The influence of operative techniques on the outcomes of bicuspid aortic valve disease and aortic dilatation.

BACKGROUND: Bicuspid aortic valve is associated with aortic aneurysm formation that may extend beyond the ascending aorta. METHODS: Between 1979 and 1997, 143 bicuspid aortic valve patients had aortic valve operations with replacement of an aneurysmal ascending aorta: 93 (65%) underwent full root replacement and 50 (35%) underwent separate valve and graft replacement. Distal aortic anastomosis was open in 42 patients (29%) and closed in 101 (71%). Late survival and complications were compared by surgical technique. RESULTS: Patients undergoing full root replacement tended to be younger (mean age 46 +/- 16 vs 59 +/- 13, p < 0.001) and presented with more aortic insufficiency (80% vs 35%, p < 0.001). Three (2.1%) hospital deaths occurred. Event-free survival was 82% (95% confidence interval, 75% to 88%) at 10 years and 41% (95% confidence interval, 11% to 71%) at 20 years. At a median follow-up of 11.5 years, the incidence of new aneurysms and late aortic complications were not significantly different among the procedure groups. Age at the time of operation was the only predictor of late survival (hazard ratio, 1.07; p = 0.007). CONCLUSIONS: Aortic root replacement with distal aortic reconstruction can be achieved with very low operative mortality and excellent long-term outcomes in patients with bicuspid aortic valve and dilated ascending aorta. The type of surgical procedure done in the aortic root and in the distal ascending aorta does not influence late survival, subsequent operation, or aortic complications. This is likely influenced by our patient-specific strategy when replacing the aortic root and distal ascending aorta.

Improvement in cardiac function after bone marrow cell thearpy is associated with an increase in myocardial inflammation.

The mechanisms for the beneficial impact of bone marrow cell (BMC) therapy after myocardial infarction (MI) are ill defined. We hypothesized that the implanted cells improve function by attenuating post-MI inflammation and repair. In mice, 3 x 10(5) fresh BMCs were implanted immediately after coronary ligation. Cardiac function was evaluated over time. Inflammatory cytokines and cells were measured, and their impacts on the (myo)fibroblastic repair response, angiogenesis, and scar formation were determined. All differences below had P values of <0.05. BMC implantation reduced the decline in fractional shortening and ventricular dilation. Invasive hemodynamics confirmed a difference in systolic function at day 7 and diastolic function at day 28 favoring the BMC group. Interestingly, BMC implantation caused a 1.6-fold increase in the number of macrophages infiltrating the infarct but did not affect neutrophils. This increase was associated with a 1.9-fold higher myocardial TNF-alpha level. The heightened inflammatory response was associated with a 1.4-fold induction of transforming growth factor-beta and a 1.3-fold induction of basic fibroblast growth factor. These changes resulted in a 1.6-fold increase in alpha-smooth muscle actin and a 1.9-fold increase in total discoidin domain receptor 2-expressing cells in the BMC group. These two markers are expressed by cardiac (myo)fibroblasts. Capillary density in the border zone increased 2.0-fold. Consistent with a more robust repair-mediated scar "contracture," the final scar size was 0.7-fold smaller in the BMC group. In conclusion, after MI, BMC therapy induced a more robust inflammatory response that improved the "priming" of the (myo)fibroblast repair phase. Enhancing this response may further improve the beneficial impact of cellular therapy.

The aortopathy of bicuspid aortic valve disease has distinctive patterns and usually involves the transverse aortic arch.

OBJECTIVES: Bicuspid aortic valves are associated with a poorly characterized connective tissue disorder that predisposes to aortic catastrophes. Because no criterion exists dictating the appropriate extent of aortic resection in aneurysmal disease of the bicuspid aortic valve, we studied the patterns of aortic dilation in this population. METHODS: Sixty-four patients with bicuspid aortic valves who underwent computed tomographic or magnetic resonance angiography and echocardiography were retrospectively identified between January 2002 and March 2006. Orthonormal 2-dimensional or 3-dimensional aortic diameters were measured at 10 levels. Agglomerative hierarchic clustering with centered correlation distance measurements and complete linkage analysis was used to detect distinct patterns of aortic dilatation. RESULTS: Mean aortic diameter was 28.1 +/- 0.7 mm at the annulus and 21.7 +/- 0.4 mm at the diaphragmatic hiatus. The aorta was largest in the tubular ascending aorta (45.9 +/- 1.0 mm). Compared with the descending aorta, the transverse aortic arch was also dilated (P < .01). Cluster analysis showed 4 patterns of aortic dilatation: cluster I, aortic root alone (n = 8, 13%); cluster II, tubular ascending aorta alone (n = 9, 14%); cluster III, tubular portion and transverse arch (n = 18, 28%); and, cluster IV, aortic root and tubular portion with tapering across the transverse arch (n = 29, 45%). CONCLUSION: Distinct patterns of aortic dilatation in patients with bicuspid aortic valves call for an individualized degree of aortic replacement to minimize late aortic complications and reoperation. Patients in clusters III and IV should have transverse arch replacement (plus concomitant root replacement in cluster IV). Patients in cluster I should undergo complete aortic root replacement, whereas in patients in cluster II supracommissural ascending aortic grafting is adequate.

Activation of c-kit is necessary for mobilization of reparative bone marrow progenitor cells in response to cardiac injury.

Cardiovascular disease is the number-one cause of mortality in the developed world. The aim of this study is to define the mechanisms by which bone marrow progenitor cells are mobilized in response to cardiac ischemic injury. We used a closed-chest model of murine cardiac infarction/reperfusion, which segregated the surgical thoracotomy from the induction of cardiac infarction, so that we could study isolated fluctuations in cytokines without the confounding impact of surgery. We show here that bone marrow activation of the c-kit tyrosine kinase receptor in response to released soluble KitL is necessary for bone marrow progenitor cell mobilization after ischemic cardiac injury. We also show that release of KitL and c-kit activation require the activity of matrix metalloproteinase-9 within the bone marrow compartment. Finally, we demonstrate that mice with c-kit dysfunction develop cardiac failure after myocardial infarction and that bone marrow transplantation rescues the failing cardiac phenotype. In light of the ongoing trials of progenitor cell therapy for heart disease, our study outlines the endogenous repair mechanisms that are invoked after cardiac injury. Amplification of this pathway may aid in restoration of cardiac function after myocardial infarction.

Aortic valve-sparing operations for aortic root and ascending aortic aneurysms.

PURPOSE OF REVIEW: Techniques of aortic root replacement have been developed that preserve the native aortic valve. These techniques avoid anticoagulation in patients who would otherwise receive a composite valve graft with a mechanical valve. RECENT FINDINGS: Longer-term data on the longevity of the main two techniques of aortic valve-sparing operations, the root remodeling and the valve reimplantation technique, are now becoming available. Root remodeling appears to have acceptable outcomes in patients without annuloaortic ectasia or Marfan syndrome. In such patients, the aortic valve reimplantation technique provides superior longevity because it provides external support for the aortic annulus and prevents ongoing dilatation. SUMMARY: Although aortic valve-sparing operations are being performed more frequently, particularly in younger patient populations, these procedures have not been adopted in the current guidelines. The excellent long-term outcomes of such procedures should facilitate their widespread adoption.