Vivian M. Hsu

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.

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.

Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression

Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis.Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750±133500 vs. 901600±143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0±4.6 vs. 1.0±1.2 ng/ml, n=5, p=0.006) and western blot (1579400±477733 vs. 943000±157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.

Therapeutic Delivery of Cyclin A2 Induces Myocardial Regeneration and Enhances Cardiac Function in Ischemic Heart Failure

Background— Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2. Methods and Results— Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks. Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1±2.6 versus 9.3±1.1; P<0.0001), Ki-67 (46.3±7.2 versus 20.4±6.0; P<0.0001), BrdU (44.2±13.7 versus 5.2±5.2; P<0.05), and phosphohistone-H3 (12.7±1.4 versus 0±0; P<0.0001) positive cells/hpf. Cyclin A2 hearts demonstrated increased borderzone myofilament density (39.8±1.1 versus 31.8±1.0 cells/hpf; P=0.0011). Borderzone wall thickness was greater in cyclin A2 hearts (1.7±0.4 versus 1.4±0.04 mm; P<0.0001). Cyclin A2 animals manifested improved hemodynamics: Pmax (70.6±8.9 versus 60.4±11.8 mm Hg; P=0.017), max dP/dt (3000±588 versus 2500±643 mm Hg/sec; P<0.05), preload adjusted maximal power (5.75±4.40 versus 2.75±0.98 mWatts/&mgr;L2; P<0.05), and cardiac output (26.8±3.7 versus 22.7±2.6 mL/min; P=0.004). Conclusions— A therapeutic strategy of cyclin A2 expression via gene transfer induced cardiomyocyte cell cycle activation yielded increased borderzone myofilament density and improved myocardial function. This approach of inducing endogenous myocardial regeneration provides proof-of-concept evidence that cyclin A2 may ultimately serve as an efficient, alternative therapy for heart failure.

Fat Grafting’s Past, Present, and Future: Why Adipose Tissue Is Emerging as a Critical Link to the Advancement of Regenerative Medicine

Fat grafting is a common reconstructive and aesthetic procedure with extensive clinical applications. Recently, significant strides have been made in investigating the biology behind the success of this procedure. Surgeons and scientists alike have advanced this field by innovating fat graft harvesting and injection techniques, expanding the use of adipose tissue and its stem cell components, and broadening our understanding of the viability of fat grafting at the molecular and cellular levels. The objectives of this review are to (1) discuss the clinical applications of fat grafting, (2) describe the cellular biology of fat and the optimization of fat graft preparation, (3) illustrate the significance of adipose-derived stem cells and the potentiality of fat cells, (4) highlight the clinical uses of adipose-derived stem cells, and (5) explore the current and future frontiers of the study of fat grafting. Although collaborative knowledge has increased exponentially, many of the biological mechanisms behind fat grafting are still unknown. Plastic surgeons are in a unique position to pioneer both the scientific and clinical frontiers of fat grafting and to ultimately further this technology for the benefit of our patients.

Placental Growth Factor Provides a Novel Local Angiogenic Therapy for Ischemic Cardiomyopathy

Abstract  Background: Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy. Methods: Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence. Results: PlGF animals had increased angiogenesis compared to controls (22.8 ± 3.5 vs. 12.4 ± 3.2 endothelial cells/high‐powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 ± 0.2 vs. 9.2 ± 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 ± 0.1 vs. 1.38 ± 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 ± 4 vs. 73.7 ± 2 mmHg, p = 0.001), maximum dP/dt (4206 ± 362 vs. 2978 ± 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 ± 2 vs. 18.6 ± 1%, p = 0.02). Conclusions: Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

The modified V-Y dorsal metacarpal flap for repair of syndactyly without skin graft.

Background: Syndactyly repairs that use full-thickness skin grafts risk graft-related complications. The dorsal V-Y advancement flap offers a method of syndactyly release that can eliminate the need for full-thickness skin grafts in some cases of simple syndactyly. Methods: A retrospective case series of all patients undergoing syndactyly release without skin grafting performed by the senior author (B.C.) between 1998 and 2007 was conducted. All outpatient and inpatient charts were reviewed for pertinent patient demographics and clinical outcomes, including the incidence of web creep, hypertrophic scarring, flexion contracture, infection, angulation deformity, limited range of motion, ischemia, and need for reoperation. Results: A total of 28 syndactylies were included in the study: 25 simple incomplete and three simple complete. Mean follow-up time was 4.2 years. Mean operative time was 68 minutes. Two patients (7.1 percent) experienced postoperative complications; both were corrected by subsequent revision. Conclusion: The dorsal V-Y advancement flap without skin graft is an effective method of repair primarily in simple incomplete syndactyly.

Squamosal suture synostosis: a cause of atypical skull asymmetry.

Background: The squamosal suture is markedly different from the major calvarial sutures of the human skull. The unique properties of the suture are a result of the complex developmental biology of the temporal bone and biomechanical force exerted by surrounding structures. The dysmorphic effects of premature fusion of the suture, and possible treatment strategies in cases of synostosis, have received only brief description in the literature. Methods: A retrospective case series was performed. The study included patients evaluated by one of the senior authors (S.P.B., R.R.R., and D.J.S.) between 1993 and 2009. All pertinent patient data including inpatient and outpatient charts, photographic records, and radiographic scans were reviewed. Any management performed under the direction of a craniofacial surgeon was documented—including orthotic helmet therapy and operative management. Results: The study included 14 patients. Synostosis of the squamosal suture was noted to occur either in an isolated fashion or in the setting of other craniofacial malformations. Patients with isolated squamosal synostosis often suffered from a deformity that was mild in severity and tended to improve with time. However, when occurring in the setting of other forms of craniosynostosis, the deformity was often progressive, and transcranial surgery was frequently required. Conclusions: Synostosis of the squamosal suture can result in, or contribute to, significant craniofacial dysmorphism. The optimal form of therapy for this disorder is evolving.

Active thermoregulation improves outcome of off-pump coronary artery bypass.

During off-pump coronary artery bypass grafting, hypothermia increases vasoconstriction, myocardial afterload, coagulopathy and postoperative bleeding. Traditional thermoregulatory techniques do not maintain core body temperature intraoperatively. The efficacy of a commercially available, computer-controlled, water-circulating, dorsal surface, active warming system for thermoregulatory control was evaluated. All patients who underwent non-emergency off-pump coronary bypass grafting by a single surgeon in a 1-year period were studied: the thermoregulation device was used in 50 cases and unavailable for use in 19. The patients who underwent active thermoregulation demonstrated significantly improved core body temperatures compared to the controls: lowest intraoperative, 35.8°C ± 0.1°C vs. 35.0°C ± 0.2°C; immediately postoperative, 36.5°C ± 0.1°C vs. 35.6°C ± 0.2°C; and 1-hour postoperative, 36.6°C ± 0.1°C vs. 35.9°C ± 0.2°C. Thermoregulated patients had significantly reduced 24-hour chest tube drainage (764 ± 38 vs. 1227 ± 183 mL), packed red blood cell transfusions (1.4 ± 0.2 vs. 3.3 ± 0.7 units), time to extubation (6.8 ± 0.5 vs. 11.4 ± 2.3 hours), intensive care unit stay (1.3 ± 0.1 vs. 2.0 ± 0.3 days), and hospital stay (4.3 ± 0.1 vs. 5.1 ± 0.3 days).

Digital image correlation: a novel dynamic three-dimensional imaging technique for precise quantification of the dynamic rhytid and botulinum toxin type a efficacy.

Background: Quantification of facial dynamic motion is paramount for improving cosmetic and reconstructive surgical outcomes. The authors introduce digital image correlation using speckle tracking photogrammetry and Aramis software (GOM mbH, Braunschweig, Germany) to study facial dynamics and demonstrate its application in quantifying botulinum toxin efficacy. Methods: Fourteen subjects were evaluated using a dual camera system and three-dimensional optical analysis. Using Aramis software, the anatomic regions of the glabella, forehead, and total face were identified and highlighted. Tissue strain, defined as either compression or stretch, was measured within these regions over 36 frames during brow furrowing. Each patient was measured before and 2 weeks after injection of 20 units of onabotulinumtoxinA in the glabella. Average stretch and compression in treated areas were analyzed across all available frames. Results were compared using a Wilcoxon signed rank test. Results: After neurotoxin injection, average vertical stretch of the glabella during brow furrowing decreased from 2.51 percent to 1.15 percent (p < 0.05), and average vertical stretch in the forehead decreased from 6.73 percent to 1.67 percent (p < 0.05). Horizontal compression in the glabella decreased from 9.11 percent to 2.60 percent (p < 0.05) and from 4.83 percent to 0.83 percent (p < 0.05) in the forehead. Total facial major strain decreased from 4.41 percent to 3.05 percent (p < 0.05), and total facial minor strain decreased from 5.01 percent to 3.51 percent (p < 0.05). Conclusions: The authors introduce digital image correlation as a novel technology for measuring dynamic rhytid and neurotoxin efficacy. This technique allows for advancements in the study of dynamic aging and neuromuscular disorders. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.