Recombinant activated factor VII for hemostasis in patients undergoing complex ascending aortic surgery: A single-center, single-surgeon retrospective analysis.

BACKGROUND: Use of recombinant activated factor VII (rFVIIa) to achieve hemostasis during cardiac surgery continues to be debated, as support for its efficacy and safety has not been consistent. We examined our experience with rFVIIa for achieving hemostasis in high-risk patients undergoing complex ascending aortic surgery. METHODS: We reviewed patients who underwent complex ascending aortic surgery performed by a single surgeon (C. K. R.) from August 2014 to February 2019. Outcomes of patients who received rFVIIa were compared with those who did not. RESULTS: Of 59 consecutive patients, 20 patients (33.9%) received rFVIIa, whereas 39 (66.1%) did not. Median dose was 45.4 mcg/kg. rFVIIa was administered intraoperatively to 95% of patients who received it. Most patients underwent combined aortic valve, ascending aorta, and aortic arch surgery (80.0% vs. 64.1%, p = .52). Patients receiving rFVIIa had longer mean cross clamp times (212 vs. 173 min, p = .03) and received a greater median number of intraoperative blood products (18.5 vs. 12.0, p < .001). The number of patients who needed postoperative products (75.0% vs. 60.5%, p = .39), the median number of blood products transfused postoperatively (2 vs. 2, p = .40), and chest tube output (1138 vs. 805 ml, p = .17) were similar between groups. In-hospital mortality was similar between groups (10.0% vs. 10.3%, p = 1.00). Incidences of postoperative stroke (10.0% vs. 13.5%, p = 1.00) and thromboembolic events (10.0% vs. 13.5%, p = 1.00) were similar. CONCLUSIONS: Administration of rFVIIa intraoperatively for refractory bleeding during complex ascending aortic surgery provided hemostasis without greater in-hospital mortality or a higher risk of stroke and thromboembolic events.

Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation.

RATIONALE: Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species. Flow-mediated dilation in patients with cardiovascular disease is dependent on the formation of reactive oxygen species. OBJECTIVE: We examined the hypothesis that telomerase activity modulates microvascular flow-mediated dilation, and loss of telomerase activity contributes to the change of mediator from nitric oxide to mitochondrial hydrogen peroxide in patients with coronary artery disease (CAD). METHODS AND RESULTS: Human coronary and adipose arterioles were isolated for videomicroscopy. Flow-mediated dilation was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a 2-way analysis of variance repeated measure (n≥4; P<0.05). L-NAME (N(ω)-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor) abolished flow-mediated dilation in arterioles from subjects without CAD, whereas polyethylene glycol-catalase (PEG-catalase; hydrogen peroxide scavenger) had no effect. After exposure to BIBR-1532, arterioles from non-CAD subjects maintained the magnitude of dilation but changed the mediator from nitric oxide to mitochondrial hydrogen peroxide (% max diameter at 100 cm H2O: vehicle 74.6±4.1, L-NAME 37.0±2.0*, PEG-catalase 82.1±2.8; BIBR-1532 69.9±4.0, L-NAME 84.7±2.2, PEG-catalase 36.5±6.9*). Conversely, treatment of microvessels from CAD patients with the telomerase activator AGS 499 converted the PEG-catalase-inhibitable dilation to one mediated by nitric oxide (% max diameter at 100 cm H2O: adipose, AGS 499 78.5±3.9; L-NAME 10.9±17.5*; PEG-catalase 79.2±4.9). Endothelial-independent dilation was not altered with either treatment. CONCLUSIONS: We have identified a novel role for telomerase in re-establishing a physiological mechanism of vasodilation in arterioles from subjects with CAD. These findings suggest a new target for reducing the oxidative milieu in the microvasculature of patients with CAD.

Surgical thoracic sympathectomy induces structural and biomechanical remodeling of the thoracic aorta in a porcine model.

BACKGROUND: Sympathetic innervation exerts marked effects on vascular smooth muscle cells, including a short-term homeostatic (vasoconstrictor) and a direct trophic action promoting differentiation. However, the role of sympathetic nervous system in long-term structural and functional modulation of the aortic wall is yet undefined. METHODS: Six Landrace pigs underwent bilateral thoracic sympathectomy from the stellate to T8 ganglion, whereas 10 pigs underwent sham operation. Animals were sacrificed 3 mo postoperatively. Histometrical examination was performed on specimens from the thoracic (TA) and abdominal aorta (AA) utilizing an image-processing system. A uniaxial tensile tester was utilized for biomechanical evaluation; parameters of extensibility, strength, and stiffness of aortic tissue were calculated. RESULTS: Structural aortic remodeling of sympathectomized animals was observed, including increased inner aortic diameter in TA (15.3 ± 0.4 versus 10.4 ± 0.2 mm, P < 0.001) and AA (6.7 ± 0.3 versus 5.3 ± 0.2 mm, P = 0.002), and increased wall thickness in TA (2.0 ± 0.1 versus 1.6 ± 0.1 mm, P < 0.001) but not AA. Microscopic image analysis revealed increased elastin (TA: 50.1 ± 1.1 versus 29.7% ± 0.6%, P < 0.001; AA: 20.4 ± 2.1 versus 16.3% ± 0.6%, P = 0.03) and collagen density (only in TA: 22.0 ± 0.9 versus 15.4% ± 0.5%, P < 0.001), and decreased smooth muscle density (TA: 27.6 ± 1.3 versus 54.9% ± 0.7%, P < 0.001; AA: 57.2 ± 1.5 versus 63.4% ± 0.8%, P < 0.001). Sophisticated biomechanical analysis demonstrated that following sympathectomy, TA was equally extensible but manifested augmented strength (1344 ± 73 versus 1071 ± 52 kPa, P = 0.004) and stiffness (6738 ± 478 versus 5026 ± 273 kPa, P = 0.003), in accordance with extracellular matrix protein accumulation in that region. Differences in the AA were non-significant. CONCLUSIONS: Chronic thoracic sympathetic denervation causes significant structural and biomechanical remodeling of the thoracic aorta. Possible clinical implications for patients undergoing thoracic sympathectomy or chronically treated with sympathetic blockers require further investigation.

Treatment with simvastatin inhibits the formation of abdominal aortic aneurysms in rabbits.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a common and lethal disease. AAAs are associated with atherosclerosis, chronic inflammation, and extracellular matrix degradation. The aim of this study was to determine whether treatment with simvastatin can influence the development of experimental aortic aneurysms in a rabbit model. MATERIALS AND METHODS: A total of 76 rabbits were randomized in four groups: in group I (n = 12), where the abdominal aortas were exposed to 0.9% NaCl, and in group II (n = 24), group III (n = 24) and group IV (n = 18), where the aortas were exposed to CaCl2 0.5 mol/L for 15 minutes after laparotomy. Group III received 2 mg/kg simvastatin daily starting 7 days before laparotomy, and in group IV, the daily treatment with simvastatin started 7 days after laparotomy. Animals were sacrificed at intervals of first, second, third, and fourth week to obtain measurements of aortic diameter and histological examination. Moreover, immunohistochemistry was used in order to examine the relative distribution of matrix metalloproteinases (MMPs) 2 and 9 (MMP-2 and MMP-9, respectively) and tissue inhibitor 1 of MMPs within the aortic aneurysms. RESULTS: The increase of aortic diameter in animals of group I ranged from 4.6% to 7.6%; in group II, from 41% to 85% (P < 0.001 vs. group I); in group III, from 9% to 18% (group II vs. group III, P < 0.001); and in group IV; from 36% to 38%. Moreover, aortic specimens of group II presented a statistically significant increase in MMP-2 and MMP-9 immunoexpression compared with other groups (I, III, IV) (P < 0.05 for all comparisons), with the exception of animals of group IV at the end of second week. Immunoreactivity of tissue inhibitor 1 of MMPs was not statistically different among groups II, III, and IV. CONCLUSIONS: Simvastatin may prove clinically significant in suppressing the development and expansion of AAAs and, thereby, in reducing the risk of rupture and the need for repair.

Rare and complicated functional posterior mediastinal paraganglioma.

Functional mediastinal paragangliomas (PGs) are rare, catecholamine-secreting tumours. Surgical resection is the preferred treatment, but it can be complicated by catecholamine-related symptoms, involvement of cardiac structures and/or tumour supply from major blood vessels. We report a case of a man in his 30s with a subcarinal functional PG complicated by all three factors. The PG had arterial supplies from the right coronary and bronchial arteries, with mass effect on the left atrium. Given the high risk of intraoperative bleeding, catecholamine surges and injury to right coronary artery, we attempted a minimally invasive strategy that incorporates best practices from the few published cases on functional PGs. We show that a multidisciplinary approach involving alpha/beta blockade, preoperative embolisation of tumour blood supply, robotic-assisted tumour mobilisation and, if needed, open resection with cardiopulmonary bypass can be a safe strategy in the treatment of functional mediastinal paragangliomas adherent to cardiac structures.

Calcified Homograft With Aortic Insufficiency: A Hybrid Alternative Approach to Clamping.

Surgical management of a calcified homograft with associated severe aortic insufficiency is challenging because of the technical difficulty in occluding the aorta. We present a hybrid method of homograft occlusion during the cooling phase of a homograft replacement procedure that required the use of circulatory arrest.

Primary Lymphoma Presenting in an Ascending Aortic Aneurysm: A Case Report.

Small lymphocytic lymphoma (SLL) is rarely associated with thoracic aortic aneurysms. Aneurysm of the ascending aorta associated with SLL has never been reported before. We describe the case of an asymptomatic 68-year-old woman who presented with a 5.5-cm aneurysm of the ascending aorta and no prior history of hematological disorders. Following excision and repair, the surgical specimen showed infiltration of the aortic wall by lymphocytes, expressing markers consistent with SLL. While symptomatic SLL carries a poor prognosis, risk stratification tools are applied to guide management strategies in asymptomatic patients.

Performing modified fontan before six years of age leads to superior long-term exercise capacity.

We investigated the influence of age at Fontan completion on the exercise capacity of patients who underwent a Fontan operation. Our study demonstrated that age at the time of the Fontan operation significantly affects the peak oxygen consumption at mid-term follow up and that exercise capacity is superior in patients who have undergone Fontan completion at an earlier age. These findings provide support for recommendations to perform Fontan completion procedures relatively early.

Impact of early and delayed stroke on in-hospital and long-term mortality after isolated coronary artery bypass grafting.

Stroke after coronary artery bypass grafting (CABG) is an infrequent, yet devastating complication with increased morbidity and mortality. We sought to determine risk factors for early (intraoperatively to 24 hours) and delayed (>24 hours to discharge) stroke and to identify their impact on long-term mortality after CABG. We studied 4,140 consecutive patients who underwent isolated CABG from 1992 to 2003. Long-term survival data (mean follow-up 7.4 years) were obtained from the National Death Index. Independent predictors for stroke and in-hospital mortality were determined by multivariate logistic regression analysis including all available preoperative, intraoperative, and postoperative risk factors. Independent predictors for long-term mortality were determined by multivariate Cox regression analysis. One hundred two patients (2.5%) developed early stroke and 36 patients (0.9%) delayed stroke. Independent predictors for early stroke were age, recent myocardial infarction, smoking, femoral vascular disease, body mass index, reoperation for bleeding, postoperative sepsis and/or endocarditis, and respiratory failure, whereas those for delayed stroke were female gender, white race, preoperative renal failure, respiratory failure, and postoperative renal failure. Early stroke was an independent predictor for in-hospital (odds ratio 3.49, 95% confidence interval [CI] 1.56 to 7.80, p = 0.002) and long-term (hazard ratio 1.70, 95% CI 1.30 to 2.21, p <0.001) mortalities. Delayed stroke was not an independent predictor for in-hospital (odds ratio 0.90, 95% CI 0.23 to 3.51, p = 0.878) or long-term (hazard ratio 0.66, 95% CI 0.38 to 1.17, p = 0.156) mortality. In conclusion, risk factors for early in-hospital stroke differ from those of delayed in-hospital stroke after CABG. Early stroke is an independent predictor for in-hospital and long-term mortalities, suggesting the need for a more frequent follow-up and appropriate pharmacologic therapy after discharge.

Independent predictors for early and long-term mortality after heart valve surgery.

BACKGROUND AND AIM OF THE STUDY: Patients with heart valve surgery may have a periprocedural mortality extending up to one year after surgery. The study aim was to determine independent predictors for in-hospital and long-term mortality after heart valve surgery. METHODS: A total of 1,376 consecutive patients who underwent isolated or combined heart valve surgery at a single institution was studied. Multivariate logistic regression analysis was used to determine independent predictors for in-hospital mortality. Long-term survival data (mean follow up 5.6 years) were obtained from the National Death Index. Multivariate Cox regression analysis was used to determine independent predictors for long-term mortality. All available preoperative, intraoperative and postoperative risk factors were included in these analyses. RESULTS: The mean EuroSCORE was 6.2 +/- 3.7. There were 86 (6.3%) in-hospital and 550 (40.0%) late deaths. Eleven independent predictors were determined for in-hospital mortality, and 13 for long-term mortality. There were six common independent predictors (preoperative dialysis, total bypass time, intraoperative stroke, postoperative sepsis and/or endocarditis, renal and respiratory failure). Unique independent predictors for in-hospital mortality included intra-aortic balloon pump, preoperative endocarditis, intravenous use of nitroglycerine, bleeding requiring reoperation and gastrointestinal complications. The model for in-hospital mortality showed acceptable calibration (Lemeshow-Hosmer, p = 0.629) and excellent discriminatory ability (C statistic 0.88). Unique independent predictors for long-term mortality included age, ejection fraction, stroke prior to surgery, hemodynamic instability, chronic obstructive pulmonary disease and deep sternal wound infection. CONCLUSION: Independent predictors were determined for early and long-term mortality after heart valve surgery. The prevention of postoperative complications may be a key element for increased early and long-term survival in these patients.

Migration of endovascular plug in hybrid repair of dysphagia lusoria.

Aberrant right subclavian artery is the most common brachiocephalic artery congenital abnormality and may result in dysphagia from external compression by the aberrant artery on the esophagus. Repair of this anatomic variant can be performed by both open and hybrid endovascular techniques. This case illustrates a complication of a hybrid repair resulting in proximal migration of a vascular occlusion plug, presenting as recurrent dysphagia and need for open surgical extraction of the plug.

Aortic coarctation in the adult: management of complications and coexisting arterial abnormalities with hypothermic cardiopulmonary bypass and circulatory arrest.

OBJECTIVES: Adult patients with aortic coarctation may have complications after childhood repair. Other adult patients have coarctation and aneurysms of the aorta and the left subclavian artery. The optimal management of such cases is not clearly established. We evaluated the role of hypothermic cardiopulmonary bypass and circulatory arrest. METHODS: Thirteen adult patients (mean age 38 years) with coarctation and coexisting abnormalities of the aorta and left subclavian artery were treated. Five patients had pseudoaneurysms develop after bypass grafting (n = 3) or patch angioplasty (n = 2). These were detected a mean of 21 years (range 13-44 years) after the initial operation. Four pseudoaneurysms were asymptomatic, and 1 had ruptured. One patient had recurrent coarctation from fibrous obliteration of a 10-mm bypass graft inserted 15 years previously. The remaining 7 patients had aneurysms of the left subclavian artery (n = 5), aneurysms of the ascending aorta and arch (n = 1), or stenosis of the left subclavian artery (n = 1) in combination with moderate or severe coarctation. Resection and interposition graft replacement of the aneurysmal or stenotic aortic segments were performed in all cases with an interval of hypothermic circulatory arrest that averaged 44 +/- 5 minutes (range 33-54 minutes). Seven patients had interposition graft replacement of aneurysmal or stenotic left subclavian arteries. RESULTS: There were no in-hospital or late deaths (maximal follow-up 7 years). No patient had brain injury, paralysis, myocardial, respiratory, or renal failure. No patient has evidence of recurrent coarctation or aneurysm formation. CONCLUSIONS: Cardiopulmonary bypass with hypothermic circulatory arrest can safely be used in the treatment of complex adult coarctation. It permits accurate delineation of the anatomy with minimal dissection, avoidance of aortic clamping and sacrifice of intercostal arteries, precise interposition graft repair, and adequate protection of vital organs.

Single-stage reoperative repair of chronic type A aortic dissection using the arch-first technique.

BACKGROUND: Management of the enlarged, chronically dissected aorta after previous repair of acute ascending aortic dissection or after a previous cardiac operation may present a formidable technical challenge and the optimal method of management is not clearly established. METHODS: Twenty-one patients with chronic type A aortic dissection (mean age 57 years) underwent resection of the ascending aorta, the aortic arch, and varying segments of the descending thoracic aorta. Single-stage replacement with perfusion of the aortic arch first to minimize the duration of brain ischemia and a bilateral anterior thoracotomy (clamshell) incision were used. Fourteen patients had undergone previous repair of acute type A dissection. Seven patients had type A dissection after aortic valve replacement (3 patients) or coronary artery bypass (4 patients). Marked enlargement of the aorta distal to the left subclavian artery precluded a two-stage repair. The mean interval between the initial and reoperative procedures was 69 months (range, 5 to 249). RESULTS: There was 1 (4.8%) hospital death. Four patients required reoperation for bleeding. One patient required a right ventricular assist device that was successfully removed. Ten patients required assisted ventilation for more than 48 hours. All were successfully weaned from ventilatory support. No patient had a stroke or other adverse neurologic outcome. There has been 1 late death (mean follow-up 2 years). CONCLUSIONS: The single-stage, arch-first replacement technique is a safe and effective procedure for patients who require extensive reoperations for chronic expanding type A dissection.

Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with circulatory arrest is an important adjunct for operations on the distal aortic arch, the descending thoracic, and the thoracoabdominal aorta. The safety and efficacy of this technique when compared with other adjuncts (ie, simple aortic clamping, partial cardiopulmonary bypass, regional hypothermia) is not clearly established. METHODS: One hundred and ninety-two patients (age range, 20 to 83 years) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the involved aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest (mean, 38 minutes). The technique was used when the location and severity of disease precluded placement of clamps on the proximal aorta (31 patients) or (in 161 patients) when extensive thoracic (47) or thoracoabdominal (114) aortic disease was present, and the risk for development of spinal cord ischemic injury was judged to be increased. Lower intercostal and lumbar arteries were attached separately to the aortic graft in 101 of the 161 patients (63%) who had extensive aortic replacement. No other adjuncts for spinal cord protection were used. RESULTS: The 30-day mortality was 6.8% (13 patients). It was 40% (8 of 20) for patients having emergent operations (acute aortic dissection or rupture) and 2.9% (5 of 172) for all others (p < 0.001). The 90-day mortality was 12.5% (24 patients). Paraplegia occurred in 4 and paraparesis in 1 (full recovery) of the 186 operative survivors whose lower limb function could be assessed postoperatively (2.7%). Among the 109 survivors with thoracoabdominal aortic disease, early paraplegia occurred in 1 of 36 with Crawford extent I, 0 of 42 with extent II, and 2 of 31 with extent III disease. One patient (extent II) developed paraplegia on the 9th postoperative day after a hypotensive episode. None of the 47 patients with aortic dissection developed paralysis. Among the 186 operative survivors, renal dialysis was required in 4 patients (2.2%), prolonged inotropic support in 18 (10%), reoperation for bleeding in 9 (5%), mechanical ventilation (> or = 48 hours) in 64 (34%), and tracheostomy in 17 (9%). Four patients (2%) sustained a stroke. CONCLUSIONS: Hypothermic cardiopulmonary bypass with circulatory arrest provides safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure that equals or exceeds that of other currently used techniques but without the need of other adjuncts.

Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia.

BACKGROUND: Potassium adenosine triphosphate (KATP) channel openers have been involved in the enhancement of ischemic tolerance in various tissues. The purpose of the present study is to evaluate the effects of aprikalim, a specific KATP channel opener, on spinal cord ischemic injury. METHODS: Fifty-four rabbits were randomly assigned to three groups: group 1 (n = 18, sham operation), group 2 (n = 18, 30 min of normothermic aortic cross-clamping) and group 3 (n = 18, aprikalim 100 µg/kg was administered 15 min before 30 min of normothermic aortic cross-clamping). Neurologic evaluation was performed according to the modified Tarlov scale. Six animals from each group were sacrificed at 24, 48 and 168 h postoperatively. The lumbar spinal cords were harvested and examined histologically. The motor neurons were counted and the histologic lesions were scored (0-3, 3: normal). RESULTS: Group 3 (aprikalim group) had better Tarlov scores compared to group 2 at all-time points (P < 0.025). The histologic changes were proportional to the Tarlov scores and group 3 had better functional outcome as compared to group 2 at 168 h (number of neurons: 21.2 ± 4.9 vs. 8.0 ± 2.7, P < 0.001 and histologic score: 1.67 ± 1.03 vs. 0.50 ± 0.55, P = 0.03). Although aprikalim exhibited improved effect on clinical and histologic neurologic outcome when compared to normothermic spinal cord ischemia, animals in group 3 had worse Tarlov score, reduced number of motor neurons and worse histologic score when compared to group 1 (sham operation) at 168 h (P = 0.003, P = 0.001 and P = 0.019 respectively). CONCLUSION: Aprikalim reduces the severity of spinal cord ischemic injury in a rabbit model of spinal cord ischemia.