Disparities in Outcomes Between Sexes in Type B Aortic Dissection Patients Treated with TEVAR.

BACKGROUND: To evaluate differences in presentation and outcomes between sexes in patients who underwent thoracic endovascular aortic repair for type B aortic dissection (TBAD). METHODS: Between January 1, 2012 and January 1, 2017 186 patients underwent thoracic endovascular aortic repair for TBAD at a single institution. Men (n = 112) and women (n = 74) were compared based on presenting demographics, comorbidities, and postoperative complications. Primary outcomes were survival and need for reintervention. RESULTS: Women were older (P = 0.04) and had a lower body mass index (P = 0.03). More women (F) presented with continued pain or refractory hypertension (51.0% F, 30.0% M), while more men (M) presented with acute complicated dissections (19.0% F, 39.0% M) (P = 0.008). At presentation, women had statistically higher relative rates of chronic obstructive pulmonary disease (P = 0.05), hyperlipidemia (P = 0.03), and smoking (P = 0.03). Significantly more women were on Medicare without Medicaid (55.0% F, 34.0% M), while men had private insurance (35.0% F, 13.0% M) (P = 0.005). There was no significant difference in blood pressure control at presentation, discharge, or at 30 days. When normalized by body surface area, women had larger ascending aortic diameters (19.2(3.10)F, 17.5(2.40)M, P = 0.0002), as well as proportionally larger true lumens at the left subclavian artery (14.9(2.90)F, 13.4(2.50)M, P = 0.0002), carina (12.6(5.80)F, 9.90(4.80)M, P = 0.0009), and celiac (10.5(4.50)F, 8.50(4.10)M, P = 0.006) levels, and at the largest point of dissection (11.6(6.50)F, 9.60(4.80)M, P = 0.04), as well as proportionately smaller false lumens at the carina (5.90(5.60)F, 9.30(6.10)M, P = 0.003). Despite not being statistically significant, women had lower rates of stroke (6.80% F, 8.00% M, P = 0.7) and acute kidney injury (5.40% F, 11.6% M, P = 0.2), as well fewer days in the intensive care unit (ICU) (3.20(4.30)F, 4.60(6.60)M, P = 0.2) and an overall shorter length of stay (6.80(6.70)F, 8.00(8.20)M, P = 0.5). Kaplan-Meier estimates for survival for women versus men were 96.0% vs. 92.0%, 90.0% vs. 79.0%, and 70.0% vs. 69.0% at 30 days, 1 year, and 3 years, respectively (P = 0.042). Kaplan-Meier estimates for freedom from reintervention for women versus men were 89.0% vs. 90.0%, 58.0% vs. 72.0%, and 48.0% vs. 58.0% at 30 days, 1 year, and 3 years, respectively (P = 0.13). CONCLUSIONS: Women present with TBAD at an older age, have more comorbidities, lower socioeconomic status, and have larger ascending aortic diameters for their size. Despite having less severe dissections as evidenced by smaller false lumens and wider true lumens, it does not appear that this correlates with improved outcomes for women when compared to men. It appears that this is one of the few, if not only, aortic pathologies that result in comparable outcomes between sexes.

Thoracic Stent Grafts Induce Persistent Aortic Remodeling in Aortic Coarctation.

BACKGROUND: This study's objective is to describe outcomes of adult patients who underwent thoracic stent graft placement treatment for primary or recurrent aortic coarctation. METHODS: This is a retrospective study of 30 adult patients who underwent thoracic stent graft placement for aortic coarctation at our institution. Average age was 46.5 years, with 53.3% of patients presented with no prior treatment or repair for coarctation. Indications for repair included gradient ≥20 mm Hg with anatomic evidence of coarctation on imaging with left ventricular hypertrophy, pseudoaneurysm, aneurysm, refractory hypertension, or claudication. Stent grafts used for repair included MDT (Medtronic, Santa Rosa, CA) and GORE TAG (W. L. Gore & Associates, Flagstaff, AZ). RESULTS: Patients were observed for a median of 979 days, with one death during the study. All patients had complete resolution of symptoms with no recurrences. Thoracic endovascular aortic repair significantly reduced the gradient across the coarctation (P < 0.0001). Aortic coarctation diameter significantly increased at 30 days postoperatively and continued to increase up to 5 years posttreatment. At 3+ years, aortic remodeling was observed at the coarctation site and surrounding regions. At 30 days, systolic, diastolic, and mean arterial pressure were all reduced. Systolic and diastolic blood pressure and mean arterial pressure continued to significantly improve 1-year posttreatment. CONCLUSIONS: Stent grafts are a safe and effective treatment for aortic coarctation. We observed a clinically significant improvement in blood pressure and longitudinal aortic remodeling of the coarctation segment and the entire aorta that persisted more than more than 3 years.

Cocaine use is associated with worse outcomes in patients treated with thoracic endovascular repair for type B aortic dissection.

OBJECTIVE: To describe and compare the clinical and anatomical characteristics and outcomes of patients with and without known cocaine use who underwent thoracic endovascular repair for type B aortic dissections. METHODS: Between January 2012 and January 2017, 186 patients underwent thoracic endovascular repair for type B aortic dissection at our institution. Clinical data and anatomical characteristics were collected under an institutional review board-approved protocol. Survival, reintervention, complications, and characteristics of dissection were compared between patients with cocaine use (C+; n = 14) and those with no known cocaine use (C-; n = 172). RESULTS: Cocaine users were more likely to be young African American males who smoked. They tended to present with more extensive dissections as evidenced by larger false lumen diameters. They also had higher rates of endoleaks and more reinterventions. CONCLUSIONS: These results suggest that special care should be taken to provide close follow-up for these patients.

Retrograde type A dissection after thoracic endovascular aortic repair for type B aortic dissection.

BACKGROUND: The purpose of this study was to evaluate clinical, anatomic, and procedural characteristics of patients who developed retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: Between January 2012 and January 2017, there were 186 patients who underwent TEVAR for TBAD at a multidisciplinary aortic center. Patients who developed RTAD after TEVAR (n = 15) were compared with those who did not (no-RTAD group, n = 171). Primary outcomes were survival and need for reintervention. RESULTS: The incidence of RTAD in our sample was 8% (n = 15). Kaplan-Meier estimates found that no-RTAD patients had better survival (P = .04). Survival rates at 30 days, 1 year, and 3 years were 93%, 60%, and 60% for RTAD patients and 94%, 87%, and 80% for no-RTAD patients. One RTAD was diagnosed intraoperatively, 5 were diagnosed within 30 days of the index procedure, 6 were diagnosed within 1 year, and 3 were diagnosed after 1 year. Reintervention for RTAD was undertaken in 10 of 15 patients, with a 50% survival rate after reintervention. Partial or complete false lumen thrombosis was more frequently present in RTAD patients (P = .03). RTAD patients more frequently presented with renal ischemia (P = .04). Most RTAD patients (93%, RTAD patients; 64%, no-RTAD patients; P = .02) had a proximal landing zone in zone 0, 1, or 2. Aortic diameter was more frequently ≥40 mm in the RTAD group (47%, RTAD patients; 21%, no-RTAD patients; P = .05). Patients with RTAD had stent grafts placed in the renovisceral arteries for complicated dissections, and this approached significance (P = .05). Three RTAD patients had a type II arch (20%) compared with 53 no-RTAD patients (31%; P = .6), but a comparison of type II arch with type I or type III found no statistical significance (P = .6). No correlations were found between ratio of descending to ascending diameters, average aortic sizing, graft size, or bare-metal struts at proximal attachment zone and development of RTAD. We found no statistically significant differences in demographics, genetic disease, comorbidities, or previous repairs. CONCLUSIONS: The development of RTAD after TEVAR for TBAD does not appear to be correlated with any easily identifiable demographic feature but appears to be correlated with proximal landing zones in zone 1 and 2 and an ascending diameter >4 cm. Furthermore, the presence of partial or complete false lumen thrombosis as well as more complicated presentation with renal ischemia was significantly more frequent in patients with RTAD. TBAD patients should be observed long term, as type A dissections in our patients occurred even after 1 year.

Ethnic disparities in outcomes of patients with complicated type B aortic dissection.

OBJECTIVE: The objective of this study was to evaluate the difference in outcomes after endovascular intervention in patients with complicated type B aortic dissection (TBAD) based on ethnicity and blood pressure control. METHODS: Between 2012 and 2016, there were 126 patients who underwent endovascular procedures for complicated TBAD at a single-institution quaternary referral center. Patients self-identified as African American (n = 53), white (n = 70), and Asian (n = 3). African American and white patients were compared on a number of variables, including age, ethnicity, insurance type, blood pressure, comorbidities, number of previous interventions, and number of antihypertension medications they were taking before intervention. Primary outcomes were survival and need for reintervention. RESULTS: Kaplan-Meier estimates for survival for African Americans vs whites were 94% vs 89%, 91% vs 83%, 89% vs 79%, and 89% vs 76% at 30 days, 1 year, 3 years, and 5 years, respectively (P = .05). African Americans were younger overall (52.5 ± 11 years) vs whites (63.7 ± 14.7 years; P < .0001). African Americans required a significantly greater number of reinterventions (P = .007). They also had higher rates of chronic kidney disease (P = .01), smoking (P = .03), and cocaine use (P = .02) and were more likely to be on Medicaid (P = .02). Hypertension was poorly controlled in both groups, with the percentage of patients with uncontrolled hypertension (systolic >140 mm Hg) preoperatively, postoperatively, and 30 days after intervention at 32%, 32%, and 39%. There was no significant difference between the cohorts in uncontrolled hypertension preoperatively (P = .39) or postoperatively (P = .63). However, more African Americans had uncontrolled hypertension at 30 days (African Americans, 49%; whites, 31%; odds ratio, 2.1; P = .09). African Americans were taking a greater number of antihypertension medications at presentation than whites (P = .01) and specifically had higher use rates of beta blockers (P = .02), diuretics (P = .02), and angiotensin-converting enzyme inhibitors (P = .04). CONCLUSIONS: African Americans with TBAD present at a younger age than their white counterparts do and have a survival advantage up to at least 5 years. However, African Americans have a higher rate of reintervention that is probably associated with poor blood pressure control despite taking more antihypertension medications both before and after the repair. It appears that optimal medical therapy is difficult to achieve in all groups. More aggressive medical management is needed, particularly more so in African Americans, which may in turn decrease the number of interventions and potentially improve long-term survival.

Normalization of postinfarct biomechanics using a novel tissue-engineered angiogenic construct.

BACKGROUND: Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics. METHODS AND RESULTS: EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01). CONCLUSIONS: We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.

Atrial Cannulation During Resuscitative Clamshell Thoracotomy.

BACKGROUND: Resuscitative thoracotomy and clamshell thoracotomy are performed in the setting of traumatic arrest with the intent of controlling hemorrhage, relieving tamponade, and providing open chest cardiopulmonary resuscitation. Historically, return of spontaneous circulation rates for penetrating traumatic arrest as well as out of hospital survival have been reported as low as 40% and 10%. Vascular access can be challenging in patients who have undergone a traumatic arrest and can be a limiting step to effective resuscitation. Atrial cannulation is a well-established surgical technique in cardiac surgery. Herein, we present a case series detailing our application of this technique in the context of acute trauma resuscitation during clamshell thoracotomy for traumatic arrest in the emergency department. METHODS: A retrospective case series of atrial cannulation during traumatic arrest was conducted in Charlotte, NC at Carolinas Medical Center an urban level 1 trauma center. RESULTS: The mean rate of return of spontaneous circulation in our series, 60%, was greater than previously published upper limit of return of spontaneous circulation for penetrating causes of traumatic arrest. DISCUSSION: Intravenous access can be difficult to establish in the hypovolemic and exsanguinating patient. Traditional methods of vascular access may be insufficient in the setting of central vascular injury. Atrial appendage cannulation during atrial cannulation is a quick and reliable technique to achieve vascular access that employs common methods from cardiac surgery to improve resuscitation of traumatic arrest.

Computational protein design to reengineer stromal cell-derived factor-1α generates an effective and translatable angiogenic polypeptide analog.

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.

Stromal cell-derived factor-1alpha activation of tissue-engineered endothelial progenitor cell matrix enhances ventricular function after myocardial infarction by inducing neovasculogenesis.

BACKGROUND: Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPCs) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that implantation of a tissue-engineered extracellular matrix (ECM) scaffold seeded with EPCs primed with SDF could induce borderzone neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after myocardial infarction. METHODS AND RESULTS: Lewis rats (n=82) underwent left anterior descending artery ligation to induce myocardial infarction. EPCs were isolated, characterized, and cultured on a vitronectin/collagen scaffold and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular wall, which included the region of ischemia. Control animals received sutures but no EPCM. Additional groups underwent application of the ECM alone, ECM primed with SDF (ECM+SDF), and ECM seeded with EPCs but not primed with SDF (ECM+SDF). At 4 weeks, borderzone myocardial tissue demonstrated increased levels of vascular endothelial growth factor in the EPCM group. When compared to controls, Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 versus 6.2 vessels/high-powered field; P<0.001), and microvascular perfusion measured by lectin microangiography was enhanced 4-fold (0.7% versus 2.7% vessel volume/section volume; P=0.04). Comparisons to additional groups also showed a significantly improved vasculogenic response in the EPCM group. Ventricular geometry and scar fraction assessed by digital planimetric analysis of sectioned hearts exhibited significantly preserved left ventricular internal diameter (9.7 mm versus 8.6 mm; P=0.005) and decreased infarct scar formation expressed as percent of total section area (16% versus 7%; P=0.002) when compared with all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure-volume conductance, and Doppler flow. CONCLUSIONS: Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after myocardial infarction.

Valve-sparing aortic root replacement and neochordal repair of complex aortic leaflet pathology for ruptured sinus of valsalva aneurysm fistulizing to the right ventricle.

Sinus of Valsalva aneurysms (SVAs) are rare congenital entities arising from eccentric aortic root dilatation that can protrude and rupture into adjacent cardiac chambers. Treatment entails aneurysmal sac excision and aortic defect closure. We present a young patient with a ruptured SVA fistulizing into the right ventricle and acute decompensated heart failure. He also had moderate aortic root enlargement and a dysmorphic aortic valve with 3 highly asymmetrical leaflets. This pathologic condition was successfully repaired with a novel combination of valve-sparing root replacement, aortic valve leaflet neochordal repair, right ventricular reconstruction, and tricuspid valve annuloplasty.

Ascending aortic cannulation in acute type a dissection repair.

Femoral and axillary cannulation for arterial inflow in acute type A aortic dissection are the most commonly used cannulation strategies in current practice. More recently, our group and others have successfully used a central cannulation technique with excellent results. Although this approach has been described, specific technical details have not been clearly defined. In addition, the ideal anatomic characteristics of different types of aortic dissections amenable to central cannulation have not been delineated. The purpose of this brief communication is to describe the technical and procedural details specific to cannulation of the dissected ascending aorta and to propose a classification scheme of ascending aortic dissection anatomy based on difficulty of central cannulation.

Transaortic mitral valve replacement.

Transaortic replacement of the mitral valve at the time of aortic valve or root replacement is a rarely used technique that offers many possible advantages in the setting of multivalve replacement. Reports in the literature are few and dated. The purpose of this brief communication is to describe technical and procedural details specific to mitral procedures done through the aortic annulus.

Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model.

OBJECTIVES: Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesized that stromal cell-derived factor 1α (SDF-1α) therapy to microrevascularize ischemic myocardium would rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity. METHODS: Immediately after left anterior descending coronary artery ligation, mice were randomly assigned to receive peri-infarct injection of either saline solution or SDF-1α. After 6 weeks, animals were killed and samples were taken from the peri-infarct border zone and the infarct scar, as well as from the left ventricle of noninfarcted control mice. Determination of tissues' elastic moduli was carried out by mechanical testing in an atomic force microscope. RESULTS: SDF-1α-treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline-treated peri-infarct myocardium (109 ± 22.9 kPa vs 295 ± 42.3 kPa; P < .0001). Myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF-1α-treated animals than in controls (804 ± 102.2 kPa vs 144 ± 27.5 kPa; P < .0001). CONCLUSIONS: Direct quantification of myocardial elastic properties demonstrates the ability of SDF-1α to re-engineer evolving myocardial infarct and peri-infarct tissues. By increasing elasticity of the ischemic and dysfunctional peri-infarct border zone and bolstering the weak, aneurysm-prone scar, SDF-1α therapy may confer a mechanical advantage to resist adverse remodeling after infarction.

Oxygen-dependent quenching of phosphorescence used to characterize improved myocardial oxygenation resulting from vasculogenic cytokine therapy.

This study evaluates a therapy for infarct modulation and acute myocardial rescue and utilizes a novel technique to measure local myocardial oxygenation in vivo. Bone marrow-derived endothelial progenitor cells (EPCs) were targeted to the heart with peri-infarct intramyocardial injection of the potent EPC chemokine stromal cell-derived factor 1α (SDF). Myocardial oxygen pressure was assessed using a noninvasive, real-time optical technique for measuring oxygen pressures within microvasculature based on the oxygen-dependent quenching of the phosphorescence of Oxyphor G3. Myocardial infarction was induced in male Wistar rats (n = 15) through left anterior descending coronary artery ligation. At the time of infarction, animals were randomized into two groups: saline control (n = 8) and treatment with SDF (n = 7). After 48 h, the animals underwent repeat thoracotomy and 20 µl of the phosphor Oxyphor G3 was injected into three areas (peri-infarct myocardium, myocardial scar, and remote left hindlimb muscle). Measurements of the oxygen distribution within the tissue were then made in vivo by applying the end of a light guide to the beating heart. Compared with controls, animals in the SDF group exhibited a significantly decreased percentage of hypoxic (defined as oxygen pressure ≤ 15.0 Torr) peri-infarct myocardium (9.7 ± 6.7% vs. 21.8 ± 11.9%, P = 0.017). The peak oxygen pressures in the peri-infarct region of the animals in the SDF group were significantly higher than the saline controls (39.5 ± 36.7 vs. 9.2 ± 8.6 Torr, P = 0.02). This strategy for targeting EPCs to vulnerable peri-infarct myocardium via the potent chemokine SDF-1α significantly decreased the degree of hypoxia in peri-infarct myocardium as measured in vivo by phosphorescence quenching. This effect could potentially mitigate the vicious cycle of myocyte death, myocardial fibrosis, progressive ventricular dilatation, and eventual heart failure seen after acute myocardial infarction.

Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction.

OBJECTIVES: Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. METHODS: EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n = 48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 µg/kg of SDF-1α, 3 µg/kg of spliced SDF analog, or 6 µg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. RESULTS: EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. CONCLUSIONS: A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α.

Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction.

OBJECTIVE: Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. METHODS: Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure-volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. RESULTS: Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure-volume measurements showed that cardiac function was preserved in these rats. CONCLUSIONS: Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.

OBJECTIVE: It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support. METHODS: We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support. RESULTS: Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10). CONCLUSION: When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.

Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support.

BACKGROUND: Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important. METHODS: We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007. RESULTS: Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need. CONCLUSIONS: The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.