Rita K. Milewski

Hop is an unusual homeobox gene that modulates cardiac development.

Hop is a small, divergent homeodomain protein that lacks certain conserved residues required for DNA binding. Hop gene expression initiates early in cardiogenesis and continues in cardiomyocytes throughout embryonic and postnatal development. Genetic and biochemical data indicate that Hop functions directly downstream of Nkx2-5. Inactivation of Hop in mice by homologous recombination results in a partially penetrant embryonic lethal phenotype with severe developmental cardiac defects involving the myocardium. Inhibition of Hop activity in zebrafish embryos likewise disrupts cardiac development and results in severely impaired cardiac function. Hop physically interacts with serum response factor (SRF) and inhibits activation of SRF-dependent transcription by inhibiting SRF binding to DNA. Hop encodes an unusual homeodomain protein that modulates SRF-dependent cardiac-specific gene expression and cardiac development.

Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret

Hirschsprung disease and Waardenburg syndrome are human genetic diseases characterized by distinct neural crest defects. Patients with Hirschsprung disease suffer from gastrointestinal motility disorders, whereas Waardenburg syndrome consists of defective melanocyte function, deafness, and craniofacial abnormalities. Mutations responsible for Hirschsprung disease and Waardenburg syndrome have been identified, and some patients have been described with characteristics of both disorders. Here, we demonstrate that PAX3, which is often mutated in Waardenburg syndrome, is required for normal enteric ganglia formation. Pax3 can bind to and activate expression of the c-RET gene, which is often mutated in Hirschsprung disease. Pax3 functions with Sox10 to activate transcription of c-RET, and SOX10 mutations result in Waardenburg-Hirschsprung syndrome. Thus, Pax3, Sox10, and c-Ret are components of a neural crest development pathway, and interruption of this pathway at various stages results in neural crest-related human genetic syndromes.

Have hybrid procedures replaced open aortic arch reconstruction in high-risk patients? A comparative study of elective open arch debranching with endovascular stent graft placement and conventional elective open total and distal aortic arch reconstruction

OBJECTIVE Open total arch procedures have been associated with significant morbidity and mortality in patients with multiple comorbidities. Aortic arch debranching with endovascular graft placement, the hybrid arch procedure, has emerged as a surgical option in this patient population. This study evaluates the outcomes of a contemporary comparative series from one institution of open total arch and hybrid arch procedures for extensive aortic arch pathology. METHODS From July 2000 to March 2009, 1196 open arch procedures were performed, including 45 elective and 7 emergency open total arch procedures. From 2005 to 2009, 64 hybrid arch procedures were performed: 37 emergency type A dissections and 27 elective open arch debranchings. Hemiarch procedures were excluded. RESULTS The hybrid arch cohort was significantly older (P = .008) and had greater predominance of atherosclerotic pathophysiology (P < .001). The incidence of permanent cerebral neurologic deficit was similar at 4% (1/27) for the hybrid arch cohort and 9% (4/45) for the open aortic arch cohort. In-hospital mortality was similar at 11% (3/27) for the hybrid arch cohort and 16% (7/45) for the open aortic arch cohort. However, in the open arch group, there was a significant difference in mortality between patients aged less than 75 years at 9% (3/34) and patients aged more than 75 years at 36% (4/11) (P = .05). CONCLUSIONS Hybrid arch procedures provide a safe alternative to open repair. This study suggests the hybrid arch approach has a lower mortality for high-risk patients aged more than 75 years. This extends the indication for the hybrid arch approach in patients with complex aortic arch pathology previously considered prohibitively high risk for conventional open total arch repair.

Retrograde and antegrade cerebral perfusion: results in short elective arch reconstructive times.

BACKGROUND Debate remains regarding optimal cerebral circulatory management during relatively noncomplex, short arch reconstructive times. Both retrograde cerebral perfusion with deep hypothermic circulatory arrest (RCP/DHCA) and antegrade cerebral perfusion with moderate hypothermic circulatory arrest (ACP/MHCA) have emerged as established techniques. The aim of the study was to evaluate perioperative outcomes between antegrade and retrograde cerebral perfusion techniques for elective arch reconstruction times less than 45 minutes. METHODS Between 1997 and September 2008, 776 cases from two institutions were reviewed to compare RCP/DHCA and ACP/MHCA perfusion techniques. At the University of Pennsylvania, 682 were treated utilizing RCP/DHCA cerebral protection. At the University of Bologna, 94 were treated with ACP/MHCA and bilateral cerebral perfusion. RESULTS Mean cerebral ischemic time and visceral ischemic time differed between RCP/DHCA and ACP/MHCA (p < 0.001). Multivariate analysis showed age more than 65 years, atherosclerotic aneurysm, and cross-clamp time as predictors of the composite endpoint of mortality, neurologic event, and acute myocardial infarction. There was no significant difference in permanent neurologic deficit, temporary neurologic dysfunction, or renal failure, between RCP/DHCA and ACP/MHCA. Mortality was comparable across both techniques. CONCLUSIONS Both RCP/DHCA and ACP/MHCA have emerged as effective techniques for selected aortic arch operations with low morbidity and mortality. Univariate analysis revealed no statistically significant differences in primary or secondary outcomes between techniques for aortic reconstruction times less than 45 minutes. Data from this study demonstrate that selective use of either RCP/DHCA or ACP/MHCA provides excellent cerebral and visceral outcomes for elective open aortic surgery with short arch reconstructive times.

How does the ascending aorta geometry change when it dissects

OBJECTIVES The purpose of this study is to delineate changes in aortic geometry and diameter due to dissection. BACKGROUND Aortic diameter is the major criterion for elective ascending aortic replacement for dilated ascending aortas to prevent aortic dissection. However, recommendations are made on the basis of clinical experience and observation of diameters of previously dissected aortas. METHODS Six tertiary centers on 2 continents reviewed their acute aortic dissection type A databases, which contained 1,821 patients. Included were all non-Marfan patients with nonbicuspid aortic valves who had undergone computed tomography angiography <2 years before and within 12 h after aortic dissection onset. Aortic geometry before and after dissection onset were compared. RESULTS Altogether, 63 patients were included (27 spontaneous and 36 retrograde dissections, median age 68 [57; 77] years; 54% were men). In all but 1 patient, maximum ascending aortic diameter was <55 mm before aortic dissection onset. The largest increase in diameter and volume induced by the dissection were observed in the ascending aorta (40.1 [36.6; 45.3] mm vs. 52.9 [46.1; 58.6] mm, +12.8 mm; p < 0.001; 124.0 [90.8; 162.5] cm(3) vs. 171.0 [147.0; 197.0] cm(3), +47 cm(3); p < 0.001). Mean aortic arch diameter increased from 39.8 (30.5; 42.6) mm to 46.4 (42.0; 51.6) mm (+6.6 mm; p < 0.001) and descending thoracic aorta diameter from 31.2 (27.0; 33.3) mm to 34.9 (30.9; 39.5) mm (+3.7 mm; p < 0.001). Changes in thoracic aorta geometry were similar for spontaneous and retrograde etiology. CONCLUSIONS Geometry of the thoracic aorta is affected by aortic dissection, leading to an increase in diameter that is most pronounced in the ascending aorta. Both spontaneous and retrograde dissection result in similar aortic geometry changes.

Classic hybrid evolving approach to distal arch aneurysms: Toward the zone zero solution

BACKGROUND A combined open surgical and endovascular approach to managing aneurysms of the distal aortic arch (hybrid arch repair) is evolving as a viable treatment option. Our aim is to describe a treatment strategy in high-risk patients and report the technical and clinical success of the hybrid approach to aneurysms involving the distal aortic arch. METHODS From July 2005 until December 2009, 27 consecutive patients with aneurysms of the distal aortic arch were treated via a hybrid arch repair. Of this group, 23 patients underwent aortic arch debranching and revascularization before endovascular stent deployment in the ascending aorta (type I). Four patients required ascending aortic and transverse arch replacement before stent graft deployment (type II). RESULTS A stent graft was successfully deployed in 100% of patients after aortic arch vessel debranching via median sternotomy. The mean age of the patients was 71 ± 7.5 years. The average cardiopulmonary bypass time was 199 ± 84 minutes with an average crossclamp time of 57 ± 53 minutes. Deep hypothermic circulatory arrest was required in 4 patients (all type II). The average length of stay was 17.2 ± 14 days. The complications included stroke in 3 (11%) patients, permanent paralysis in 2 (7%), and perioperative death in 3 (11%) patients. CONCLUSIONS Early results of type I and II hybrid arch repair, in this cohort of patients with mutiple comorbid risk factors, are acceptable and even encouraging. This evolving approach to aneurysms involving the aortic arch may extend the indications for use of endovascular prostheses in the treatment of patients with complex aortic arch disease.

Transapical Deployment of Endovascular Thoracic Aortic Stent Graft for an Ascending Aortic Pseudoaneurysm

We report a case of a patient with a history of previous coronary artery bypass grafting undergoing endovascular aortic repair of a large pseudoaneurysm in the ascending aorta. Due to the limitations of the current technology, the endograft was deployed through a left ventricular transapical approach by using a left mini-thoracotomy.

Surgical treatment of bicuspid aortic valve disease: Knowledge gaps and research perspectives

Supplemental material is available online.Sempre la praticadeveessereedificata sopra la bonateorica. [Practice must always be founded on soundtheory.]—Leonardo Da Vinci (1452-1519; providedthe firstdepiction of abicuspid aorticvalve).Research on bicuspid aortic valves (BAV) and associatedconditions is increasing exponentially. A major part of thecurrent knowledge on BAV is derived from investigationscarried out in the clinical setting, especially the surgicalsetting, as a consequence of the epidemiologic and surgicalimportance of its valvular and vascular complications. Forexample, most of the stenotic valves explanted at the timeof aortic valve replacement are congenitally malformed.

Graft Selection for Aortic Root Replacement in Complex Active Endocarditis: Does It Matter?

BACKGROUND Endocarditis affecting the aortic valve, with abscess formation and root destruction, remains a challenge to treat. Aortic root homografts have been advocated because of a perceived lower risk of infective complications than with other root replacement grafts. However, the theoretical advantage of homografts has not been re-evaluated in the modern era. This report is based on an examination of our results for all aortic root replacements in complex, active endocarditis affecting the aortic valve. METHODS From 2000 to 2010, 134 patients (70.9% male; mean age 58.3±14.8 years) at our institution underwent aortic root replacement for active endocarditis. Ninety of the patients (67.2%) had a previously implanted prosthetic aortic valve. Our findings for these patients included one or more of the following: abscess (n=110, 82.1%), valve vegetation (n=98, 73.1%), and pseudoaneurysm or rupture or both (n=62, 46.3%). We retrospectively reviewed data for the patients from hospital records and the social security data base. RESULTS A mechanical composite graft (MC) was used in 43 of the patients (32.1%), a non-homograft biologic valve conduit (BC) in 55 patients (41.0%), and a homograft (HG) valve in 36 patients (26.9%). There was no significant difference among the groups in the incidence of major complications or in-hospital mortality. During a mean follow-up of 32.1±29.4 months, the rates of readmission, reinfection, and reoperation were similar for the three groups. The mean 5-year survival in the study was 58±9% for the MC group, 62±7% for the BC group, and 58 ± 9% for the HG group, respectively (p=0.48). CONCLUSIONS Aortic root replacement in the presence of complex active infection is associated with significant morbidity and mortality. We report that the rates of major complications and late mortality were similar among MC, BC, and HG groups in our study.

Long-term results of aggressive hemiarch replacement in 534 patients with type A aortic dissection

OBJECTIVE To present the outcomes of routinely performed hemiarch replacement in patients with acute type A aortic dissection. METHODS From 1993 to 2013, among 629 patients with acute type A dissection, 534 patients (85%) underwent hemiarch, 63 patients (10%) underwent hemiarch and antegrade thoracic stent grafting, 26 patients (4%) underwent total arch, and 6 patients (1%) underwent isolated ascending replacement. Patients with hemiarch replacement comprised the study population. Median follow-up was 4.1 years (first quartile, 1.9; third quartile, 7.8) (2462 patient years). RESULTS In-hospital mortality was 12% (66 out of 534 patients). Survival was 80% ± 2%, 68% ± 3%, and 51% ± 3%, and 84% ± 3%, 65% ± 4%, and 41% ± 6% in DeBakey type I and II patients at 1, 5, and 10 years, respectively (log rank P = .375). Freedom from distal aortic reintervention was 97% ± 1%, 90% ± 2%, and 85% ± 3% and 99% ± 1%, 97% ± 2%, and 90% ± 5% in DeBakey type I and II patients at 1, 5, and 10 years, respectively (log rank P = .046). Seven patients (1.3%) required reintervention for aortic arch aneurysm and 25 patients (5%) required reintervention for descending aortopathy. The success rate for distal reintervention performed electively or urgently was 92% (24 out of 26 patients). Marfan syndrome (odds ratio, 3.43; P = .046) and DeBakey type I dissection (odds ratio, 2.49; P = .048) were independent predictors of distal aortic reintervention. CONCLUSIONS Aggressive hemiarch replacement in acute type A dissection can be performed with low mortality and low aortic arch reoperation rate. Resection of all dissected aortic wall tissue decreases, but does not eliminate, the risk of later adverse aortic events.