David P. Franklin

Dobutamine stress echocardiography for cardiac risk assessment before aortic surgery

PURPOSEnThis study evaluates dobutamine stress echocardiography (DSE) for perioperative cardiac risk assessment with elective aortic surgery.nnnMETHODSnDobutamine stress echocardiography was used to evaluate 81 patients before infrarenal aortic surgery. Patients were placed into three groups. Group I (n = 31) had normal DSEs. Group II (n = 25) had resting wall motion abnormalities without dobutamine-induced changes of ischemia. Group III (n = 25) had evidence of dobutamine-induced ischemia. Patient analysis revealed that of 46 patients with clinical indicators of coronary artery disease (CAD), only 23 had DSEs with inducible ischemia. Two of 35 patients without clinical indicators of CAD had DSEs with inducible ischemia.nnnRESULTSnThe 56 patients in group I and II underwent aortic reconstruction without cardiac complications or death. Of the 25 patients in group III, surgery was deferred in five (two patients with claudication and three with aneurysms < or = 5 cm), and four underwent coronary artery bypass grafting. Outcome after coronary artery bypass grafting included one death from stroke, one aneurysm rupture, and two uncomplicated aortic reconstructions. The remaining 16 patients in group III underwent aortic surgery, with three postoperative myocardial infarctions (MI) and no deaths.nnnCONCLUSIONSnUsing DSE for preoperative assessment of cardiac risk allowed us to operate on 74 of 81 patients being considered for elective aortic reconstruction, with no operative deaths and a 4.1% rate of perioperative MI. Dobutamine stress echocardiography has the ability to identify patients with asymptomatic stress-induced ischemic myocardium and its increased risk for perioperative MI (p < 0.001). Equally important, for patients with clinical indicators of CAD but without DSE-inducible ischemia, no further cardiac evaluation is necessary.

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association

OBJECTIVEnThe goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs).nnnMETHODSnA genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set.nnnRESULTSnA genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site.nnnCONCLUSIONnThis study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

Aberrant right subclavian artery: Varied presentations and management options

Although an aberrant right subclavian artery arising from the proximal portion of the descending thoracic aorta is the most common aortic arch anomaly, few patients have clinical symptoms directly attributable to it. When symptoms do occur they are usually causally related to aneurysmal or occlusive sequelae of atherosclerotic disease of the anomalous vessel. More unusual manifestations peculiar to the anomalous artery include aneurysmal degeneration of the origin of the vessel from the aortic arch, with its inherent risk of rupture, or symptoms of compression of the trachea or more commonly the esophagus by the anomalous vessel as it traverses the superior mediastinum. In patients with symptoms a variety of operative approaches and management strategies have been used. Our recent experience with treatment of two patients with clinical symptoms caused by an aberrant right subclavian artery illustrate the varied surgical options and prompted a review of the surgical management of this unusual anomaly.

Carotid duplex overestimation of stenosis due to severe contralateral disease

BACKGROUNDnIn the quest to use carotid duplex to assess carotid occlusive disease, it has been reported that the current velocity criteria to calculate stenosis tends to overestimate the severity when there is a contralateral highly stenotic or occluded carotid artery.nnnMETHODSnPatient records were reviewed for 592 consecutive carotid endarterectomies performed from 1987 to 1994. Preoperative and postoperative duplex scan results were compared in a subset of patients in whom duplex overestimated the degree of stenosis, as compared to preoperative angiography.nnnRESULTSnA total of 146 patients were identified in whom duplex overestimated the degree of stenosis contralateral to a high grade stenosis or an occlusion. Of 76 arteries, 18 (23.7%) contralateral to an occluded artery were overestimated by duplex, and 128 (27.0%) of 474 arteries contralateral to a high grade stenosis were overestimated. Following endarterectomy 44 (51.8%) of 128 nonoperated contralateral stenoses decreased by at least one duplex category. The average peak systolic frequency (PSF) decreased by 1175 Hz (P = 0.0018), and the average end diastolic frequency (EDF) decreased by 475 Hz (P = 0.011).nnnCONCLUSIONSnPatients with high grade stenosis have a significant decrease in PSF and EDF in the unoperated carotid after endarterectomy, supporting a compensatory flow phenomenon. This often results in a decrease in the postoperative duplex defined stenosis by at least one category. The clinical significance of these findings is of increasing importance as carotid surgery is being performed more frequently without angiography.

MicroRNA expression signature in human abdominal aortic aneurysms

BackgroundAbdominal aortic aneurysm (AAA) is a dilatation of the aorta affecting most frequently elderly men. Histologically AAAs are characterized by inflammation, vascular smooth muscle cell apoptosis, and extracellular matrix degradation. The mechanisms of AAA formation, progression, and rupture are currently poorly understood. A previous mRNA expression study revealed a large number of differentially expressed genes between AAA and non-aneurysmal control aortas. MicroRNAs (miRNAs), small non-coding RNAs that are post-transcriptional regulators of gene expression, could provide a mechanism for the differential expression of genes in AAA.MethodsTo determine differences in miRNA levels between AAA (nu2009=u20095) and control (nu2009=u20095) infrarenal aortic tissues, a microarray study was carried out. Results were adjusted using Benjamini-Hochberg correction (adjusted pu2009<u20090.05). Real-time quantitative RT-PCR (qRT-PCR) assays with an independent set of 36 AAA and seven control tissues were used for validation. Potential gene targets were retrieved from miRNA target prediction databases Pictar, TargetScan, and MiRTarget2. Networks from the target gene set were generated and examined using the network analysis programs, CytoScape® and Ingenuity Pathway Core Analysis®.ResultsA microarray study identified eight miRNAs with significantly different expression levels between AAA and controls (adjusted pu2009<u20090.05). Real-time qRT-PCR assays validated the findings for five of the eight miRNAs. A total of 222 predicted miRNA target genes known to be differentially expressed in AAA based on a prior mRNA microarray study were identified. Bioinformatic analyses revealed that several target genes are involved in apoptosis and activation of T cells.ConclusionsOur genome-wide approach revealed several differentially expressed miRNAs in human AAA tissue suggesting that miRNAs play a role in AAA pathogenesis.

Ruptured abdominal aortic aneurysm repair: The financial analysis

BACKGROUNDnDenial of ruptured abdominal aortic aneurysm (RAAA) repair has been advocated based upon historically poor surgical outcome and a perceived lack of cost effectiveness. Although the repair intuitively seems expensive, the actual cost of care, adequacy of reimbursement, and cost per additional life-year gained for RAAA repair are poorly defined.nnnPATIENTS AND METHODSnRetrospective clinical and financial chart review of 119 consecutive patients undergoing operation for RAAA from 1986 to 1993.nnnRESULTSnOverall in-hospital mortality was 45%. Mean institutional charge per patient in 1993 dollars was

Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms

40,763 (range

Novel pathways in the pathobiology of human abdominal aortic aneurysms

4,473 to

Role of Complement Cascade in Abdominal Aortic Aneurysms

284,374), with an actual mean cost for service of

Ultrasound-Guided Thrombin Injection Is a Safe and Durable Treatment for Femoral Pseudoaneurysms

22,420 and an average reimbursement of