A giant right atrial myxoma-The growth rate and multi-modality imaging.

A young and healthy woman presented with progressive dyspnea on exertion. An echocardiogram showed a giant right atrial mass. Cardiac CT angiography provided the most accurate estimate for the tumor size, while 2-D echo, 2-D, and 3-D trans-esophageal echo underestimated the dimensions of the cardiac tumor when referenced by the surgical specimen. We also calculated the growth rate of the right atrial myxoma to be at least 1.2 mm per month based on a normal chest CT 54 months before her presentation. Surgical pathology confirmed typical features of cardiac myxoma in the right atrium.

Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.

BACKGROUND: Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia. METHODS AND RESULTS: Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (P<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (P=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (P=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (P=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (P=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (P=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (P=0.002), peNOS (ser1177) (P=0.04), NFkB (P=0.004), and pAkt (thr308) (P=0.001). CONCLUSIONS: Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.

Anti-angiogenic effect of high-dose resveratrol in a swine model of metabolic syndrome.

BACKGROUND: Resveratrol has been reported to induce angiogenesis in ischemic tissue. We hypothesized that high-dose resveratrol would improve native angiogenesis in a swine model of metabolic syndrome and chronic myocardial ischemia. METHODS: Yorkshire swine were fed a normal diet (Control, n = 7), hypercholesterolemic diet (HCD, n = 7), or hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/day orally, HCD-R; n = 7) beginning 1 month prior to surgery. Chronic ischemia was created by placing an ameroid constrictor on the left circumflex coronary artery. After 7 weeks, swine underwent functional MRI, coronary angiography, and serum and heart tissue harvest for analysis. RESULTS: HCD-R animals had lower body mass index (P < .001), total cholesterol (P < .001), low-density lipoprotein (LDL; P < .001), blood glucose levels (P < .001), and systolic blood pressure (P = .03) than HCD animals. There was no difference in regional myocardial function at 7 weeks (P = .25). Coronary angiograms revealed no difference in Rentrop collateral scores (P = .68). Staining for platelet endothelial cell adhesion molecule-1 demonstrated higher capillary density in the Control group (versus HCD and HCD-R; P = .02). Immunoblotting demonstrated decreased expression of the pro-angiogenic protein vascular endothelial (VE)-cadherin (P = .002) and an increase in anti-angiogenic proteins angiostatin (P = .001) and thrombospondin (P = .02) in the HCD and HCD-R groups. Matrix metalloprotease 2 (MMP 2; P = .47) and MMP 9 (P = .12) were not different among groups. CONCLUSION: Supplemental resveratrol positively modified cardiovascular risk factors including body mass index, cholesterol, glucose tolerance, and systolic blood pressure. However, it did not increase native collateral formation in the ischemic myocardium. This may be a result of increased angiostatin and thrombospondin leading to decreased expression of VE-cadherin and other pro-angiogenic factors.

Should aortas in patients with bicuspid aortic valve really be resected at an earlier stage than tricuspid? CON.

Bicuspid aortic valve (BAV)-associated aortopathy is a complex phenomenon, and the current lack of univocal interpretation of its causes and treatment can be ascribed to the multiform nature of its clinical presentation. Although there is strong bias in the literature favoring more aggressive treatment of ascending aortic dilatation in patients with BAV, evidence supporting this opinion is lacking. This review discusses some of the relevant issues relating to causation to facilitate a better analysis of the current recommendations used to guide surgical management, and concludes that treatment should be tailored by individual valvular pathology, clinical phenotype, and relevant comorbidities, using well-documented evidence-based clinical size criteria.

Thoracic Surgery Directors Association Award. What is the optimal management of late-presenting survivors of acute type A aortic dissection?

BACKGROUND: Although type A aortic dissections represent a surgical emergency, some patients present late after the onset of symptoms. Optimal management of this cohort has not been defined. METHODS: Data on 195 patients with type A dissections followed up at a single institution between 1985 and 2005 were collected prospectively. Of these, 93 patients (47.2%) presented 48 hours or later after the initial onset of pain (group A), and the remaining 102 patients underwent immediate operative repair (group B). Median follow-up was 41.8 months (range, 0 to 386 months). RESULTS: Patients in group A were older (68.8 versus 59.3 years, p = 0.0005) and had a higher incidence of coronary artery disease (42.5% versus 14.6%, p < 0.0001), pulmonary disease (26.6% versus 8.4%, p = 0.0023), and congestive heart failure (14.1% versus 1.0%, p = 0.0004). Long-term survival was similar, although group B showed a trend toward improved 30-day mortality (16.5% versus 8.7%, p = 0.1035). Of the 92 patients in group A, 53 (57.6%) eventually underwent operative repair a median of 8.2 days after symptom onset. There was a trend toward improved long-term survival among patients undergoing repair (p = 0.1031). CONCLUSIONS: Initial medical management with interval operative repair of selected patients referred greater than 2 days following an acute type A dissection is a viable option. Delayed repair after optimization of the clinical condition and detailed evaluation of concomitant diseases results in excellent long-term results.

Natural history of ascending aortic aneurysms in the setting of an unreplaced bicuspid aortic valve.

BACKGROUND: Patients with bicuspid aortic valve (BAV) are at risk for valvular disease and ascending aortic aneurysms and dissections. Although others have investigated the need for concomitant repair, the natural history of aortic disease has not been addressed. METHODS: A review of our institutional clinical database identified 514 patients (326 male, 188 female) with unrepaired ascending aortic aneurysms followed from 1985 to 2005. Seventy patients (13.4%) diagnosed with BAV form group A; the remaining 445 patients form group B. Growth rates and risk factors for complications were assessed. RESULTS: Patients in group A had a lower incidence of hypertension (p = 0.0185), carotid artery disease, and stroke (p = 0.0184), and presented at an earlier age (49.0 versus 64.2 years, p < 0.0001). Group A also had a higher rate of aortic growth (0.19 versus 0.13 cm/year, p = 0.0102). The incidence of rupture and dissection were similar. Overall survival was better among patients with BAV (p < 0.0001). Among patients with BAV, those with aortic stenosis had a higher risk of rupture, dissection, or death before operative repair than did those with normally functioning valves (odds ratio 10.475, 95% confidence interval: 1.153 to 95.155). CONCLUSIONS: Aortic stenosis presents a significant added risk for patients with aneurysmal disease in the face of BAV. Despite faster rates of growth, however, patients with BAV have similar rates of aortic rupture, dissection, and death and improved long-term survival. Contributing to this finding may be the lower incidence of comorbidities, the younger age at presentation, and the more attentive follow-up with earlier operative repair.

Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns.

BACKGROUND: We examined the genetic nature and phenotypic features of thoracic aortic aneurysms (TAAs) and dissections in a large cohort of patients. METHODS: Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had Marfan syndrome (MFS). We determined incidence of familial clustering, age at presentation, rate of aneurysm growth, incidence of hypertension, correlation of aneurysm sites among kindred, and pedigree inheritance patterns. RESULTS: An inherited pattern for TAA was present in 21.5% of non-MFS patients. The predominant inheritance pattern was autosomal dominant (76.9%), with varying degrees of penetrance and expressivity. The familial TAA group was significantly younger than the sporadic group (p < 0.0001), but not as young as the MFS group (p < 0.0001) (mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197 probands and kindred with aneurysm, 131 (66.5%) had TAA, 49 (24.9%) had abdominal aortic aneurysm (AAA), and 17 (8.6%) had cerebral or other aneurysms. Ascending aneurysm paired most commonly with ascending, and descending with abdominal. Abdominal aortic aneurysms (AAAs) and hypertension were more often associated with descending than with ascending TAAs (p < 0.001). Aortic growth rate was highest for the familial group (0.21 cm/y), intermediate for the sporadic group (0.16 cm/y), and lowest for the Marfan group (0.1 cm/y; p < 0.01). CONCLUSIONS: TAAs are frequently familial diseases. The predominant mode of inheritance is autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms in relatives may be seen in the thoracic aorta, the abdominal aorta, or the cerebral circulation. Screening of first-order relatives of probands with TAA is essential. Familial TAAs tend to grow at a higher rate, exemplifying a more aggressive clinical entity.

Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms.

BACKGROUND: Optimal operative decision making in thoracic aortic aneurysms requires accurate information on the risk of complications during expectant management. Cumulative and yearly risks of rupture, dissection, and death before operative repair increase with increasing aortic size, but previous work has not addressed the impact of relative aortic size on complication rates. METHODS: Our institutional database contains data on 805 patients followed up serially with thoracic aortic aneurysms. Body surface area information was obtained on 410 patients (257 male, 153 female). We calculated a new measure of relative aortic size, the "aortic size index," and examined its ability to predict complications in these patients. RESULTS: Increasing aortic size index was a significant predictor of increasing rates of rupture (p = 0.0014) as well as the combined endpoint of rupture, death, or dissection (p < 0.0001). Using aortic size index, patients were stratified into three risk groups: less than 2.75 cm/m2 are at low risk (approximately 4% per year), 2.75 to 4.24 cm/m2 are at moderate risk (approximately 8% per year), and those above 4.25 cm/m2 are at high risk (approximately 20% per year). CONCLUSIONS: This study confirms that (1) thoracic aortic aneurysm is a lethal disease, (2) relative aortic size is more important than absolute aortic size in predicting complications, and (3) a novel measurement of relative aortic size allows for the stratification of patients into three levels of risk, enabling appropriate surgical decision-making.

Indications, timing, and prognosis of operative repair of aortic dissections.

Since the first description of aortic dissection in the 1700s, the understanding and treatment of this catastrophic disease has evolved. Aortic dissections are identified as a tear in the aortic intima and inner layer of the media that allows for blood flow within the aortic wall. The area of the vessel involved determines its classification. The classification, in turn, helps to predict outcomes, which allows for appropriate treatment planning. The goal of this article is to outline the operative indications and timing for Stanford type A and type B dissections, based on prior reported data and our own clinical experience with 176 patients treated surgically at the Yale Center for Thoracic Aortic Disease. With this data we will revisit the importance of looking at each patient individually to devise an appropriate operative plan, with the knowledge that treatment for type A dissections is operative and treatment for type B dissections is medical unless patients present with actual or impending rupture, malperfusion, or failure of medical management.

Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms.

BACKGROUND: Progressive medial degeneration and atrophy is thought to be a cause of ascending thoracic aortic aneurysms in the elderly. Extensive apoptosis of vascular smooth muscle cells (VSMCs) has been demonstrated in the media of abdominal aortic aneurysms. We investigated whether medial atrophy from loss of VSMCs occurs in primary ascending thoracic aortic aneurysms. METHODS AND RESULTS: Morphometric analysis of 28 nonaneurysmal ascending thoracic aortas and 29 ascending thoracic aortic aneurysms was performed by directly measuring the thickness of their vascular layers and by indirectly calculating the area of their vascular compartments. The cellular and matrix composition of the media was assessed at the structural, protein, and transcript levels. Despite thinning of the media secondary to vascular dilatation, there was an overall increase in the medial area of aneurysms. VSMC density was preserved, implying cellular hyperplasia as a result of the increased medial mass. There was decreased expression of matrix proteins, despite sustained synthesis of these molecules, which was associated with evidence of increased matrix degradation. The remodeling and expansion of the media was most evident in comparisons between nonaneurysmal aortas versus smaller aneurysms and did not evolve further in larger aneurysms. CONCLUSIONS: The mechanisms for luminal enlargement in thoracic and abdominal aortic aneurysms differ significantly with regard to the survival of VSMCs and atrophy of the media but share common pathophysiology involving degeneration of the matrix. Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms may be an initial adaptive response to minimize increased wall stress resulting from vascular dilatation.

Transmural inflammation by interferon-gamma-producing T cells correlates with outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Arterial pathology manifests as aneurysmal or obstructive disease depending on changes in lumen size due to vascular remodeling (change in vessel external diameter) and/or intimal expansion. Recent clinical and experimental observations in abdominal aortic aneurysms have led to the emerging dogma that Th2-dominant immune responses result in expansive vascular remodeling and luminal ectasia, whereas Th1 immune responses cause intimal hyperplasia and luminal stenosis. We tested this hypothesis by descriptive analyses of 31 non-aneurysmal and 29 aneurysmal ascending thoracic aortic specimens. Approximately half the aneurysms were distinguished by transmural inflammation. The remaining aneurysms and all the non-aneurysmal aortas had a similar leukocytic infiltrate that spared the inner media. Aneurysm tissue had increased expression of the prototypical Th1 cytokine, interferon (IFN)-gamma, and undetectable Th2 cytokines. Specimens with inner media infiltration displayed robust production of IFN-gamma, induction of the IFN-gamma-inducible chemokines IP-10 and Mig, and recruitment of lymphocytes bearing their cognate receptor CXCR3. Transmural inflammation and IFN-gamma production were associated with increased aortic external diameter, intimal thickening, preserved vascular smooth muscle cell density, and decreased matrix proteins. Th1, but not Th2, immune responses have a positive correlation with both outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Femoro-femoral partial bypass in the treatment of thoracoabdominal aneurysms.

This article describes our rationale for the use of femoro-femoral bypass as a primary modality for perfusion in the repair of thoracoabdominal aortic aneurysms at Stanford University School of Medicine. Benefits and limitations of this method are discussed and compared with other described techniques.

Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size.

BACKGROUND: Prior work has clarified the cumulative, lifetime risk of rupture or dissection based on the size of thoracic aneurysms. Ability to estimate simply the yearly rate of rupture or dissection would greatly enhance clinical decision making for specific patients. Calculation of such a rate requires robust data. METHODS: Data on 721 patients (446 male, 275 female; median age, 65.8 years; range, 8 to 95 years) with thoracic aortic disease was prospectively entered into a computerized database over 9 years. Three thousand one hundred fifteen imaging studies were available on these patients. Five hundred seventy met inclusion criteria in terms of length of follow-up and form the basis for the survival analysis. Three hundred four patients were dissection-free at presentation; their natural history was followed for rupture, dissection, and death. Patients were excluded from analysis once operation occurred. RESULTS: Five-year survival in patients not operated on was 54% at 5 years. Ninety-two hard end points were realized in serial follow-up, including 55 deaths, 13 ruptures, and 24 dissections. Aortic size was a very strong predictor of rupture, dissection, and mortality. For aneurysms greater than 6 cm in diameter, rupture occurred at 3.7% per year, rupture or dissection at 6.9% per year, death at 11.8%, and death, rupture, or dissection at 15.6% per year. At size greater than 6.0 cm, the odds ratio for rupture was increased 27-fold (p = 0.0023). The aorta grew at a mean of 0.10 cm per year. Elective, preemptive surgical repair restored life expectancy to normal. CONCLUSIONS: This study indicates that (1) thoracic aneurysm is a lethal disease; (2) aneurysm size has a profound impact on rupture, dissection, and death; (3) for counseling purposes, the patient with an aneurysm exceeding 6 cm can expect a yearly rate of rupture or dissection of at least 6.9% and a death rate of 11.8%; and (4) elective surgical repair restores survival to near normal. This analysis strongly supports careful radiologic follow-up and elective, preemptive surgical intervention for the otherwise lethal condition of large thoracic aortic aneurysm.