Midterm experience with modified Cabrol procedure: Safe and durable for complex aortic root replacement

ObjectiveTo evaluate the early and late outcomes of the modified Cabrol technique as a method of coronary reimplantation during complex composite graft replacement of the ascending aorta.MethodsBetween 1995 and 2012, 348 patients (mean age, 56 ± 14 years; 283 males and 65 females) underwent composite graft replacement of the ascending aorta, 40 of whom (mean age, 60 ± 12 years; 35 males and 5 females) had one or both coronary ostia reimplanted using a modified Cabrol technique with an 8- to 10-mm Dacron interposition graft. The mean clinical and radiologic (computed tomographic scan) postoperative follow-up was 39 months (range, 1-171 months), via our aortic database, patient interviews, and Social Security Death Index.ResultsCabrol reimplantation was necessitated by reoperations with anatomically fixed coronary ostia (n = 16, 40%), severely displaced coronary arteries (n = 15, 37.5%), button calcification (n = 4, 10%), coronary anomalies (n = 3, 7.5%), and coronary aneurysm (n = 2, 5%). Of the operations, 20% (8 patients) were urgent interventions. Early mortality was 3 (7.5%) of 40, none related to the Dacron interposition graft. Total late mortality was 16.2%, also not related to the coronary graft. Actuarial survivals were 0.88 ± 0.05, 0.79 ± 0.07, and 0.73 ± 0.08 at 1, 3, and 6 years, respectively. Radiologic follow-up was available for 31 (83.8%) of the surviving patients and revealed that the interposition graft was widely patent in all.ConclusionsThe modified Cabrol technique using a Dacron interposition graft showed good survival rates and excellent durability over time, confirmed radiographically. These data confirm that it is appropriate to use the Cabrol technique when technical complexity prevents bringing coronary buttons to the main aortic graft

Training Young Russian Physicians in Uganda: A Unique Program for Introducing Global Health Education in Russia

Background: Global health is a new concept in Russia. There has been an ongoing academic collaboration between the Yale School of Medicine in the United States and Makerere University College of Health Sciences in Uganda since 2010, and the US Western Connecticut Health Network/University of Vermont College of Medicine since 2012, to introduce global health concepts to Kazan State Medical University (KSMU) in Russia. The purpose was to educate Russian physicians and medical trainees about the practice of clinical medicine and medical education, as well as the general practice of global health in culturally diverse, resource-limited settings. Objectives: The aim of this study was to evaluate the initial outcomes of this multi-institutional partnership and to assess the impact of the global health elective on the participants and on KSMU. Methods: Participants were selected to attend a 6-week elective in global health at Mulago Hospital in Kampala, Uganda. The elective consisted of clinical experience, education about Uganda's common diseases, and region-specific sociocultural classes. It included a predeparture orientation and, upon return, completion of a standard questionnaire to assess the program's impact. Results: Since 2010, there have been 20 KSMU members (4 medical students, 4 interns, 9 residents, 2 fellows, and 1 faculty member) who have participated in the program. As a result of the elective, the participants reported increased knowledge of tropical medicine (70%) and HIV/AIDS (75%), and 95% reported increased cultural sensitivity and desire to work with the underserved. The majority noted a very positive impact of their careers (90%) and personal life (80%). KSMU established the first successful collaborative program in global health education in Russia, leading to the integration of tropical medicine and global health courses in medical school curriculum. Conclusion: This elective has proven highly effective in introducing the concept of global health to faculty, fellows, residents, and medical students at KSMU. It trained these participants to address the challenges faced by physicians in culturally diverse and resource-limited countries

Targeted genetic analysis in a large cohort of familial and sporadic cases of aneurysm or dissection of the thoracic aorta

PURPOSE: Thoracic aortic aneurysm/aortic dissection (TAAD) is a disorder with highly variable age of onset and phenotype. We sought to determine the prevalence of pathogenic variants in TAAD-associated genes in a mixed cohort of sporadic and familial TAAD patients and identify relevant genotype–phenotype relationships. METHODS: We used a targeted polymerase chain reaction and next-generation sequencing–based panel for genetic analysis of 15 TAAD-associated genes in 1,025 unrelated TAAD cases. RESULTS: We identified 49 pathogenic or likely pathogenic (P/LP) variants in 47 cases (4.9% of those successfully sequenced). Almost half of the variants were in nonsyndromic cases with no known family history of aortic disease. Twenty-five variants were within FBN1 and two patients were found to harbor two P/LP variants. Presence of a related syndrome, younger age at presentation, family history of aortic disease, and involvement of the ascending aorta increased the risk of carrying a P/LP variant. CONCLUSION: Given the poor prognosis of TAAD that is undiagnosed prior to acute rupture or dissection, genetic analysis of both familial and sporadic cases of TAAD will lead to new diagnoses, more informed management, and possibly reduced mortality through earlier, preclinical diagnosis in genetically determined cases and their family members

Straight deep hypothermic circulatory arrest for cerebral protection during aortic arch surgery: Safe and effective

ObjectiveTo evaluate our extensive clinical experience using deep hypothermic circulatory arrest (DHCA) as a sole method of cerebral protection during aortic arch surgery, with an emphasis on determining the safe duration of DHCA.MethodsA total of 490 consecutive patients (303 males [61.8%], mean age, 62.7 ± 13.5 years) underwent surgical interventions on the aortic arch with straight DHCA for cerebral protection. Of the procedures, 65 (13.3%) were either urgent or emergency. Aortic aneurysms (n = 417, 85.1%) and dissections (n = 71, 14.5%) were the main indications for surgery.ResultsThe mean DHCA duration was 29.2 ± 7.9 minutes at a mean bladder temperature of 18.7°C. The overall mortality was 2.4% (12 of 490), and elective mortality was 1.4% (6 of 425). The seizure rate was 1.4% (7 of 490). Six patients (1.2%) developed renal failure that required dialysis. The postoperative stroke rate was 1.6% (8 of 490) and was 1.2% (5 of 425) for the elective cases. The overall stroke rate for patients requiring <50 minutes of DHCA was 1.3% (6 of 478), significantly different from the 16.7% (2 of 12) stroke rate for patients requiring >50 minutes of DHCA (P = .014). Multivariate analysis revealed a DHCA time >50 minutes (odds ratio, 5.11 ± 4.01, P = .038) and aortic dissection (odds ratio, 3.59 ± 1.72, P = .008) to be strong predictors of composite adverse outcomes.ConclusionsStraight DHCA is a safe and effective technique of cerebral protection for the absolute majority of interventions involving the aortic arch. At experienced centers, up to 50 minutes of DHCA can be considered safe, without significant postoperative mortality or neurologic sequelae

Phenotyping Zebrafish Mutant Models to Assess Candidate Genes Associated with Aortic Aneurysm

(1) Background: Whole Exome Sequencing of patients with thoracic aortic aneurysm often identifies “Variants of Uncertain Significance” (VUS), leading to uncertainty in clinical management. We assess a novel mechanism for potential routine assessment of these genes in TAA patients. Zebrafish are increasingly used as experimental models of disease. Advantages include low cost, rapid maturation, and physical transparency, permitting direct microscopic assessment. (2) Methods: Zebrafish loss of function mutations were generated using a CRISPRC/CAS9 approach for EMILIN1 and MIB1 genes similar to VUSs identified in clinical testing. Additionally, “positive control” mutants were constructed for known deleterious variants in FBN1 (Marfan’s) and COL1A2, COL5A1, COL5A2 (Ehlers-Danlos). Zebrafish embryos were followed to six days post-fertilization. Embryos were studied by brightfield and confocal microscopy to ascertain any vascular, cardiac, and skeletal abnormalities. (3) Results: A dramatic pattern of cardiac, cerebral, aortic, and skeletal abnormalities was identified for the known pathogenic FBN1 and COL1A2, COL5A1, and COL5A2 mutants, as well as for the EMILIN1 and MIB1 mutants of prior unknown significance. Visualized abnormalities included hemorrhage (peri-aortic and cranial), cardiomegaly, reduced diameter of the aorta and intersegmental vessels, lower aortic cell counts, and scoliosis (often extremely severe). (4) Conclusion: This pilot study suggests that candidate genes arising in clinical practice may be rapidly assessed via zebrafish mutants—thus permitting evidence-based decisions about pathogenicity. Thus, years-long delays to clinically demonstrate pathogenicity may be obviated. Zebrafish data would represent only one segment of analysis, which would also include frequency of the variant in the general population, in silico genetic analysis, and degree of preservation in phylogeny

Aortic Valve Replacement in the Failing Left Ventricle: Worthwhile?

Purpose: According to the 2020 American College of Cardiology/American Heart Association guidelines, the aortic valve should be replaced in the setting of severe aortic stenosis or regurgitation, independent of left ventricular function (even for EF <55%). However, in clinical practice, especially in a very low EF range, surgeons may avoid surgical aortic valve replacement (SAVR) because of concern over operative risk. This study examines outcomes of patients with EF ≤35% undergoing SAVR. Methods: From 2004 to 2019, 895 patients underwent SAVR for aortic stenosis (AS) and/or regurgitation (AR) by a single surgeon at our institution. From among these, 40 patients (4.47%) had an ejection fraction (EF) of 35% or less, forming the study group. Intra-aortic balloon pump was placed intraoperatively prophylactically pre-bypass in 18 out of the 40. Preoperative and post-operative echocardiograms were compared to determine changes in ejection fraction. Mid-term survival was assessed. Results: 16 patients presented with AS, 20 with AR, and 4 with a combination of AS and AR. Hospital survival was 97.5% (one patient death). The average ejection fraction progressively improved over time from 26% initially to 46% mid-term with mean follow-up of 43 months (0.1–140.7). Remarkably, five-year survival was comparable between the study group and an age- and gender-matched general population (p = 0.834). Downward trends in LV end-diastolic diameter and end-systolic diameter were seen. The former achieved statistical significance (6.0 cm to 5.3 cm; p = 0.0046), while the latter fell slightly short (4.8 cm to 4.1 cm; p = 0.056). Patients in whom an IABP was used had lower EFs than those without IABP (range 10–35, mean 23% vs. 15–35%, mean 27.6%). The EFs of the three subgroups improved significantly postoperatively (p < 0.001 for AS, p = 0.002 for AR, and p = 0.046 for AS and AR). Conclusions: Surgical AVR can be done safely in patients with a failing LV with EF ≤35%. Significant improvements in the ejection fraction are seen over time. We believe there is a role for prophylactic pre-bypass IABP. Five-year survival is normalized. Surgeons should not hesitate to perform AVR in these highly jeopardized patients