Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease

In 2014, the Canadian Cardiovascular Society (CCS) published a position statement on the management of thoracic aortic disease addressing size thresholds for surgery, imaging modalities, medical therapy, and genetics. It did not address issues related to surgical intervention. This joint Position Statement on behalf of the CCS, Canadian Society of Cardiac Surgeons, and the Canadian Society for Vascular Surgery provides recommendations about thoracic aortic disease interventions, including: aortic valve repair, perfusion strategies for arch repair, extended arch hybrid reconstruction for acute type A dissection, endovascular management of arch and descending aortic aneurysms, and type B dissection. The position statement is constructed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and has been approved by the primary panel, an international secondary panel, and the CCS Guidelines Committee. Advent of endovascular technology has improved aortic surgery safety and extended the indications of minimally invasive thoracic aortic surgery. The combination of safer open surgery with endovascular treatment has improved patient outcomes in this rapidly evolving subspecialty field of cardiovascular surgery.

Esophageal aperistalsis following fundoplication in a patient with trisomy 21.

Gastrointestinal abnormalities are frequent in patients with Down syndrome (DS), gastroesophageal reflux (GER) being prominent among them. A 10-year-old boy with DS presented with progressive daily vomiting and an upper gastrointestinal study documenting reflux. A laparoscopic Nissen fundoplication was performed uneventfully. Postoperative inability to take solids was noted and a contrast study showed a tight gastroesophageal junction and poor peristalsis. Persistent symptoms were not alleviated by esophageal dilatation, despite a relaxing lower esophageal sphincter. Esophageal manometry documented complete esophageal aperistalsis. A percutaneous endoscopic gastrostomy was placed and the patient required long-term tube feeds. Esophageal aperistalsis is a rare condition in DS, likely superimposed on GER. Fundoplication may adversely affect the already abnormal esophageal motility in these children. Esophageal manometry preoperatively will identify motility disorders and assist in selecting the best management for these patients.

Multiple arterial grafts. Radial versus right internal thoracic arteries.

BACKGROUND: Left internal thoracic artery (LITA) grafts to the left anterior descending coronary artery (LAD) during coronary bypass surgery (CABG) have greater patency rates than saphenous vein grafts and reduce long-term cardiac morbidity and mortality rates. The benefits of multiple versus single arterial grafts and the role of different arterial conduits with respect to short- and medium-term outcome remains controversial. The purpose of this study was to compare the perioperative and intermediate-term results of: (1) patients receiving 2 arterial grafts versus 1 arterial graft and (2) patients receiving a right internal thoracic artery (RITA) versus a radial artery (RA) as the second arterial graft. METHODS AND RESULTS: Retrospective analysis of prospectively gathered data on consecutive patients undergoing isolated CABG at our institution between 1989 and 1996 was conducted. The first section of the study compared outcomes for 1 arterial graft (LITA to LAD, n = 2333) versus 2 arterial grafts (LITA + RA or LITA + RITA, n = 378). The second section of the study compared outcomes for the RITA (n = 132) versus the RA (n = 171) as second arterial grafts since 1992, when the radial series was initiated. Part I: By multivariable stepwise logistic regression, the use of 1 arterial graft was associated with an increased incidence of perioperative cardiac morbidity and mortality (odds ratio 2.2, 95% confidence interval 1.4 to 3.3), with the use of our current patient selection criteria. Double-arterial graft patients had a nonsignificant trend toward increased intermediate-term actuarial survival (P = 0.12) and cardiac event-free survival (P = 0.09). Part II: Comparison of preoperative demographics revealed a higher incidence of diabetes (27% vs 11%, P < 0.001), peripheral vascular disease (16% vs 8%, P = 0.03), and elderly age (13% vs 2%, P = 0.001) in patients receiving an RA versus those receiving a RITA as the second arterial graft. Perioperative outcome analysis revealed a decreased intensive care unit stay in the RA versus RITA group (median 30.4 vs 36.2 hours, respectively, P = 0.005) but no significant difference in hospital length of stay. There was no significant difference in perioperative mortality or cardiac morbidity rates. RITA patients had a higher incidence of sternal wound infection (5.3% vs 0.6%, P = 0.01), however, and tended to have increased blood product transfusion rates (51% vs 40%, P = 0.06). CONCLUSIONS: The use of 2 arterial grafts is safe, with a reduction in perioperative cardiac morbidity or mortality rates compared with 1 arterial graft after adjustment for other risk variables. When comparing RITA to RA as second arterial grafts, patients receiving an RA have a lower incidence of sternal wound infection and decreased transfusion requirements, with no difference in perioperative or intermediate-term cardiac morbidity or mortality rates.

Phase 2 studies of adenosine cardioplegia.

BACKGROUND: Laboratory evidence supports the use of adenosine-supplemented cardioplegia. An initial phase 1 dose-ranging clinical evaluation demonstrated that an adenosine concentration of 15 mumol/L could be safely administered with warm blood cardioplegia and suggested that phase 2 studies were warranted. METHODS AND RESULTS: Two separate double-blind, randomized, placebo-controlled trials were performed in patients undergoing primary, isolated, nonemergent coronary artery bypass graft surgery. Patients were randomized to receive adenosine 15 mumol/L versus placebo in the first study (n = 200) and adenosine 50 or 100 mumol/L versus placebo in the second study (n = 128). Adenosine was infused with both initial and final doses of warm antegrade blood cardioplegia. The data from the 2 trials were combined using the methods of Mantel and Haenszel, and the results of the meta-analysis are presented as the relative risk with their associated 95% confidence intervals (CI). The different study groups were comparable with respect to all preoperative clinical characteristics, angiographic findings, and intraoperative variables. In both trials 1 and 2, no differences were found between groups in the incidence of the individual primary or secondary outcomes. Similarly, when both studies were combined, there was no significant evidence of any consistent treatment benefit (primary: death: relative risk [RR] = 1.02, 95% CI = 0.06, 16.6; myocardial infarction by CK-MB: RR = 0.84, CI = 0.54, 1.31; low output syndrome: RR = 1.38, CI = 0.29, 6.42; any of the above: RR = 0.98, CI = 0.78, 1.25; secondary: Q-wave myocardial infarction: RR = 1.30, CI = 0.41, 4.13; myocardial infarction by troponin T: RR = 0.7, CI = 0.40, 1.21; inotrope requirement: RR = 0.9, CI = 0.46, 1.79; intra-aortic balloon pump requirement: RR = 0.6, CI = 0.07, 4.81; P > 0.20). CONCLUSIONS: Despite promising experimental data, adenosine supplementation of warm blood cardioplegia did not demonstrate any statistically significant benefit in patients undergoing elective coronary artery bypass graft surgery. Although sample sizes were relatively small, based on our interim analyses, it is unlikely that increased patient enrollment would reveal any substantive clinical differences between groups.

Inhibition of the action of nitric oxide prodrugs by pyocyanin: mechanistic studies.

Previously, we reported on the antagonism by pyocyanin (PYO) of the relaxant effects of nitrovasodilators such as glyceryl trinitrate, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1). The purpose of the present study was to elucidate the mechanism of this action of PYO by examining its effect on the steps considered to be necessary for nitrovasodilator-induced relaxation of blood vessels. PYO (10 microM) attenuated the accumulation of guanosine-3',5'-cyclic monophosphate (cGMP) in rabbit aorta induced by nitrovasodilators SIN-1, SNAP, and GTN, 65, 81, and 67%, respectively. Additionally, PYO (1 or 10 microM) interfered with in vitro activation of soluble guanylyl cyclase. PYO did not inhibit vascular relaxation induced by 8-bromo-cyclic guanosine monophosphate. PYO (10 microM) also decreased the quantity of nitric oxide measured in the headspace above intact vascular tissue incubated with glyceryl trinitrate in the presence of oxygen. These observations are consistent with the interpretation that PYO interfered with the nitrovasodilator action of glyceryl trinitrate by inactivation of NO or by inhibition of enzymatic biotransformation of GTN; this would result in decreased guanylyl cyclase activation and thus lowering cellular levels of cGMP. NO chemiluminescence studies with SIN-1 (10 microM) revealed that this NO donor produced NO in a time-dependent manner and PYO (10 microM) caused no inhibition of NO production, but in fact, potentiated NO release after 10 min of incubation (1395 +/- 179 pmol NO compared with 1088 +/- 154 pmol NO). NO production from 10 microM SNAP was similarly potentiated by PYO after 0.5, 2, 5, and 10 min of incubation. Therefore, it is likely that PYO acts as an inhibitor of guanylyl cyclase with respect to NO donors, SIN-1 and SNAP, but it also appears that PYO can exert additional inhibitory effects in the case of vascular relaxation by GTN. Such differences in relaxant effects may reflect inhibition of enzymatic biotransformation that is unique to GTN or that PYO may complex with an alternative redox form of NO (perhaps NO+) that is generated by vascular metabolic activation of GTN.

Inhibition of nitrovasodilators by pyocyanin and methylene blue is dissociated from nitric oxide formation.

The phenazine pigment pyocyanin (Pyo), like methylene blue (MB), inhibits vascular relaxation induced by organic nitrates. These nitrovasodilators are pro-drugs that have in common the ability to generate nitric oxide (NO). In this study, we characterized responses of rabbit isolated aortic ring to 3-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside, glyceryl trinitrate (GTN), and isosorbide dinitrate in the presence and absence of 10 microM Pyo. We also examined the effect of Pyo (1 and 10 microM) and MB (1 and 10 microM) on vasorelaxation induced by authentic NO, and finally we tested the effects of Pyo and MB on the tissue-independent formation of NO from SIN-1, SNAP, and sodium nitroprusside, using the chemiluminescence--headspace gas method. Pyo (10 microM) surmountably inhibited aortic responses to GTN, isosorbide dinitrate, SIN-1, and SNAP with a characteristic rightward shift of the dose-response curve; the apparent EC50 of these drugs for relaxation of phenylephrine-contracted aorta was increased 18-, 4-, 13-, and 15-fold, respectively. Pyo (1 and 10 microM) and MB (10 microM) inhibited NO-induced vasorelaxation at the EC50 of NO by 35, 72, and 56%. In contrast, Pyo did not inhibit sodium nitroprusside induced vasodilation. For a 10-min incubation, 10 microM Pyro or MB increased NO production from SNAP 1.8- and 2.9-fold, respectively, and increased NO production from SIN-1 by 3.8- and 7.1-fold, respectively. Neither Pyo nor MB enhanced NO formation from sodium nitroprusside. These data indicate that Pyo and MB inhibit nitrovasodilator-induced relaxation of aortic ring by interfering with the action of NO, subsequent to its formation.