Fate of the unoperated ascending thoracic aortic aneurysm: three-decade experience from the Aortic Institute at Yale University.

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.

Evidence Accumulates: Patients with Ascending Aneurysms Are Strongly Protected from Atherosclerotic Disease.

Ascending thoracic aortic aneurysms may be fatal upon rupture or dissection and remain a leading cause of death in the developed world. Understanding the pathophysiology of the development of ascending thoracic aortic aneurysms may help reduce the morbidity and mortality of this disease. In this review, we will discuss our current understanding of the protective relationship between ascending thoracic aortic aneurysms and the development of atherosclerosis, including decreased carotid intima-media thickness, low-density lipoprotein levels, coronary and aortic calcification, and incidence of myocardial infarction. We also propose several possible mechanisms driving this relationship, including matrix metalloproteinase proteins and transforming growth factor-ß.

"Big Data" Analyses Underlie Clinical Discoveries at the Aortic Institute.

This issue of the Yale Journal of Biology and Medicine (YJBM) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets). 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis: 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA.

Long-term risk of arch complications in Loeys Dietz syndrome patients undergoing proximal ascending aortic replacement.

PURPOSE: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder. In LDS patients with normal arch morphology, whether the arch should be prophylactically replaced at the time of proximal aortic replacement remains unknown. We evaluated the risk of long-term arch complications in genetically confirmed LDS patients who underwent proximal ascending aortic replacement. METHODS: We retrospectively reviewed the records of patients with LDS who have been followed at our institution between 1994 and 2020. Patients were only included if whole exome genetic testing confirmed a mutation in an LDS-causing gene (TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3). Mutations were categorized as pathogenic, benign, or of unknown significance. We collected demographic information, aortic dimensions, comorbidities, mortality, and operative course from patients' charts. Descriptive statistics and freedom from reoperation plots were generated. RESULTS: Of the 18 patients with a mutation in an LDS-causing gene, 15 had known pathogenic variants, two had mutations of unknown significance, and one had a benign genetic variant. For the 15 patients with confirmed pathogenic variants of LDS the median follow-up duration was 5 years (interquartile range [IQR]: 4-8). Eleven patients underwent ascending aortic replacements (AAR) ± aortic valve replacement. Two patients required an additional operation; one required arch and staged elephant trunk for a dissection 18 years post-AAR and the other patient required an isolated descending aortic replacement for dissection 5 years post-AAR. Among patients who underwent surgery, the median ascending aortic diameter at intervention was 5.0 cm (IQR: 4.3-5.3). There was no surgical or late follow-up mortality observed for any of the 18 patients in the study. CONCLUSION: LDS patients who underwent proximal aortic replacement appeared to have low long-term risk of arch complications. While our study is somewhat limited by its sample size and follow-up duration, it suggests that routine prophylactic total arch replacement may not be warranted in LDS patients with nonaneurysmal aortic arches.

Interstage mortality in two-stage elephant trunk surgery.

PURPOSE: Diffuse mega-aorta is challenging. Prior studies have raised concerns regarding the safety of the open two-stage elephant trunk (ET) approach for extensive thoracic aortic aneurysm (TAA), specifically in regard to interstage mortality. This study evaluates the safety of the two-stage ET approach for management of extensive TAA. METHODS: Between 2003 and 2018, 152 patients underwent a Stage I ET procedure by a single surgeon (mean age 64.5 ± 14.8). Second stage ET procedure was planned in 60 patients (39.4%) and to-date has been performed in 54 patients (90%). (in the remaining patients, the ET was prophylactic for the long-term, with no plan for near-term utilization). RESULTS: In-hospital mortality after the Stage I procedure was 3.3% (5/152). In patients planned for Stage II, the median interstage interval was 5 weeks (range: 0-14). Of the remaining six patients with planned, but uncompleted Stage II procedures, five patients expired from various causes in the interval period (interstage mortality of 8.3%). There were no cases of aortic rupture in the interstage interval. Stage II was completed in 58 patients (including four unplanned) with a 30-day mortality of 10.3% (6/58). Seven patients developed strokes after Stage II (12%), and three patients (5.1%) developed paraplegia. CONCLUSIONS: The overall mortality, including Stage I, interstage interval, and Stage II was 18.6%. This substantial cumulative mortality for the open two-staged ET approach for the treatment of extensive TAA appears commensurate with the severity of the widespread aortic disease in this patient group. Fear of interstage rupture should not preclude the aggressive Two-Stage approach to the management of extensive TAA.

Natural history and management of Kommerell's diverticulum in a single tertiary referral center.

OBJECTIVE: The Kommerell diverticulum (KD) is an extremely rare developmental abnormality of the aorta related to an aberrant subclavian artery (ASCA). The objective of our study was to review the natural history of KD and ASCA using our single-center experience in diagnosing and managing KD and ASCA. METHODS: A retrospective review of the Yale radiological database from January 1999 to December 2016 was performed. Only patients with KD/ASCA and a computed tomography (CT) scan of the chest were selected for review. The primary goal was to examine the natural history of KD and ASCA and the secondary goals were to review the management and outcomes of those patients treated for KD and ASCA. RESULTS: There were 75 patients with KD/ASCA identified, with a mean age of 63 ± 19 years; 49 were female (65%). On CT scans, left- and right-sided aortas were present in 47 (63%) and 28 (37%) patients. A right ASCA or a left ASCA were present in 47 (63%) and 28 (37%) patients. Six patients were symptomatic on presentation. Symptoms included dysphagia, chest or back pain, and emboli to the fingers. The mean KD diameter was 21.8 ± 6.0 mm and the distance to the opposite aortic wall (DAW) was 48.3 ± 10.8 mm. Sixty-six patients were followed for a mean of 31.7 ± 32.5 months. One patient ruptured without repair. Nine patients underwent operative intervention, including eight open and one endovascular repair. Complications from operative intervention included ischemic stroke with hemorrhagic transformation, deep vein thrombosis and pneumonia. The mean growth rate for KD and DAW was 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year, respectively. On multivariable regression analysis, hypertension was a predictor of growth of DAW (P = .03). CONCLUSIONS: KD is uncommon and shows a female predominance. The diverticulum grows, albeit slowly (KD and DAW growth rates of 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year). Most patients are asymptomatic, but dysphagia, chest/back pain, and distal emboli may occur. Rupture is rare. Symptomatic patients should be operated. Asymptomatic patients can be followed with serial CT scans.

Cine-Computed Tomography for the Evaluation of Prosthetic Heart Valve Function.

BACKGROUND: After aortic valve replacement (AVR), suspected prosthetic valve dysfunction (mechanical or biological) may arise based on echocardiographic transvalvular velocities and gradients, leading to reoperative surgical intervention being considered. Our experience has found that 4-dimensional (space and time) image reconstruction of ECG-gated computed tomography, termed cine-CT, may be helpful in such cases. We review and illustrate our experience. METHODS: Twenty-seven AVR patients operated previously by a single surgeon (who performs >100 AVRs/year) were referred for repeat evaluation of suspected aortic stenosis (AS) based on elevated transvalvular velocities and gradients. The patients were fully evaluated by cine-CT. RESULTS: In all but 2 cases, the cine-CT strikingly and visually confirmed normal leaflet function and excursion, with no valve thrombosis, restriction by pannus, or obstruction by clot. In only 2 cases did cine-CT reveal decreased mechanical valve leaflet excursion. Repeat surgery was required in only 1 case while all other patients continued clinically without cardiac events. CONCLUSIONS: Echocardiography is an extraordinarily useful tool for the evaluation of prosthetic valve function. Increased pressure recovery beyond the valve and other factors may occasionally lead to exaggerated gradients. Cine-CT is emerging as an extremely valuable tool for further evaluation of suspected prosthetic valve AS. Our experience has been extremely helpful, as is shown in the dramatically reassuring images.

The effects of ATP on the contractions of rat and mouse fast skeletal muscle.

INTRODUCTION: The aim of this study was to compare the effects of adenosine-5'-triphosphate (ATP) and adenosine on the contractility of rodent extensor digitorum longus (EDL) muscle at normal and low temperatures. METHODS: Contractions of rat and mouse isolated EDL were induced by either electrical stimulation (ES) or exogenous carbachol and recorded in the presence of ATP or adenosine (both at 100 µM). RESULTS: ATP at all temperatures caused a decrease of the contractions induced by carbachol in rat and mouse EDL and ES-induced contractions in rat EDL, while it potentiated the ES-induced contractions of mouse EDL. Adenosine reduced the contractility of rat and mouse EDL evoked by ES and did not affect the carbachol-induced contractions of rat and mouse EDL at any temperature. DISCUSSION: Under various temperature conditions, ATP inhibits pre- but potentiates postsynaptic processes in the mouse EDL; in the rat EDL ATP causes only inhibition of neuromuscular conduction. Muscle Nerve 59:509-516, 2019.

Routine anterior spinal artery visualization prior to descending and thoracoabdominal aneurysm repair: High detection success.

BACKGROUND: Paraplegia is adevastating complication of open descending (DTAA) and thoracoabdominal aortic aneurysm (TAAA) repair. Despite major advances in imaging and surgical techniques, paraplegia continues to be problematic. We present our experience with routine application of enhanced imaging techniques to detect the anterior spinal artery (ASA) before DTAA and TAAA repair. METHODS: We retrospectively reviewed 177 patients with DTAA and TAAA who underwent imaging to detect the ASA before open surgical repair. High definition CT angiography (CTA) and dual energy CT scanning (DECT) were our modalities of choice with angiography used earlier and magnetic resonance angiography (MRA) used when CT was contraindicated. Descriptive statistics and χ2 analyses were conducted. RESULTS: The imaging protocol successfully detected the level of the ASA in 132 (74.5%) patients, utilizing CTA in 67, DECT in 28, spinal angiography in 31, and MRA in 6. Cross sectional modalities with advanced visualization technique (CT, DECT, and MRA) were more successful at detecting the ASA than angiography (80.72%, 82.35%, 75% vs 59.62%, respectively, P = .04). Concerted efforts were made not to leave the operating room without continuity of the ASA with the circulation (via limited resection, beveled anastomosis, or reimplantation). Transient lower extremity weakness was observed in 11 (6.2%) patients, and permanent paraplegia in 2 (1.12%) patients. CONCLUSION: Modern imaging technology provides multiple methodologies highly successful at detecting the ASA. The ASA can then be preserved intraoperatively, contributing to low paraplegia rates. We strongly recommend routine application of this technology to arm the surgeon with precise information about the specific patient's spinal cord blood supply.

Fate of preserved bicuspid valves at time of ascending aortic aneurysmectomy.

BACKGROUND: The fate of the spared bicuspid aortic valve in patients undergoing ascending aortic aneurysm surgery is relatively unknown. Our institutional policy has been to replace all aortic valves with significant abnormalities, as evidenced by intraoperative transesophageal echocardiography or direct visual inspection. In this study, we elaborate our experience regarding the long-term fate of preserved bicuspid aortic valves after ascending aortic aneurysm extirpation. MATERIALS AND METHODS: From 2000 to 2018, 407 consecutive ascending aortic aneurysm patients with concomitant bicuspid aortic valves underwent surgery by a single surgeon at our institution. Among these, 23 (5.65%) patients did not have their valve replaced, forming the study group. Postoperative and preoperative echocardiograms were compared to determine changes in valve function. RESULTS: Follow-up was complete in 100% of patients. The average time between preoperative and postoperative echocardiograms was 4.50 ± 4.09 years (0.19-15.63). Aortic stenosis or regurgitation changed from none to mild in 5 (21.7%) of patients, with an average echocardiographic interval follow-up of 3.08 years, and from none to severe in 2 (8.7%), with an interval of 11.7 years. One patient required reoperation, including aortic valve replacement, during follow-up. CONCLUSION: Bicuspid aortic valves free of aortic stenosis or insufficiency before surgery and "healthy" appearing at surgery can safely be preserved.

Natural history and management of splanchnic artery aneurysms in a single tertiary referral center.

OBJECTIVE: Splanchnic artery aneurysms (SAAs) are rare, and little is known about their natural history and management. We reviewed our single-center experience in managing this population of patients. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with an SAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. Our primary outcomes included aneurysm growth rate and risk of rupture in those patients managed nonoperatively and morbidity and mortality of those SAA patients who underwent operative intervention. RESULTS: There were 122 patients with 138 SAAs identified; 77 were male (62%), with a mean age of 66 years (range, 25-94 years). On computed tomography, 56 (45%) had previously diagnosed or concomitant aneurysms elsewhere. Of the patients managed nonoperatively, 101 patients (79%) had 108 SAAs; in the operative intervention group, 25 (21%) patients had 30 SAAs. The mean overall vessel diameter was 1.76 ± 0.83 cm. The diameter of observed and operatively repaired SAAs was 1.58 ± 0.56 cm and 2.41 ± 1.23 cm, respectively (P = .00001). Mean follow-up was 50 ± 42 months for nonoperative management without any adverse events related to SAA, including 10 patients with SAA >2.0 cm. The mean observed growth rate for SAA was 0.064 ± 0.18 cm/y. All symptomatic patients who presented with severe abdominal pain (n = 11 [44%]) underwent operative intervention. Five patients presented with a ruptured SAA (3.6%; range, 2.3-5.0 cm); all of them except one underwent operative intervention. Other indications for repair included large size in seven, rapid growth in two, other open abdominal surgical procedures in two, multiple aneurysms in one, and desire to pursue fertility treatment in one. Operative repair included 14 (56%) endovascular embolizations and 11 (44%) open abdominal operations. After endovascular embolization, two patients underwent abdominal operation for hemorrhage and splenectomy. Open repairs included bypasses in six, splenectomy in two, resection in two, and plication in one. Two patients had postoperative acute kidney injury that resolved and one died of multisystem organ failure. One bypass occluded without sequelae. On multivariable regression analysis, female sex (P = .02) was associated with faster growth rate, and a history of smoking (P = .04) was associated with slower growth rate. CONCLUSIONS: It seems reasonable to observe asymptomatic patients with an SAA <2.0 cm because of the slow growth rate (0.064 ± 0.18 cm/y) and benign behavior. When intervention is needed, both open and endovascular options should be considered.

Natural history and management of renal artery aneurysms in a single tertiary referral center.

OBJECTIVE: Although renal artery aneurysms (RAAs) are uncommon, several large reports have been published indicating their benign natural history. The objective of our study was to review our single-center experience managing this disease entity. METHODS: A retrospective review of the Yale radiologic database from January 1999 to December 2016 was performed. Only patients with RAA and a computed tomography scan of the abdomen were selected for review. Demographics of the patients, aneurysm characteristics, management, postoperative complications, and follow-up data were collected. RESULTS: There were 241 patients with 259 RAAs identified, with a mean age of 69 years (range, 35-100 years); 147 were female (61%). On computed tomography, aneurysms were solitary and right sided in 224 (86%) and 159 (61%), respectively; 64 (27%) patients had aneurysms elsewhere. The breakdown of RAAs by location was as follows: renal bifurcation in 84 (32%), renal pelvis in 77 (30%), distal renal artery in 58 (22%), mid renal artery in 34 (13%), and proximal renal artery in 6 (2%). Five patients had symptoms that were attributed to the RAA and underwent operative repair; all others were observed without an operation. Symptoms in the operative repair group included flank pain in four and uncontrolled hypertension in one. The mean overall diameter of the RAAs was 1.22 ± 0.49 cm. The diameter of operatively repaired and observed RAAs was 1.84 ± 0.55 cm and 1.21 ± 0.48 cm, respectively (P = .002). Operative repair included four coil embolizations and one open resection. There were no renal function changes in any of these patients after operation and no other complications. Mean follow-up was 41 ± 35 months for patients in the group that was observed; 18 of these RAAs were >2 cm, and none ruptured. On multivariable regression analysis, female sex (P = .0001), smoking history (P = .00007), left-sided RAA (P = .03), and main renal artery location (P = .03) were inversely related to growth, whereas a history of hypertension was directly related to growth rate (P = .01). The mean growth rate for RAAs was 0.017 ± 0.052 cm/y. CONCLUSIONS: RAAs tend to have a benign natural history. Although previous reports have not identified any factors that contribute to RAA growth, we observed that RAA location, sex, smoking history, and hypertension may have an impact on growth rates. No ruptures were observed. Operative repair at our institution was rare, with no morbidity or mortality. Observation of RAAs over time seems feasible in the asymptomatic patient with a small RAA.

Natural history of aneurysmal aortic arch branch vessels in a single tertiary referral center.

OBJECTIVE: Little is known about the natural history and management of aneurysmal aortic arch branch vessels (AABVs). The objectives of this study were to assess the natural history of aneurysmal AABVs and to examine the outcomes of operative intervention. METHODS: A retrospective review of the Yale radiologic database from 1999 to 2016 was performed. Only those patients with an aneurysmal AABV and a computed tomography scan were selected for review. Patients' demographics, aneurysm characteristics, management, and follow-up information were collected. RESULTS: There were 105 patients with 147 aneurysmal AABVs; 76 were male (72%), with a mean age of 70 years (range, 17-93 years). We identified 63 innominate, 50 left subclavian, 30 right subclavian, and 4 common carotid artery aneurysms. On computed tomography, 65 (62%) had aortic aneurysms and six (6%) had suffered an aortic dissection. Most were asymptomatic (104 [99%]); one had chest pain and an enlarging swollen mass. Twelve (11%) patients underwent operative repair (OR) for 12 aneurysmal AABVs because of symptoms, growth, or concomitant aortic operations; 93 (89%) were observed in the no operative repair (NOR) group with cross-sectional imaging. The overall mean vessel diameter was 2.08 ± 0.68 cm. The mean diameters in the OR and NOR groups were 3.32 ± 1.24 cm and 1.97 ± 0.46 cm, respectively (P = .002). OR included nine bypasses with resection, two stent grafts, and one resection without reconstruction. Two patients developed postoperative hemorrhage requiring re-exploration, one patient developed stent thrombosis, and one patient required pseudoaneurysm repair 20 years after index operation. Mean follow-up was 52 ± 51 months for the NOR group, with no ruptures or emboli. The growth rate was 0.04 ± 0.10 cm/y. On multivariable regression analysis, a descending aortic aneurysm (P = .041) and a left subclavian artery aneurysm (P = .016) were associated with higher growth rates, whereas height was associated with a lower growth rate (P = .001). CONCLUSIONS: Aneurysmal AABVs tend to have a benign natural history with slow growth rates and low rates of complications, including rupture and embolization. We recommend expectant observational management for small, incidentally detected aneurysms.

Diabetes Mellitus: Is It Protective against Aneurysm? A Narrative Review.

OBJECTIVES: In the course of extensive clinical aortic surgery, we noticed that the aorta was quite thick and fibrotic in diabetic patients. We thought the diabetic aortic aorta might be inimitable to aortic dissection. On this basis, we set out to review information in the literature regarding aortic growth and dissection in diabetic patients. METHODS: We used a 2-step search approach to the available literature on diabetes and aneurysm. Firstly, databases including PubMed, Cochrane, Embase and TRIP were searched. Secondly, relevant studies were identified through secondary sources including references of initially selected articles. We address the relationship between diabetes and the incidence, prevalence, growth, mortality and rupture of an aneurysm. RESULTS: Diabetes is thought to exert a protective role in both thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Diabetics were shown to have a slower aneurysm growth rate, lower rupture rate, delayed (> 65 years) age of rupture, decreased rate of mortality from an aneurysm and a decreased length of hospital stay. There was also noted a decreased rate of incidence and prevalence of TAA and AAA in diabetics, smaller aneurysm diameter, reduction in matrix metalloproteinases and an increased aortic wall stress in diabetics. Antidiabetic agents like metformin, thiazolidinediones and dipeptidyl peptidase-4 inhibitors may protect against an aneurysm. CONCLUSION: Our literature review provides strong (but often circumstantial) evidence that diabetic patients exhibit slower growth of aortic aneurysms and a lower rate of aortic dissection. Furthermore, clinical and experimental studies indicate that common antidiabetic medications on their own inhibit growth of aortic aneurysms. These findings indicate a paradoxically beneficial effect of the otherwise highly detrimental diabetic state.

Antithrombotic Therapy after Bioprosthetic Aortic Valve Replacement: A Therapeutic Morass.

Valvular heart disease is a common pathologic condition that affects 6 million people in the United States and more than 100 million worldwide. The most common valvular disorder is aortic stenosis. Current American and European guidelines recommend surgical management for symptomatic aortic stenosis with low risk of perioperative complications and endovascular intervention for high-risk patients with multiple comorbidities. Considering the increasing volume of aortic valve replacement (AVR) with biological valves, it is very important to select the appropriate anticoagulant after surgical AVR. In this article, we review the impact of anticoagulation on immediate and remote complications after AVR.

Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size Threshold for Intervention.

BACKGROUND: Multiple studies have quantified the relationship between aortic size and risk of dissection. However, these studies estimated the risk of dissection without accounting for any increase in aortic size from the dissection process itself. OBJECTIVES: This study aims to compare aortic size before and after dissection and to evaluate the change in size consequent to the dissection itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with aortic dissection and incidental imaging studies prior to dissection were identified and compared to a control group of aneurysm patients (n = 205). The average time between measurement at and prior to dissection was 1.7 ± 1.9 years (1.9 ± 2.0 years mean inter-image time in the control group). A multivariate regression model controlling for growth rate, age, and gender was created to estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic sizes at and prior to dissection were 54.2 ± 7.0 and 45.1 ± 5.7 mm for the ascending aorta, and 47.1 ± 13.8 and 39.5 ± 13.1 mm for the descending aorta, respectively. The multivariable analysis revealed a significant impact of the dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS: The aortic diameter increases substantially due to aortic dissection itself and, thus, aortas are being dissected at clinically meaningfully smaller sizes than natural history analyses have previously suggested. These findings have important implications regarding the size at which the risk of dissection is increased.

Effects of ATP and adenosine on contraction amplitude of rat soleus muscle at different temperatures.

INTRODUCTION: The aim of this study was to evaluate the effects of adenosine 5'-triphosphate (ATP) and adenosine on the contractility of mammalian skeletal muscle under hypothermic conditions. METHODS: Contractions of isolated rat soleus muscle were induced by either electrical stimulation (ES) or carbachol at physiological temperatures (37°C) and hypothermic conditions (30-14°C) and recorded in the presence of ATP, adenosine, suramin, and 8-(p-sulfophenyl)-theophylline (8-SPT). RESULTS: At 37°C, incubation of the muscles with ATP inhibited ES-induced contractions; the inhibitory effect of ATP disappeared at 14°C. Adenosine inhibited ES-induced contractions at all temperature levels; 8-SPT fully prevented the action of adenosine. ATP and adenosine did not significantly affect carbachol-induced contractions at 37°C, while at lower temperatures ATP potentiated them. Suramin fully prevented effects of ATP. CONCLUSIONS: ATP is involved in both pre- and postsynaptic regulation of rat soleus muscle contractility, and these processes are significantly more pronounced at low temperatures. Muscle Nerve 55: 417-423, 2017.

Twenty-five year outcomes following composite graft aortic root replacement.

BACKGROUND: Operative choices for aortic root disease include traditional root replacement with a composite valved graft as well as various valve-sparing and root repair procedures. OBJECTIVES: To report our experience with traditional composite graft aortic root replacement by a single surgeon over a 25-year period in 449 patients, focusing on long-term survival and freedom from late reoperation and adverse events. METHODS: The coronary button technique was used in all patients. Mean age was 56.1 ± 14.0 years (range 14-87) with 83% males (373/449). Valve prosthesis was mechanical in 343 (76%) and bioprosthetic in 106 (24%). A modified Cabrol procedure (Dacron coronary graft) was employed in 10% (45/449) and concomitant coronary artery bypass graft in 10.9% (49/449). There were 15.8% (71/449) urgent/emergent and 8.2% (37/449) redo procedures. Survival follow-up was 100%. Mean follow-up was 7.0 ± 5.1 years (range 0.1-24.8). RESULTS: Operative mortality occurred in 14 patients (3.1%) and was 2.2% (9/418) in non-dissection and 1.9% (7/361) in elective first-time operations. Stroke and re-exploration for bleeding occurred in nine (2.0%) and 20 (4.5%) patients, respectively. Major late events included bleeding in 2.5% (11/435) and thromboembolism in 1.1% (5/435). At 5, 10, and 20 years, freedom from major events and reoperations on the root were 97.8, 95.4, and 94.39%, and 99.0, 99.0, and 97.9%, respectively. Survival in patients aged <60 years was 92.0, 90.1, and 79.8% at five, 10, and 20 years versus 88.4, 67.9, and 42.6% in patients aged ≥60 years (p = 0.001). Compared with age- and gender-matched controls, survival was not significantly different (p = 0.20). CONCLUSIONS: Composite graft aortic root replacement is associated with low operative risk, excellent long-term survival, and low incidence of reoperation and late events.

Developing medical education capacity in Russia: twenty years of experience.

BACKGROUND: The partnership between Yale University (USA) and Kazan State Medical University (KSMU, Russia) was established in 1996 and transitioned to Western Connecticut Health Network (WCHN)/University of Vermont Robert Larner, M.D. College of Medicine (USA) in 2012 with the goal of modernizing medical education at KSMU primarily through introduction of the American medical education structure, role modeling, and educational capacity building. It was centered on the formation of a select group of Russian junior faculty members familiar with American medical education who would then initiate a gradual change in medical education at KSMU. Here we describe the 20 year partnership, rooted in local capacity building, through which a sustainable, mutually rewarding international collaboration was established. In addition, we evaluate the program's outcomes and impact on medical education at Kazan State Medical University, and assess its influence on Russian program participants. METHODS: Senior residents and faculty were sent to KSMU to conduct teaching sessions with local faculty and trainees. Their responsibilities included familiarizing Russian colleagues with specific topics in clinical medicine, importing knowledge about the basics of teaching, clinical epidemiology and evidence based medicine, and creating, in consistency with the American model, a "Clinical Teaching Team Structure" that integrates patient care with clinical education. Furthermore, 44 of selected KSMU members, including 13 junior faculty (29.5%), 14 clinical PhD students (31.8%), 12 interns/residents (27.3%), and five medical students (11.4%), were trained at Yale/WCHN or one of their major affiliated community hospitals for a period of 1 to 12 months for a total of 844 participant-weeks of training. RESULTS: Thirty (68.2%) individuals who were trained in the U.S. are currently working in Kazan primarily as faculty at KSMU. Among them, three trainees (10%) have become heads of their department, eight (26.7%) hold senior faculty positions, and two (6.7%) have clinical and educational administrative leadership positions. Two major clinical departments have adopted the "Clinical Teaching Team Structure." As a result of the collaboration, three teaching courses - Evidence-Based Medicine, Tropical Medicine, and HIV/AIDS Medicine - have been designed and incorporated into the curriculum. CONCLUSION: This partnership has been instrumental in introducing the American medical education model and expanding the medical knowledge of faculty, residents, and students of KSMU on infectious diseases, HIV/AIDS, tropical medicine, renal diseases, and global health topics. Capacity building through the Yale/WCHN-KSMU exchange program has greatly contributed to the quality of medical education at Kazan State Medical University.