Maryann Tranquilli

Weight Lifting and Aortic Dissection: More Evidence for a Connection

Background/Aims: In 2003, we reported on a small number of patients in whom acute aortic dissection appeared to be causally related to intense weight lifting. If additional cases could be identified, the phenomenon of weight lifting induced aortic dissection would be further substantiated. We now report a substantially larger number of cases in which aortic dissection is associated with intense physical exertion. Methods: Additional cases of acute aortic dissection occurring at the time of intense physical exertion were accumulated and analyzed. Cases were culled from retrospective review of a large university data base and from reports forwarded to our attention from around the country. We determined type of activity bringing on symptoms, age and sex of the patients, location of the dissection (ascending or descending aorta), aortic size, therapy, and survival. Results: We identified 31 patients in whom acute aortic dissection occurred in the context of severe physical exertion, predominantly weight lifting or similar activities. All patients except one were males. Mean age was 47.3 (range = 19–76). All except four dissections were in the ascending aorta. Only three patients (9.7%) had a family history of aortic disease. Mean aortic diameter on the initial imaging study was 4.63 cm. Twenty-six of the 31 cases were diagnosed ante-mortem and 5 post-mortem. Overall, 10 of the 31 patients (32.2%) died. Of 24 patients reaching surgical therapy, 20 (83.3%) survived. Conclusion: Weight lifting related acute aortic dissection appears to be a real phenomenon, with increasing evidence for the association of extreme exertion with this catastrophic aortic event. Moderate aortic dilatation confers vulnerability to exertion-related aortic dissection. Individuals with known aortic dilatation should be cautioned to refrain from weight lifting or strenuous exertion. Routine echocardiographic screening of individuals engaging in heavy strength training should be considered, in order to prevent this tragic loss of life.

Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm

Background Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA. Methods and Findings Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78±6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan® real-time PCR assays. Classification based on the TaqMan® data replicated the microarray results and achieved 80% classification accuracy on the testing set. Conclusions This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan® real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA.

Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting

BACKGROUND Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES). Here we present our initial results. METHODS The WES was performed in 102 patients (mean age 56.8 years; range 13 to 83; 70 males [68.6%]) with TAAD. The following 21-gene panel was tested by WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2. RESULTS Seventy-four patients (72.5%) had no medically important genetic alterations. Four patients (3.9%) had a deleterious mutation identified in the FBN1, COL5A1, MYLK, and FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants of unknown significance were identified in 1 or more of the following genes: FBN1 (n = 5); MYH11 (n = 4); ACTA2 (n = 2); COL1A1 (n = 2); TGFBR1 (n = 2); COL3A1 (n = 1); COL5A1 (n = 1); COL5A2 (n = 1); FLNA (n = 1); NOTCH1 (n = 1); PRKG1 (n = 1); and TGFBR3 (n = 1). Identified mutations had implications for clinical management. CONCLUSIONS Routine genetic screening of patients with TAAD provides information that enables genetically personalized care and permits identification of novel mutations responsible for aortic pathology. Analysis of large data sets of variants of unknown significance that include associated clinical features will help define the mutational spectrum of known genes underlying this phenotype and potential identify new candidate loci.

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

OBJECTIVE To 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. METHODS A 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. RESULTS The 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. CONCLUSIONS Straight 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.

‘Bovine’ Aortic Arch – A Marker for Thoracic Aortic Disease

Objectives: Very few studies have addressed the clinical significance of ‘bovine’ aortic arch (BA). We sought to determine whether BA is associated with thoracic aortic disease, including thoracic aortic aneurysm, aortic dissection, aortic rupture, and accelerated aortic growth rate. Methods: We retrospectively reviewed CT and/or MRI scans of 612 patients with thoracic aortic disease and 844 patients without thoracic aortic disease to determine BA prevalence. In patients with thoracic aortic disease, we reviewed hospital records to determine growth rate, prevalence of dissection and rupture, and accuracy of radiology reports in citing BA. Results: 26.3% of the patients with thoracic aortic disease had concomitant BA, compared to 16.4% of the patients without thoracic aortic disease (p < 0.001). There was no association between BA and prevalence of dissection or rupture (p = 0.38 and p = 0.56, respectively). The aortic expansion rate was 0.29 cm/year in the BA group and 0.09 cm/year in the non-BA group (p = 0.004). Radiology reports cited BA in only 16.1% of the affected patients. Conclusions: (1) BA is significantly more common in patients with thoracic aortic disease than in the general population. (2) Aortas expand more rapidly in the setting of BA. (3) Radiology reports often overlook BA. (4) BA should not be considered a ‘normal’ anatomic variant.

Comparison of the Effect on Long-Term Outcomes in Patients With Thoracic Aortic Aneurysms of Taking Versus Not Taking a Statin Drug

The potential of medical therapy to influence the courses and outcomes of patients with thoracic aortic aneurysms is not known. The aim of this study was to determine whether statin intake is associated with improved long-term outcomes in these patients. A total of 649 patients with thoracic aortic aneurysms were studied, of whom 147 were taking statins at their first presentation and 502 were not. After a median follow-up period of 3.6 years, 30 patients (20%) taking statins had died, compared with 167 patients (33%) not taking statins (hazard ratio 0.68, 95% confidence interval 0.46 to 1, p = 0.049); 87 patients (59%) taking statins reached the composite end point of death, rupture, dissection, or repair compared with 378 patients (75%) not taking statins (hazard ratio 0.72, 95% confidence interval 0.57 to 0.91, p = 0.006). After adjustments for co-morbidities, the association between statin therapy and the composite end point was driven mainly by a reduction in aneurysm repairs (hazard ratio 0.57 95% confidence interval 0.4 to 0.83, p = 0.003). On Kaplan-Meier analysis, the survival rate of patients taking statins was significantly better (p = 0.047). In conclusion, the intake of stains was associated with an improvement in long-term outcomes in this cohort of patients with thoracic aortic aneurysms. This was driven mainly by a reduction in aneurysm repairs.

Femoral artery cannulation for thoracic aortic surgery: Safe under transesophageal echocardiographic control

OBJECTIVE Choice of cannulation site (femoral, axillary) for cardiopulmonary bypass for thoracic aortic surgery is controversial. We review a single-center consecutive experience with femoral cannulation in the era of transesophageal echocardiography (TEE). METHODS Femoral artery cannulation is our preference for both aneurysms and dissections. If intraoperative TEE (or preoperative computed tomography) shows mobile atheroma, we avoid femoral cannulation and use the right axillary artery. Charts were reviewed to detect any cannulation- or perfusion-related complications. RESULTS Eight hundred eighty patients underwent cannulation for cardiopulmonary bypass for thoracic aortic surgery: 767 femoral (87%) and 113 other (13%, 87 aortic, 22 axillary, 4 innominate). Among the femoral cases, 673 (87.7%) were elective and 94 (12.2%) urgent or emergency. Hospital survival was 723 of 767 (94%): 654 of 673 (97%) for elective cases and 69 of 94 (73%) for urgent or emergency cases. Survivals were 549 of 572 (95%) for ascending and arch, 91 of 97 (93%) for descending, and 83 of 98 (84%) for thoracoabdominal. Stroke (fixed neurologic deficit) occurred in 14 of 767 cases (1.8%): 9 ascending or arch and 5 descending or thoracoabdominal. There were 5 paraplegias in the descending or thoracoabdominal group. There was 1 instance of intraoperative descending dissection (well tolerated), no arterial ruptures, and 6 instances (0.7%) of local femoral arterial narrowing requiring surgical correction (patch graft). One patient (0.1%) had postoperative ischemia of the cannulated limb, and 25 patients (3.2%) had local wound problems (infection 21, seroma 4) treated conservatively. CONCLUSIONS This large experience in the TEE era strongly supports femoral cannulation for aortic surgery, with good survival, low stroke rate, minimal perfusion-related rupture or dissection, and minimal limb ischemia. If intraoperative TEE shows mobile atheroma, axillary cannulation is preferred.

Concurrent intracranial and thoracic aortic aneurysms.

The pathogeneses of both thoracic aortic aneurysm (TAA) and intracranial aneurysm (ICA) share common pathologic mediators. However, the prevalence of ICA in patients with TAA is not known. The present study investigated the prevalence of concurrent ICA to determine whether patients with TAA should be screened for ICA. The records of 212 patients with TAA and concurrent brain images (computed tomographic angiograms or magnetic resonance angiograms) were retrospectively analyzed. A bivariate statistical analysis (Fishers exact test) was used to compare the subgroups. We found that patients with TAA had a 9.0% prevalence of ICA (19 of 212 patients), ninefold greater than that in the general population. Also, the location of the TAA influenced the prevalence of ICA. The prevalence of ICA in patients with a descending TAA was significantly greater-33% (5 of 15 patients)-than the prevalence (7.1%) in patients (14 of 197 patients) with an ascending TAA (p = 0.006). Hypertension also increased the prevalence of concurrent ICA: 18 (11.8%) of 153 patients with hypertension and a TAA had concurrent ICA, but only 1 (1.7%) of 59 normotensive patients with a TAA had an ICA (p = 0.03). A history of cigarette smoking increased the risk of an ICA. Race, age, and gender did not significantly affect the prevalence of concurrent ICA. In conclusion, patients with a TAA are at increased risk of having an ICA. We suggest that patients with a TAA be screened for an ICA.

Atypical aortic arch branching variants: A novel marker for thoracic aortic disease

OBJECTIVE To examine the potential of aortic arch variants, specifically bovine aortic arch, isolated left vertebral artery, and aberrant right subclavian artery, as markers for thoracic aortic disease (TAD). METHODS We screened imaging data of 556 patients undergoing surgery due to TAD for presence of aortic arch variations. Demographic data were collected during chart review and compared with a historical control group of 4617 patients. RESULTS Out of 556 patients with TAD, 33.5% (186 patients) demonstrated anomalies of the aortic arch, compared with 18.2% in the control group (P < .001). Three hundred seventy (66.5%) had no anomaly of the aortic arch. Bovine aortic arch emerged as the most common anomalous branch pattern with a prevalence of 24.6% (n = 137). Thirty-five patients (6.3%) had an isolated left vertebral artery, and 10 patients (1.8%) had an aberrant right subclavian artery. When compared with the control group, all 3 arch variations showed significant higher prevalence in patients with TAD (P < .001). Patients with aortic aneurysms and anomalous branch patterns had hypertension less frequently (73.5% vs 81.8%; P = .048), but had a higher rate of bicuspid aortic valve (40.8% vs 30.6%; P = .042) when compared with patients with aneurysms but normal aortic arch anatomy. Patients with aortic branch variations were significantly younger (58.6 ± 13.7 years vs 62.4 ± 12.9 years; P = .002) and needed intervention for the aortic arch more frequently than patients with normal arch anatomy (46% vs 34.6%; P = .023). CONCLUSIONS Aortic arch variations are significantly more common in patients with TAD than in the general population. Atypical branching variants may warrant consideration as potential anatomic markers for future development of TAD.

Deep Hypothermic Circulatory Arrest Effectively Preserves Neurocognitive Function

BACKGROUND Few (conflicting) studies have quantitatively assessed neurocognitive effects of deep hypothermic circulatory arrest (DHCA). We assess neurocognitive function quantitatively before and after DHCA in comparison with non-DHCA patients. METHODS Sixty-two aortic surgical patients underwent a battery of neuropsychometric tests, both preoperative and postoperative, evaluating multiple aspects of memory, processing speed, executive function, and global cognition. Thirty-three patients did not require DHCA, and 29 underwent DHCA as the sole means of cerebral protection. Neurocognitive deficit was defined as greater than 20% decline in 2 or more cognitive areas. Preoperative and postoperative test scores, as well as incidence of neurocognitive deficit, were compared within each group, and between the non-DHCA and DHCA groups. RESULTS There were no significant differences in the postoperative versus preoperative scores in any cognitive area tested between DHCA and non-DHCA groups. There was also no difference between the 2 groups in incidence of neurocognitive deficit; 13 non-DHCA, 11 DHCA (p = 1.00). In addition, there was no correlation between time under DHCA and incidence of neurocognitive deficit. Within both groups, there was a decline in memory in the areas of acquisition, retention, and delayed recall. Within the DHCA group, recognition was also affected. CONCLUSIONS While cardiac surgery had some effects on memory, overall neurocognitive function was well preserved and not different between DHCA and non-DHCA patients. Time under DHCA up to 40 minutes was also found to be safe neurocognitively. This study provides strong evidence that straight DHCA effectively preserves neurocognitive function.