Takushi Kohmoto

Totally Endoscopic Atrial Septal Defect Repair With Robotic Assistance

Background—Computer (robotic) enhancement had emerged as a facilitator of minimally invasive cardiac surgery, and has been used to perform portions of intracardiac procedures via thoracotomy incisions. This report describes the next step in this progression—the first U.S. application of robotic technology for totally endoscopic open heart surgery. Methods and Results—Seventeen patients underwent repair of a secundum-type atrial septal defect (n=12) or patent foramen ovale (n=5) by a totally endoscopic approach, utilizing the Da Vinci robotic system. Cardiopulmonary bypass (CPB) was achieved peripherally. Cardioplegia was administered via the distal port of the arterial cannula after endo-balloon inflation. Via three port incisions in the right chest, pericardiotomy, bicaval occlusion, atriotomy, atrial septopexy, and atrial closure were performed by a surgeon seated at a computer console. A fourth 15-mm port was utilized for suction and suture passage by a patient-side assistant. The mean age of the patients was 47 years (range, 22 to 68). Aortic crossclamp time was 32 minutes (median), and CPB time was 122 minutes. In 16 patients, transesophageal echocardiography after 30 days confirmed successful repair. In one patient, a recurrent shunt was identified and repaired on postoperative day 5. Median length of stay (LOS) in the intensive care unit was 20 hours, and median hospital length of stay was 4 days. Conclusions—Robotic technology can be utilized to perform open heart procedures safely and effectively via totally endoscopic approaches. This technique represents an option for patients seeking a reliable ASD repair but wishing to avoid sternotomy or thoracotomy.

Top-Down Quantitative Proteomics Identified Phosphorylation of Cardiac Troponin I as a Candidate Biomarker for Chronic Heart Failure

The rapid increase in the prevalence of chronic heart failure (CHF) worldwide underscores an urgent need to identify biomarkers for the early detection of CHF. Post-translational modifications (PTMs) are associated with many critical signaling events during disease progression and thus offer a plethora of candidate biomarkers. We have employed a top-down quantitative proteomics methodology for comprehensive assessment of PTMs in whole proteins extracted from normal and diseased tissues. We systematically analyzed 36 clinical human heart tissue samples and identified phosphorylation of cardiac troponin I (cTnI) as a candidate biomarker for CHF. The relative percentages of the total phosphorylated cTnI forms over the entire cTnI populations (%P(total)) were 56.4 ± 3.5%, 36.9 ± 1.6%, 6.1 ± 2.4%, and 1.0 ± 0.6% for postmortem hearts with normal cardiac function (n = 7), early stage of mild hypertrophy (n = 5), severe hypertrophy/dilation (n = 4), and end-stage CHF (n = 6), respectively. In fresh transplant samples, the %P(total) of cTnI from nonfailing donor (n = 4), and end-stage failing hearts (n = 10) were 49.5 ± 5.9% and 18.8 ± 2.9%, respectively. Top-down MS with electron capture dissociation unequivocally localized the altered phosphorylation sites to Ser22/23 and determined the order of phosphorylation/dephosphorylation. This study represents the first clinical application of top-down MS-based quantitative proteomics for biomarker discovery from tissues, highlighting the potential of PTMs as disease biomarkers.

Lung transplantation with donation after cardiac death donors: Long-term follow-up in a single center

OBJECTIVE We sought to examine long-term outcomes at the University of Wisconsin for all lung transplant recipients who received lungs from donation after cardiac death donors since the initiation of this program in 1993. METHODS Eighteen (4.2%) of the 424 lung transplantations performed in 406 patients between January 1993 and April 2009 used lungs from donation after cardiac death donors. Outcomes for this recipient cohort were compared with those for recipients who received organs from brain-dead donors. RESULTS Warm ischemic time (from withdrawal of support to reperfusion of organs) was 30 +/- 17 minutes (11-93 minutes). The patient survival rates in the donation after cardiac death group (DCD group) at 1, 3, and 5 years were 88.1% +/- 7.9%, 81.9% +/- 9.5%, and 81.9% +/- 9.5%, respectively. These survival rates were not different from those of the brain-dead donor group (BDD group, P = .66). The incidence of primary graft dysfunction in the DCD group was similar to that of the BDD group (P = .59). However, the incidence of airway complications was somewhat higher in the DCD group. Freedom from bronchiolitis obliterans syndrome at 1, 3, and 5 years in the DCD group was 80.4% +/- 10.2%, 80.4% +/- 10.2%, and 72.3% +/- 11.9%, respectively, and did not differ from the incidence of bronchiolitis obliterans syndrome in the BDD group (P = .59). CONCLUSIONS Our data show that the long-term patient and graft survival rates after donation after cardiac death lung transplantation were equivalent to those after brain-dead donor lung transplantation. Our findings suggest that the use of donation after cardiac death donors can safely and substantially expand the donor pool for lung transplantation.

Hospital Readmissions After Continuous-Flow Left Ventricular Assist Device Implantation: Incidence, Causes, and Cost Analysis

BACKGROUND We investigated the incidence and causes of unplanned hospital readmissions after continuous-flow (CF) left ventricular assist device (LVAD) implantation. We also analyzed the impact of unplanned readmissions on post-CF-LVAD survival and the costs associated with each cause of readmission. METHODS We retrospectively reviewed 126 patients who underwent implantation with a CF-LVAD from January 2007 to December 2013. The timing of readmissions, hospital length of stay, and total length of device support were evaluated. Patients were followed up while receiving support, until transplantation, or until death. Direct hospital costs associated with each readmission were analyzed. RESULTS In all, 103 patients underwent implantation for bridge to transplantation and 19 patients for destination therapy; 68 patients were readmitted 156 times (2.2 times/patient) as of the end of follow-up. The median follow-up period was 11 months. While receiving device support, patients spent 93% of their time out of the hospital. The causes of readmission included gastrointestinal bleeding (19%), driveline infection (13%), and stroke (8%). The median time to first readmission was 35 days. Thirty (44%) patients were readmitted within 30 days after discharge. The median direct hospital cost of a single readmission was

Successful Radiofrequency Ablation Therapy for Intractable Ventricular Tachycardia With a Ventricular Assist Device

7,546. Device malfunction and arrhythmias were the most costly causes of readmission. There was no significant difference in long-term survival between readmitted patients and those who were not readmitted. CONCLUSIONS Gastrointestinal bleeding and CF-LVAD-related infections were the leading causes of readmission. Patients with a CF-LVAD spent 93% of their time out of hospital after implantation, and readmissions did not have a negative impact on long-term survival. New approaches to minimize these adverse events will continue to improve the efficacy and decrease the cost of CF-LVAD therapy.

Improved survival in patients with ventricular assist device therapy: the University of Wisconsin experience

Refractory ventricular tachycardia (VT) can be a potentially life-threatening rhythm in the presence of non-ischemic dilated cardiomyopathy, particularly when it results in hemodynamic compromise. A 65-year-old man with non-ischemic cardiomyopathy was referred for multiple episodes of VT. A HeartMate left ventricular assist device (LVAD) was implanted to stabilize and control the VT. However, he had multiple episodes of VT and the frequency of ventricular arrhythmias did not improve after LVAD implantation. He required electrical cardioversion to treat each episode. On Day 41 post-operatively, radiofrequency ablation was performed. Two significant areas of scarring were identified and were successfully ablated. After ablation, he did not have significant sustained VT episodes and was discharged.

Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro

OBJECTIVE Ventricular assist devices (VADs) have been implanted since 1990 in our institution, becoming an increasingly common treatment for end-stage heart failure. Beginning in 1997, VAD patients were discharged home when feasible. In August 2003, a dedicated multidisciplinary VAD team (cardiac surgeons, cardiologists, VAD coordinators, nurses, rehabilitation specialists, nutrition experts, psychologists, pharmacists, social workers, and administrators) was created to optimize the management of VAD patients. The purpose of this study is to analyze the impact of these changes in care at our center over the last 17 years. METHODS We retrospectively studied 107 consecutive VAD recipients between June 1990 and August 2006. VADs were implanted as bridge to recovery, bridge to transplant and destination therapy. The cohort was divided by care plans into early (n=37, June 1990-1996), mid (n=32, 1997-July 2003), and late groups (n=38, August 2003-August 2006). Demographic profile, survival and complications were assessed. RESULTS Patient demographics tended to show an increased severity of illness over time. Post-VAD survival rate significantly improved in the late group (post-VAD 1- and 3-year survival rates; early: 54.1% and 40.5%; mid: 51.6% and 41.9%; late: 86.8% and 82.5%, p<0.001, respectively). The incidence of complications including re-operation, major bleeding and major infection, significantly decreased in the late group (p<0.05). CONCLUSIONS Outcomes have improved dramatically in recent VAD patients, despite an increasingly high-risk patient population. These data suggest that advances in device technology and medical therapies, as well as a multidisciplinary approach, have improved survival on VAD therapy.

Improved Survival After Heart Transplantation in Patients With Bridge to Transplant in the Recent Era: A 17-year Single-center Experience

BACKGROUND AIMS For many years the human heart has been considered a terminally differentiated organ with no regenerative potential after injury. Recent studies, however, have cast doubt on this long-standing dogma. The objective of this study was to investigate the presence of and characterize mesenchymal stromal cells (MSC) in the adult mouse heart. The impact of MSC on growth and differentiation of adult cardiac stem cells (CSC) was also analyzed. METHODS A combination of lineage-negative/c-kit-negative (Lin(-)/c-kit(-)) immunoselection with a plastic-adhesion technique was used to isolate cardiac-derived MSC. The differentiation capacity and expression of surface markers were analyzed. To investigate the impact of MSC on growth and differentiation of adult CSC, Green Fluorescent Protein (GFP(+)) adult CSC were co-cultured with GFP(-) cardiac-derived MSC. RESULTS MSC were present in the adult mouse heart and they met the criteria established to define mouse MSC. They expressed surface markers and were able to differentiate, in a controlled manner, into multiple lineages. In addition, cardiac-derived MSC promoted the survival and expansion of adult CSC in vitro. CONCLUSIONS MSC can be isolated from the mouse heart and they promote growth and differentiation of adult CSC. The findings from this study could have a significant beneficial impact on future heart failure treatment. Co-culture and co-implantation of cardiac-derived MSC with adult CSC could provide extensive cardiac regeneration and maintenance of the CSC population after implanted into the heart.

Multidisciplinary approach decreases length of stay and reduces cost for ventricular assist device therapy

BACKGROUND Ventricular assist device (VAD) implantation as a bridge to transplant (BTT) has become an important approach for heart transplant candidates. In this study we document our institutional long-term results and recent improvements in BTT therapy. METHODS We retrospectively studied 531 consecutive heart transplant recipients between January 1990 and August 2007. The cohort was divided into old orthotopic heart transplant (OHT) without device (oOHT; n = 399, January 1990 to July 2003), old BTT (oBTT; n = 41, January 1990 to July 2003), new OHT without device (nOHT; n = 58, August 2003 to August 2007) and new BTT (nBTT; n = 33, August 2003 to August 2007) groups. Demographics and post-transplant outcomes were assessed. RESULTS Post-transplant survival in the nBTT group improved significantly compared with the oBTT group (log-rank test, p = 0.01) and survival in the nOHT group tended to be higher than in the oOHT group (p = 0.19). Survival in the oBTT group was significantly worse than in the oOHT group (p < 0.01). However, there was no difference between the nBTT and nOHT groups. The mean period of BTT support was 113 (range 5 to 524) days in the oBTT group and 148 (range 38 to 503) days in the nBTT group. Multivariate analysis revealed diabetes (p < 0.01) and biventricular support (p = 0.04) as significant independent predictors of post-transplant mortality. CONCLUSIONS Post-transplant survival has improved in recent BTT patients. Indeed, recent outcome for OHT after BTT has become equivalent to that for OHT without VAD. These data suggest that advances in device technology and our institutional multidisciplinary program have improved survival and allow BTT candidates to have an outcome equivalent to that of non-VAD patients in the recent era.

Effects of the HeartMate II left ventricular assist device as observed by serial echocardiography.

High implantation costs and long postoperative length of stay (LOS) in debilitated patients complicate ventricular assist device (VAD) therapy. Between July 2000 and February 2005, 30 patients received a VAD at our institution. Of those, 20 patients were successfully discharged from the hospital with VADs. In August 2003, a multidisciplinary team was formed consisting of all services for VAD patients to replace a single-discipline (cardiac surgery) system. This team evaluated potential VAD candidates and identified optimal timing for implantation. These 20 VAD patients were divided into two groups according to the initiation of multidisciplinary team; the traditional group (n=7, July 2000-July 2003) and the multidisciplinary group (n=13, August 2003-February 2005). Patient demographics were not different. The LOS decreased from 61 to 15 days (P<0.01), especially LOS on the floor decreased from 35 to 7 days (P=0.03). The floor cost was significantly reduced (