a mean follow-up of 3.5 years. Late mortality was due to noncardiac comorbidities in more than one-half of patients. No clinically significant deterioration in valve function was observed throughout the follow-up period.

BACKGROUND:A considerable number of patients with acute type B aortic dissection (ABAD) treated with medical management alone will exhibit aortic enlargement during follow-up, which could lead to aortic aneurysm and rupture. The purpose of this study was to investigate predictors of aortic expansion among ABAD patients enrolled in the International Registry of Acute Aortic Dissection. METHODS:We analyzed 191 ABAD patients treated with medical therapy alone enrolled in the registry between 1996 and 2010, with available descending aortic diameter measurements at admission and during follow-up. The annual aortic expansion rate was calculated for all patients, and multivariate regression analysis was used to investigate factors affecting the expansion rate. RESULTS:Aortic expansion was observed in 59% of ABAD patients; mean expansion rate was 1.7±7 mm/y. In multivariate analysis, white race (regression coefficient [RC], 4.6; 95% confidence interval [CI], 1.4 to 7.7) and an initial aortic diameter less than 4.0 cm (RC, 6.3; 95% CI, 4.0 to 8.6) were associated with increased aortic expansion. Female sex (RC, -3.8; 95% CI, -6.1 to -1.4), intramural hematoma (RC, -3.8; 95% CI, -6.5 to -1.1), and use of calcium-channel blockers (RC, -3.8; 95% CI, -6.2 to -1.3) were associated with decreased aortic expansion. CONCLUSIONS:White race and a small initial aortic diameter were associated with increased aortic expansion during follow-up, and decreased aortic expansion was observed among women, patients with intramural hematoma, and those on calcium-channel blockers. These data raise the possibility that the use of calcium-channel blockers after ABAD may reduce the rate of aortic expansion, and therefore further investigation is warranted.

BACKGROUND:Acute aortic intramural hematoma (IMH) is an important subgroup of aortic dissection, and controversy surrounds appropriate management. METHODS AND RESULTS/RESULTS:Patients with acute aortic syndromes in the International Registry of Acute Aortic Dissection (1996-2011) were evaluated to examine differences between patients (based on the initial imaging test) with IMH or classic dissection (AD). Of 2830 patients, 178 had IMH (64 type A [42%], 90 type B [58%], and 24 arch). Patients with IMH were older and presented with similar symptoms, such as severe pain. Patients with type A IMH were less likely to present with aortic regurgitation or pulse deficits and were more likely to have periaortic hematoma and pericardial effusion. Although type A IMH and AD were managed medically infrequently, type B IMH were more frequently treated medically. Overall in-hospital mortality was not statistically different for type A IMH compared to AD (26.6% versus 26.5%; P=0.998); type A IMH managed medically had significant mortality (40.0%), although less than classic AD (61.8%; P=0.195). Patients with type B IMH had a hospital mortality that was less but did not differ significantly (4.4% versus 11.1%; P=0.062) from classic AD. One-year mortality was not significantly different between AD and IMH. CONCLUSIONS:Acute IMH has similar presentation to classic AD but is more frequently complicated with pericardial effusions and periaortic hematoma. Patients with IMH have a mortality that does not differ statistically from those with classic AD. A small subgroup of type A IMH patients are managed medically and have a significant in-hospital mortality.

OBJECTIVE:Bone morphogenetic protein-2 (BMP-2) is a major regulator of aortic valve calcification. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression and miRNA-141 is a known repressor of BMP-2-mediated osteogenesis. We hypothesized that miRNA-141 is a key regulator of aortic valve calcification. METHODS:Porcine valvular interstitial cells were isolated, transfected with miRNA-141 or control, and stimulated with transforming growth factor-β. The BMP-2, extracellular signal-regulated kinase 1/2, and runt-related transcription factor 2 levels were determined by immunoblotting and reverse transcriptase polymerase chain reaction. To determine the role of miRNA-141 in bicuspid aortic valve disease, human bicuspid (n = 19) and tricuspid (n = 17) aortic valve leaflets obtained intraoperatively were submitted for GenoExplorer human microRNA array, immunoblotting, and histologic and immunohistochemical analyses. RESULTS:Stimulation of porcine aortic valvular interstitial cells with transforming growth factor-β induced morphologic alterations consistent with myofibroblastic transformation, BMP-2 signaling, and calcification. Transfection with miRNA-141 restored transforming growth factor-β-induced valvular interstitial cell activation, BMP-2 signaling, and alkaline phosphatase activity (3.55 ± 0.18 vs 4.01 ± 0.21, P < .05), suggesting upstream regulation by miRNA-141. miRNA microarray demonstrated differential expression of 35 of 1583 miRNA sequences in the bicuspid versus tricuspid aortic valve leaflets, with a 14.5-fold decrease in miRNA-141 in the bicuspid versus tricuspid leaflets (P < .05). This was associated with significantly increased BMP-2 protein expression in bicuspid aortic valve compared with the tricuspid aortic valve leaflets (P < .001). CONCLUSIONS:We report a completely novel role of miRNA-141 as a regulator of BMP-2-dependent aortic valvular calcification and demonstrate marked attenuation of miRNA-141 expression in patients with bicuspid aortic valve-associated aortic stenosis. Therapeutic targeting of miRNA-141 could serve as a novel strategy to limit progressive calcification in aortic stenosis.

The effects of medications on the outcome of aortic dissection remain poorly understood. We sought to address this by analyzing the International Registry of Acute Aortic Dissection (IRAD) global registry database. A total of 1,301 patients with acute aortic dissection (722 with type A and 579 with type B) with information on their medications at discharge and followed for ≤5 years were analyzed for the effects of the medications on mortality. The initial univariate analysis showed that use of β blockers was associated with improved survival in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in patients with type A who received surgery (p = 0.006). The analysis also showed that use of calcium channel blockers was associated with improved survival in patients with type B overall (p = 0.02) and in patients with type B receiving medical management (p = 0.03). Multivariate models also showed that the use of β blockers was associated with improved survival in those with type A undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p = 0.02) and the use of calcium channel blockers was associated with improved survival in patients with type B medically treated patients (odds ratio 0.55, 95% confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study showed that use of β blockers was associated with improved outcome in all patients and in type A patients (overall as well as in those managed surgically). In contrast, use of calcium channel blockers was associated with improved survival selectively in those with type B (overall and in those treated medically). The use of angiotensin-converting enzyme inhibitors did not show association with mortality.

OBJECTIVES/OBJECTIVE:The aim of this study was: 1) to evaluate the acute and late outcomes of a transcatheter aortic valve implantation (TAVI) program including both the transfemoral (TF) and transapical (TA) approaches; and 2) to determine the results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty. BACKGROUND:Very few data exist on the results of a comprehensive TAVI program including both TA and TF approaches for the treatment of severe aortic stenosis in patients at very high or prohibitive surgical risk. METHODS:Consecutive patients who underwent TAVI with the Edwards valve (Edwards Lifesciences, Inc., Irvine, California) between January 2005 and June 2009 in 6 Canadian centers were included. RESULTS:A total of 345 procedures (TF: 168, TA: 177) were performed in 339 patients. The predicted surgical mortality (Society of Thoracic Surgeons risk score) was 9.8 +/- 6.4%. The procedural success rate was 93.3%, and 30-day mortality was 10.4% (TF: 9.5%, TA: 11.3%). After a median follow-up of 8 months (25th to 75th interquartile range: 3 to 14 months) the mortality rate was 22.1%. The predictors of cumulative late mortality were peri-procedural sepsis (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.48 to 8.28) or need for hemodynamic support (HR: 2.58, 95% CI: 1.11 to 6), pulmonary hypertension (PH) (HR: 1.88, 95% CI: 1.17 to 3), chronic kidney disease (CKD) (HR: 2.30, 95% CI: 1.38 to 3.84), and chronic obstructive pulmonary disease (COPD) (HR: 1.75, 95% CI: 1.09 to 2.83). Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population, and porcelain aorta patients tended to have a better survival rate at 1-year follow-up. CONCLUSIONS:A TAVI program including both TF and TA approaches was associated with comparable mortality as predicted by surgical risk calculators for the treatment of patients at very high or prohibitive surgical risk, including porcelain aorta and frail patients. Baseline (PH, COPD, CKD) and peri-procedural (hemodynamic support, sepsis) factors but not the approach determined worse outcomes.