Multimodality imaging in delineation of complex sinus venosus defects and treatment outcomes over the last decade.

BACKGROUND: Diagnosis of sinus venosus defects, not infrequently associated with complex anomalous pulmonary venous drainage, may be delayed requiring multimodality imaging. METHODS: Retrospective review of all patients from February 2008 to January 2019. RESULTS: Thirty-seven children were diagnosed at a median age of 4.2 years (range 0.5-15.5 years). In 32 of 37 (86%) patients, diagnosis was achieved on transthoracic echocardiography, but five patients (14%) had complex variants (four had high insertion of anomalous vein into the superior caval vein and three had multiple anomalous veins draining to different sites, two of whom had drainage of one vein into the high superior caval vein). In these five patients, the final diagnosis was achieved by multimodality imaging and intra-operative findings. The median age at surgery was 5.2 years (range 1.6-15.8 years). Thirty-one patients underwent double patch repair, four patients a Warden repair, and two patients a single-patch repair. Of the four Warden repairs, two patients had a high insertion of right-sided anomalous pulmonary vein into the superior caval vein, one patient had bilateral superior caval veins, and one patient had right lower pulmonary vein insertion into the right atrium/superior caval vein junction. There was no post-operative mortality, reoperation, residual shunt or pulmonary venous obstruction. One patient developed superior caval vein obstruction and one patient developed atrial flutter. CONCLUSION: Complementary cardiac imaging modalities improve diagnosis of complex sinus venosus defects associated with a wide variation in the pattern of anomalous pulmonary venous connection. Nonetheless, surgical treatment is associated with excellent outcomes.

Pravastatin reduces Marfan aortic dilation.

BACKGROUND: The sequelae of aortic root dilation are the lethal consequences of Marfan syndrome. The root dilation is attributable to an imbalance between deposition of matrix elements and metalloproteinases in the aortic medial layer as a result of excessive transforming growth factor-beta signaling. This study examined the efficacy and mechanism of statins in attenuating aortic root dilation in Marfan syndrome and compared effects to the other main proposed preventative agent, losartan. METHODS AND RESULTS: Marfan mice heterozygous for a mutant allele encoding a cysteine substitution in fibrillin-1 (C1039G) were treated daily from 6 weeks old with pravastatin 0.5 g/L or losartan 0.6 g/L. The end points of aortic root diameter (n=25), aortic thickness, and architecture (n=10), elastin volume (n=5), dp/dtmax (maximal rate of change of pressure) (cardiac catheter; n=20), and ultrastructural analysis with stereology (electron microscopy; n=5) were examined. The aortic root diameters of untreated Marfan mice were significantly increased in comparison to normal mice (0.161 ± 0.001 cm vs 0.252 ± 0.004 cm; P<0.01). Pravastatin (0.22 ± 0.003 cm; P<0.01) and losartan (0.221 ± 0.004 cm; P<0.01) produced a significant reduction in aortic root dilation. Both drugs also preserved elastin volume within the medial layer (pravastatin 0.23 ± 0.02 and losartan 0.29 ± 0.03 vs untreated Marfan 0.19 ± 0.02; P=0.01; normal mice 0.27 ± 0.02). Ultrastructural analysis showed a reduction of rough endoplasmic reticulum in smooth muscle cells with pravastatin (0.022 ± 0.004) and losartan (0.013 ± 0.001) compared to untreated Marfan mice (0.035 ± 0.004; P<0.01). CONCLUSIONS: Statins are similar to losartan in attenuating aortic root dilation in a mouse model of Marfan syndrome. They appear to act through reducing the excessive protein manufacture by vascular smooth muscle cells, which occurs in the Marfan aorta. As a drug that is relatively well-tolerated for long-term use, it may be useful clinically.

Importance of strict patient selection criteria for combined carotid endarterectomy and coronary artery bypass grafting.

BACKGROUND: Management of patients with severe concomitant carotid and coronary disease remains controversial. We report our experience of combined carotid endarterectomy (CEA) and coronary artery bypass surgery (CABG) over a fifteen year period using strict patient selection criteria. METHODS: From 1st January 1995 to December 31st 2009 165 patients underwent combined CABG/CEA procedures at the Mater Hospital. Mean age was 68.2 years (range 43-88) and 127 (77%) were male. Fifty-three (32%) had symptomatic carotid disease. Indications for combined procedures were the presence of symptomatic >70% or asymptomatic >80% internal carotid artery stenosis in a patient requiring urgent CABG because of either unstable angina, recent MI, severe triple vessel disease or severe Left Anterior Descending or Left Main Stem stenosis. RESULTS: Thirty-day stroke and death rate was 3%. All neurological events were in the hemisphere contralateral to the carotid surgery and symptoms had completely resolved prior to discharge from hospital. One patient required evacuation of a cervical haematoma and there were two transient XII nerve palsies. CONCLUSION: Combined CEA/CABG can be performed safely with acceptable morbidity and mortality in patients selected in accordance with strict criteria in a centre with a large experience of both cardiac and carotid surgery.

Intravenous glutamine enhances COX-2 activity giving cardioprotection.

BACKGROUND: Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning. MATERIALS AND METHODS: Male New Zealand white rabbits (n = 28) received either 0.5 g/kg glutamine in 0.9% saline or saline only in divided doses for 3 d. The large marginal branch of the left coronary was occluded for 30 min; cardiac function was assessed during 3 h of reperfusion, and infarct size was measured. 6-Keto-PGF-1alpha, nitrate, and malonaldehyde serum levels were determined. Hearts were taken from a further group of pretreated rabbits (n = 10) to assess myocardial COX-2 and HSP72 levels. RESULTS: Glutamine pretreatment resulted in a 39% reduction in infarct size (30.7 +/- 2.0% versus 50.4 +/- 2.1% controls; P < 0.01). Myocardial COX-2 levels were significantly elevated with pretreatment (P < 0.05) and were mirrored by higher serum 6-keto-PGF-1alpha levels prior to ischemia (69 +/- 13 versus 18 +/- 21 pg/mL in controls, P = 0.027). There was no significant difference in myocardial HSP72 or serum nitrate levels following pretreatment, or malonaldehyde levels during reperfusion. CONCLUSIONS: Glutamine pretreatment confers anti-infarct protection through up-regulation of COX-2, a key mediator of delayed preconditioning protection. Previous confirmation of its clinical safety profile at these doses suggests an acceptable strategy for inducing preconditioning for perioperative protection.

Long-term outcomes following partial atrioventricular septal defect (AVSD) repair in Ireland.

BACKGROUND: We describe the long-term results of partial atrioventricular septal defect (AVSD) repair in a single centre encompassing a 22-year period. Described are rates of survival, reoperation and complications. METHODS: We performed a retrospective review of 556 patients undergoing AVSD repair to identify the 51 patients who underwent partial AVSD repair in Our Lady's Children's Hospital, Crumlin, Ireland, between 1993 and 2015 with long-term follow-up where available. RESULTS: A total of 29 (56.8%) of patients were male and mean age at operation was 3.32 years. Mean weight was 13.2 kg. Trisomy 21 was present in 29 (56.8%). Five patients (9.6%) had undergone prior surgery. Mean cardiopulmonary bypass time was 89 ± 36 min and mean aortic cross-clamp time was 57 ± 28 min. One patient underwent partial AVSD repair and concomitant tracheal resection and extracorporeal membrane oxygenation decannulation. One patient was managed with suture atrial septal defect (ASD) closure, the remainder with patch repair of ASD and mitral cleft closure. The length of hospital stay was 9 ± 5 days. Median follow-up was 6.06 years (IQR, 1.65-10.2 years). There were no early mortalities. One patient died 1 year following surgery (1.9%). One patient required reoperation at an interval of 2 years for severe mitral regurgitation (1.9%). CONCLUSIONS: Short- and long-term survival following partial AVSD repair in Ireland revealed excellent results compared with other published series. Reoperation incidence also compared excellently with other reports published in the literature.

Cardiac valve replacement in human immunodeficiency virus-infected patients.

BACKGROUND: Valve replacement in human immunodeficiency virus (HIV)-infected patients is being performed with increasing frequency, but the early and late results in these immunocompromised patients are not known. METHODS: A 10-year retrospective clinical review was undertaken; patients and their physicians were contacted for follow-up clinical status. RESULTS: Twenty-two HIV-infected patients underwent valve replacement between 1990 and 1999, with no operative or hospital deaths. Mean patient age was 37.6 years; 15 were men. Indications for operation were heart failure in 59% (13/22) and sepsis in 91% (20/22). There were 12 aortic valve replacements, seven mitral valve replacements, and three double valve replacements. Mechanical valves were used in 11, bioprostheses in seven, and homografts in four. Follow-up information was available in 20 of 22 patients (84%). At mean follow-up of 5 years, there were 10 late deaths, due to: intracerebral hemorrhage (2), heart failure (2), unknown cause (2), renal failure (1), AIDS (1), sepsis (1) and endocarditis (1). Of the 20 patients with active preoperative endocarditis, 4 (20%) developed recurrent endocarditis; freedom from recurrent endocarditis was 83% at 1 year. Intravenous drug abuse was reported in 16 patients; survival among these patients was 94% at 1 month and 50% at 5 years. Recurrent endocarditis was only seen in patients with continued intravenous drug abuse. CONCLUSIONS: Valve replacement in HIV-infected patients has low operative risk, but late results are poor when HIV infection is associated with intravenous drug abuse, probably due to immunocompromise and continued high-risk behavior.

Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects.

BACKGROUND: A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model. METHODS: MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I-labeled MSCs (6 x 10(7)) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. RESULTS: Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% +/- 2.2% versus -3.37% +/- 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals. CONCLUSIONS: Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.

A new perspective in appendicitis: calculation of half time (T(1/2)) for perforation.

Appendicitis is generally a more serious disease in the elderly than in the young. In the former, perforation is seen commonly leading to the belief that the appendix perforates more readily and rapidly in the elderly. A competing view is that the appendix perforates relatively more frequently in the elderly than in the young. To distinguish between these two views we analyzed 126 cases of acute appendicitis stratified by age group. The time between onset of symptoms and perforation was calculated with a novel method that utilized the biological concept of T(1/2) for perforation. Our findings suggest that the rate of perforation in the elderly is not significantly different from that in the young but the frequency of perforation is higher in the elderly. We concluded that appendicitis carries a graver prognosis in the elderly because the frequency of appendiceal perforation is higher in the elderly.

Do statins have a role in the promotion of postoperative wound healing in cardiac surgical patients?

Cardiac surgical patients often have associated comorbidities that can impede normal wound healing; however, statin therapy has the potential to improve this process through augmentation of the normal inflammatory response. Outcomes included a 30% earlier rate of wound epithelialization and an 80% greater wound-breaking strength combined with faster wound healing rates (13.0 days vs 18.7 days, p<0.0001). Inhibition of farnesyl pyrophosphate may hold a key role in the mediation of such advantageous effects. This systematic review suggests that there is sufficient evidence to warrant completion of a human trial to assess the effects of statins on wound healing.

Do high-risk infants have a poorer outcome from primary repair of coarctation? Analysis of 192 infants over 20 years.

BACKGROUND: Balloon angioplasty for infant coarctation is associated with a high recurrence rate, making operative repair the gold standard for low-risk infants. Debate exists as to whether high-risk infants might be better served with primary angioplasty. We compared the outcome in high-risk versus low-risk infants over 20 years, in a center that always used surgical repair as the primary intervention. METHODS: Of 192 infants from 1986 to 2005, 56 were considered "high-risk," defined as requiring prostaglandin infusion together with either epinephrine infusion for 24 hours preoperatively, or ventilation and milrinone infusion for 24 hours preoperatively. All high-risk patients had a period of ventricular dysfunction prior to surgery, ranging from mild to severe. Outcomes were compared using Bonferroni comparison of means or the Fischer exact test as appropriate. RESULTS: Although the high-risk patients were smaller (3.3 ± 0.1 vs 4.2 ± 0.2 kg, p < 0.01), younger (18 ± 4 vs 57 ± 7 days, p < 0.01), and more often required a concomitant pulmonary artery band (25% vs 15%, p = 0.05), their cross-clamp times were the same as the low-risk patients (18.9 ± 0.9 vs 18.0 ± 0.4 minutes, p = 0.27) and there was no difference in postoperative morbidity (7% vs 3%, p = 0.11). However, there was a trend toward higher perioperative mortality (7% vs 2%, p = 0.07). When compared with the published studies of primary angioplasty in comparable high-risk infants, the mortality rate in our surgically treated high-risk group is much lower. Additionally, only 11% of our high-risk group required reintervention, with two-thirds treated successfully with a single angioplasty at 3.8 ± 2.2 years later, far lower than recurrence rates with primary angioplasty. CONCLUSIONS: We propose that primary surgical repair of coarctation in infants who are high risk should be the primary treatment, with angioplasty reserved for recurrent coarctation.

Pretreatment with omega-3 fatty acid infusion to prevent leukocyte-endothelial injury responses seen in cardiac surgery.

OBJECTIVE: Inappropriate multiorgan endothelial-leukocyte activation is major causative factor in organ dysfunction after cardiac surgery. We investigated in vitro, mechanism and magnitude of attenuation of the pathogenic response through pretreatment with an omega-3 fatty acid infusion. METHODS: Perioperative saphenous endothelial cell monolayers were pretreated and then stimulated with perioperative inflammatory mediators. Endothelial production of interleukin 6, interleukin 8, and adhesion molecules necessary for neutrophil tissue penetration, were examined, together with inflammatory endothelial coagulant responses. Pretreatment effects on isolated blood neutrophil inflammatory responses were similarly noted. Mechanistic insight was obtained through assessment of the temporal response of nuclear factor-kB and its association with heat shock protein 72(HSP72) expression. RESULTS: Four-hour pretreatment markedly reduced inflammatory endothelial release of interleukin 8 (2587 +/- 82 pg/mL control vs 208 +/- 3 pg/mL omega-3 pretreated, P < .01) and endothelial expression of intercellular adhesion molecule 1 (196.1 +/- 2.0 vs 71.9 +/- 0.6 mean channel fluorescence, P < .01) in response to endotoxin and tumor necrosis factor a. Neutrophil activation (CD11b and respiratory burst) was maintained, but pretreated neutrophils had shorter survival. Endothelial inflammatory stimulation produced rapid increase in nuclear activity of nuclear factor-kB, which was attenuated by 43% with omega-3 pretreatment (P < .01). This coincided with 3-fold increase (P = .03) in protective HSP72 expression with pretreatment. CONCLUSION: Acute pre-treatment with a clinically acceptable omega-3 infusion attenuates perioperative endothelial-neutrophil activation through transcription-level interaction.

Left atrial-inferior vena cava bypass achieves retroperfusion of the porcine spinal cord: morphologic and preliminary physiologic studies.

BACKGROUND: Spinal cord injury remains a devastating complication after procedures on the descending thoracic aorta. A new model for retrograde perfusion of the spinal cord during aortic cross-clamping was evaluated for its potential role in preventing spinal cord injury after thoraco-abdominal aortic surgery. METHODS: Retrograde perfusion of the spinal cord was established in juvenile pigs using partial bypass from the left atrium to the isolated inferior vena cava. Flow was maintained for a 60-min period of aortic occlusion. Morphologic studies of spinal cord blood flow were obtained using injection of a dilute barium-gelatin-chromatin dye solution. Physiologic cooling of the spinal cord was achieved using varying degrees of hypothermic retroperfusion. RESULTS: Five animals underwent a 30-min period of retroperfusion followed by dye injection. Dye was identified in spinal cord venules and capillaries, most heavily concentrated in the lumbar and lower thoracic cord. Thirteen animals underwent a 60-min period of normothermic (37 degrees C), mild hypothermic (27 degrees C), moderate hypothermic (17 degrees C), or deep hypothermic (7 degrees C) retroperfusion; mean spinal cord temperatures were 35.2, 32.2, 28.0, and 24.4 degrees C, respectively. CONCLUSIONS: Retrograde perfusion of the porcine spinal cord using a left atrial to inferior vena cava partial bypass circuit can be accomplished and can be used with hypothermic perfusate to produce cooling of the spinal cord. This new technique warrants further investigation into spinal cord protection and potential application for operations on the descending thoracic aorta.