Leonard N. Girardi

Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+AC133+ Endothelial Precursor Cells

Abstract — Bone marrow (BM)–derived circulating endothelial precursor cells (CEPs) are thought to play a role in postnatal angiogenesis. Emerging evidence suggests that angiogenic stress of vascular trauma may induce mobilization of CEPs to the peripheral circulation. In this regard, we studied the kinetics of CEP mobilization in two groups of patients who experienced acute vascular insult secondary to burns or coronary artery bypass grafting (CABG). In both burn and CABG patients, there was a consistent, rapid increase in the number of CEPs, determined by their surface expression pattern of vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial cadherin (VE-cadherin), and AC133. Within the first 6 to 12 hours after injury, the percentage of CEPs in the peripheral blood of burn or CABG patients increased almost 50-fold, returning to basal levels within 48 to 72 hours. Mobilized cells also formed late-outgrowth endothelial colonies (CFU-ECs) in culture, indicating that a small, but significant, number of circulating endothelial cells were BM-derived CEPs. In parallel to the mobilization of CEPs, there was also a rapid elevation of VEGF plasma levels. Maximum VEGF levels were detected within 6 to 12 hours of vascular trauma and decreased to baseline levels after 48 to 72 hours. Acute elevation of VEGF in the mice plasma resulted in a similar kinetics of mobilization of VEGFR2+ cells. On the basis of these results, we propose that vascular trauma may induce release of chemokines, such as VEGF, that promotes rapid mobilization of CEPs to the peripheral circulation. Strategies to improve the mobilization and incorporation of CEPs may contribute to the acceleration of vascularization of the injured vascular tissue.

Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.

En bloc esophagectomy improves survival for stage III esophageal cancer.

OBJECTIVE The role of en bloc esophagectomy in the surgical treatment of patients with locally advanced esophageal cancer is not well defined. This report attempts to elucidate its impact on survival, in comparison with less extensive resection, among patients with stage III disease. METHODS A prospectively established database was retrospectively analyzed. RESULTS One hundred twenty-eight patients underwent esophagectomy for carcinoma of the thoracic esophagus between 1988 and 1996 (78 underwent en bloc resection and 50 underwent standard resection). The 30-day and hospital mortality rates were 3.9% and 5.4%, respectively, comparable for the two procedures. Fifty-four patients had stage III disease. Overall 4-year survival was 34.5% after en bloc resection, with a median survival of 27 months (n = 33), and 11% after standard resection (n = 21), with a median survival of 12 months (p = 0.007). Among patients with stage III disease undergoing a complete resection, 4-year survivals were 36.7% and 0% after en bloc and standard resections, respectively (p = 0.001). Eighty-six of 128 patients had nodal metastasis. Three-year survivals for patients with NI disease were 33.9% and 13% after en bloc and standard resections, respectively (p = 0.02). CONCLUSION Among patients with stage III esophageal cancer, en bloc resection appears to significantly improve survival compared with lesser resections. This improvement in survival may be attributable to resection of nodal disease.

Pericardiocentesis and Intrapericardial Sclerosis: Effective Therapy for Malignant Pericardial Effusions

BACKGROUND Pericardial effusions remain a formidable problem in patients with an advanced malignancy. We reviewed our experience with pericardiocentesis and intrapericardial sclerotherapy versus open surgical drainage as the treatment for these effusions. METHODS A retrospective review was performed of one surgeons experience (M.E.B.) with the surgical treatment of malignant pericardial effusions at a tertiary-care cancer center. RESULTS Sixty patients underwent 72 procedures during 8 years. Thirty-seven (51%) pericardiocenteses and 35 (49%) open procedures were performed in patients with effusions. There was no significant difference in the complication rates seen between those effusions drained via pericardiocentesis (n = 5; 13%) and those drained in an open surgical procedure (n = 5; 14%). Similar results were seen with respect to the development of a recurrent effusion. There were no procedure-related deaths. The median survival for all patients was 97 days. Patients with breast cancer as their primary malignancy survived significantly longer after drainage than did all others (p = 0.01). The type of procedure did not influence survival. Costs of surgical drainage exceed those of pericardiocentesis by nearly fortyfold. CONCLUSIONS Pericardiocentesis with intrapericardial sclerotherapy is as effective as open surgical drainage for the management of malignant pericardial effusions.

Outcomes of cardiac surgery in nonagenarians: a 10-year experience

BACKGROUND With an increasing awareness of health issues and greater emphasis on preventive medicine, the general population is living longer and healthier lives than ever before. Physicians are taking care of older patients, many of whom may require cardiac surgical procedures. Improving cardiopulmonary bypass technology allows for safer procedures with reduced morbidity and mortality even in older patients. METHODS We have performed a retrospective analysis of 42 consecutive nonagenarian patients who underwent open-heart procedures over a 10-year period (1993 to 2002) at our institution. Their demographic profiles, operative data, perioperative results, and long-term outcomes were recorded and analyzed. RESULTS Twenty-two women and 20 men with an age range of 90 to 97 years (mean, 91.4 years) had open-heart surgery over the study period. The complication rate was 67% overall, consisting of 7% respiratory (pneumonia, respiratory failure, reintubation), 7% hemorrhagic or embolic (postoperative bleeding, cerebral vascular accident), 12% infectious (wound infection, sepsis), and 31% new arrhythmia (atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation). Despite these complication rates, average hospital stay was 17.5 days (median, 11 days), with an intensive care unit stay of 12.0 days (median, 5 days). Thirty-day survival was 95% and survival to discharge was 93% (three deaths total; one cardiac arrest at hospital day 134 and two perioperative deaths; one ventricular arrhythmia, one cerebral vascular accident). The only statistically significant risk factor of mortality was emergency surgery. Currently, 81% are still alive an average of 2.53 years since surgery (range, 0.16 to 7.1 years). CONCLUSIONS With improving techniques and greater attention to detail, the select nonagenarian can safely undergo cardiac surgery.

Surgical treatment of atrial fibrillation using argon-based cryoablation during concomitant cardiac procedures.

Background—The development of ablative energy sources has simplified the surgical treatment of atrial fibrillation (AF) during concomitant cardiac procedures. We report our results using argon-based endocardial cryoablation for the treatment of AF in patients undergoing concomitant cardiac procedures. Methods and Results—Sixty-three patients with AF who were undergoing concomitant cardiac procedures had the same left atrial endocardial lesion set using a flexible argon-based cryoablative device. Mean age was 65.1±1.3 years. Sixty-two percent had permanent AF, whereas 38% had paroxysmal AF. Mean duration of AF was 30.5±4.8 months. Mean left atrial diameter was 5.5±0.1 cm. Mean ejection fraction was 45±1.4%. All endocardial lesions were performed for 1 minute once tissue temperature reached −40°C. Follow-up echocardiograms were obtained to determine freedom from AF. Kaplan-Meier analysis demonstrated an 88.5% freedom from AF rate at 12 months. Ablation time was 16.8±0.6 minutes. There were no in-hospital deaths and no strokes. Twelve patients (19%) required postoperative permanent pacemaker placement. Conclusions—Cryoablation using this flexible argon-based device for the treatment of AF during concomitant cardiac procedures was safe and effective, with 88.5% of patients free from AF at 12 months.

Ruptured descending and thoracoabdominal aortic aneurysms

BACKGROUND Advances in end-organ protection have dramatically reduced the incidence of the life-threatening complications associated with the elective repair of thoracoabdominal and descending thoracic aortic aneurysms. However, in the setting of a ruptured thoracic aneurysm, one may not have the luxury of complex end-organ support. We analyzed our experience with ruptured thoracic aneurysms to define morbidity and mortality in the present era. METHODS One hundred seventy-two patients with thoracoabdominal or descending thoracic aneurysms were operated on between July 1997 and October 2001. Forty presented with either a contained or free rupture. Three techniques were used for aortic reconstruction: clamp and sew, left heart bypass, and hypothermic circulatory arrest. Adjuncts for neurologic and renal support were used when circumstances and anatomy permitted. RESULTS Seven of 40 patients died in the hospital (17.5%). Four patients died intraoperatively, all of acute myocardial infarction. Five of the seven deaths were in patients who presented in shock. Two patients (5%) experienced paraplegia, 3 (7.5%) had renal failure requiring hemodialysis, 8 (20%) required a tracheostomy, and 6 (15%) had recurrent nerve palsies. There was one stroke (2.6%). Mean diameter of ruptured aneurysms was 8.5 cm. CONCLUSIONS Ruptured thoracic aneurysms can be repaired with a gratifying rate of salvage. Rapid diagnosis and triage for repair is necessary to avoid progressive deterioration into shock. The incidence of myocardial infarction, and the mortality associated with this event, underscores the need for aggressive cardiac evaluation in the elective thoracic aneurysm patient. The size at rupture also emphasizes the need for earlier referral for elective aneurysm repair.

Inflammatory Aneurysm of the Ascending Aorta and Aortic Arch

Inflammatory aortic aneurysms are distinct clinical entities seen mostly in the infrarenal abdominal aorta and rarely in the descending thoracic aorta. We present the case of a 61-year-old woman with an inflammatory aortic aneurysm of the ascending aorta and aortic arch.

Recurrent systemic embolization caused by aortic thrombi

The aorta is a commonly unrecognized source of systemic embolization. Transesophageal echocardiography is a reliable method for visualization of the intima of the thoracic aorta and identification of aortic thrombi. Balloon embolectomy of the aorta can be used to remove thrombi and prevent further embolic events.

Acceptability and psychometric properties of the Minnesota Living With Heart Failure Questionnaire among patients undergoing heart valve surgery: validation and comparison with SF-36.

BACKGROUND Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS. METHODS AND RESULTS We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbachs alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002). CONCLUSIONS Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.