Search PubMed⌕ Search

Biomedical subjects

Yoshifumi Naka

Publications and source records attributed to Yoshifumi Naka.

At least 19 recordsLinked to original sources

Survival after heart transplantation is not diminished among recipients with uncomplicated diabetes mellitus: an analysis of the United Network of Organ Sharing database.

BACKGROUND: This study compares posttransplantation outcomes of survival and morbidity among recipients with and without diabetes mellitus (DM). METHODS AND RESULTS: The United Network of Organ Sharing (UNOS) provided deidentified patient-level data. Primary analysis focused on 20,412 first-time heart transplant recipients aged > or = 18 years who underwent transplantation between January 1, 1995, and December 31, 2005. To determine severity of DM, DM recipients were stratified by their aggregate number of diabetes-related complications (DRCs), including pretransplantation history of renal failure (serum creatinine = 2.5 mg/dL), peripheral vascular disease, cerebrovascular accident, and severe obesity (body mass index > or = 35 kg/m2). Kaplan-Meier analysis was performed to compare time to event. Although posttransplantation survival was significantly better (P<0.001) among patients without DM (median survival 10.1 years) than among those with DM (9.0 years), survival did not differ (P=0.08) between those without DM (10.1 years) and those with uncomplicated DM (0 DRCs; 9.3 years). Among those with DM, survival was worse with each additional DRC: 0 DRC, 9.3 years; 1 DRC, 6.7 years; and > or = 2 DRCs, 3.6 years. Although acute rejection and transplant coronary artery disease-free survival did not differ between groups, renal failure and severe infection-free survival were worse in those with DM and were inversely related to the number of DRCs. CONCLUSIONS: Posttransplantation survival among patients with uncomplicated DM was not significantly different than that among nondiabetics. However, when stratified by disease severity, recipients with more severe diabetes had significantly worse survival than nondiabetics. Therefore, although DM alone should not be a contraindication to heart transplantation, given the critical shortage of transplantable organs, maximal benefit may be achieved by exploring alternative treatment options in patients with severe DM. These include use of high-risk transplant lists and destination therapy.

Adult↗

The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections.

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.

Adhesins, Bacterial↗

Predictors and outcomes of continuous veno-venous hemodialysis use after implantation of a left ventricular assist device.

BACKGROUND: Post-operative renal failure is a common complication after left ventricular assist device (LVAD) implantation. This study was designed to evaluate predictors and outcomes of acute renal failure after LVAD insertion. METHODS: Two-hundred one patients undergoing LVAD implantation at a single institution from June 1996 through April 2004 were retrospectively analyzed. Patients were categorized into 2 groups: those who required post-operative continuous veno-venous hemodialysis (CVVHD) (Group 1, n = 65, 32.3%) and those who did not (Group 2, n = 136, 67.7%). Independent predictors of post-operative renal failure requiring CVVHD were determined using multivariate logistic regression techniques. RESULTS: Patients who had post-operative renal failure requiring CVVHD were older (53.7 +/- 12.9 vs 48.2 +/- 14.2 years, p = 0.009), had a higher incidence of intra-aortic balloon pump use (46.6% vs 26.2%, p = 0.006), and had a higher pre-operative mean LVAD score (5.8 +/- 3.5 vs 3.8 +/- 3.3, p = 0.001) than those without renal failure. LVAD score was the only independent predictor of post-operative renal failure requiring CVVHD (odds ratio = 1.226, p = 0.006). Sepsis rate was higher (33.3% vs 6.9%, p < 0.001) and bridge-to-transplantation rate was lower (52.4% vs 83.5%, p < 0.001) in Group 1 than in Group 2. Post-LVAD survival rates at 1, 3, 5 and 7 years for Group 1 and Group 2 were 43.2%, 39.1%, 34.7% and 34.7% vs 79.2%, 74.0%, 68.3% and 66.4%, respectively (log rank, p < 0.001). CONCLUSIONS: Acute renal failure necessitating CVVHD remains a serious complication after LVAD and confers significant morbidity and mortality. Pre-operative evaluation of patient risk factors and optimization of peri-operative hemodynamics are of utmost importance to prevent this major complication.

Acute Kidney Injury↗

The ligand/RAGE axis: lighting the fuse and igniting vascular stress.

Vascular inflammation contributes critically to the initiation and progression of atherosclerosis. These processes are accelerated in hyperglycemia and play key roles in the increased incidence and severity of myocardial infarction and stroke observed in diabetes. Evidence suggests that the ligands of the receptor for advanced glycation endproducts (RAGE), a multiligand member of the immunoglobulin superfamily, interact with this receptor to play important roles in both early development and progression of atherosclerosis and vascular inflammation. Studies in animal models of vascular injury underscored the potent impact of RAGE blockade; administration of ligand-binding decoys of RAGE or antibodies to the receptor reduced the consequences of diabetes, hyperlipidemia, and physical injury to the vessel wall. This review focuses on the ligand repertoire of RAGE, the impact of ligand-RAGE interaction, and the potent effect of RAGE blockade in rodent models of vascular injury.

Amyloid beta-Peptides↗

Clinical indication for use and outcomes after inhaled nitric oxide therapy.

BACKGROUND: Inhaled nitric oxide (iNO) use is widespread, but the long-term outcomes after therapy in adult patients remain unknown. METHODS: All 376 patients receiving perioperative iNO (excluding pediatric and interventional cardiology procedures) at Columbia University Medical Center were prospectively followed from 2000 to 2003. Survival data were collected from chart review. RESULTS: Inhaled nitric oxide was used to treat pulmonary and right ventricular failure in patients undergoing orthotopic heart transplantation (OHT, n = 67), orthotopic lung transplantation (n = 45), cardiac surgery (n = 105), and ventricular assist device placement (n = 66), and for hypoxemia in other surgery (n = 34) and medical patients (n = 59). Average follow-up was 2.9 +/- 1.0 years. Overall mortality was lowest when iNO was used after OHT (25.4%) and orthotopic lung transplantation (37.8%), intermediately after cardiac surgery (61%), ventricular assist device (62%), and other surgery patients (75%), and highest among medical patients (90%; all p < 0.005). The cost of iNO therapy was lower in transplantation versus medical patients, with a trend toward shorter duration of use. In multivariate analysis, respiratory failure and use in non-OHT were independent predictors of mortality (both p = 0.001). A risk score greater than 1 (score = non-OHT use 1, plus right ventricular failure 1) predicted a mortality of 76.5% versus 37.2% (p < 0.001). CONCLUSIONS: Use of iNO for pulmonary hypertension in patients undergoing OHT and orthotopic lung transplantation was associated with a significantly lower overall mortality rate compared with its use after cardiac surgery or for hypoxemia in medical patients. Inhaled nitric oxide does not appear to be cost effective when treating hypoxemia in medical patients with high-risk scores and irreversible disease.

Administration, Inhalation↗

Effect of clenbuterol on cardiac and skeletal muscle function during left ventricular assist device support.

BACKGROUND: High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown. METHODS: Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up-titrated to daily doses of 720 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation. RESULTS: There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p < 0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p < 0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p < 0.05). No significant change in myocyte size or collagen deposition was seen. CONCLUSIONS: Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery.

Adrenergic beta-Agonists↗

Off-pump epicardial atrial fibrillation surgery utilizing a novel bipolar radiofrequency system.

BACKGROUND: Over the past several years, pulmonary vein isolation for the treatment of atrial fibrillation has gained significant popularity. This study was undertaken to evaluate a novel radiofrequency (RF)-enabled clamp system designed to create transmural lesions epicardially on the beating heart using bipolar RF. METHODS: A set of differently shaped clamps modified to deliver bipolar RF energy were used to create a series of lesions in a beating heart canine model. The pulmonary veins and atrial appendages of 6 dogs were electrically isolated using bipolar RF energy. The right and left atrial appendages served as controls for the right and left pulmonary veins, respectively. Temperature-controlled RF energy was delivered to maintain a tissue temperature of 80 degrees C for 15 seconds. Electrical isolation was assessed acutely and after 4 weeks by a bipolar pacing protocol. RESULTS: A total of 24 circumferential lesions were created. By pacing analysis, 100% (24/24) of these lesions were electrically isolated acutely and 95% (19/20) were still isolated 4 weeks later. At 4 weeks, 92% (22/24) of lesions were transmural by histologic analysis, and 96% (23/24) demonstrated endocardial continuity. One animal experienced a fatal cardiac arrhythmia during initiation of the post-survival procedure, prior to electrophysiologic evaluation, accounting for the reduced number of potential electrically isolated lesions. CONCLUSION: Bipolar RF ablation utilizing a novel bipolar RF clamp device results in electrical isolation and histologic transmurality in an off-pump epicardial model.

Animals↗

Does a pre-left ventricular assist device screening score predict long-term transplantation success? A 2-center analysis.

BACKGROUND: A risk factor summation score was previously validated to successfully predict survival after insertion of a left ventricular assist device (LVAD). We investigated whether this scoring system also predicts clinical outcomes after eventual heart transplantation in LVAD recipients. METHODS: A retrospective review was performed on 153 consecutive patients who received an LVAD as a bridge to transplantation at 2 large-volume centers from 1996 to 2003. The scoring system was used to designate low- and high-scoring groups. RESULTS: Thirty-day mortality and 5-year survival after transplantation were equivalent between groups (4.46% versus 7.32% and 76% versus 70%, respectively). No difference was seen in length of posttransplantation ventilator dependence (2.83 +/- 0.49 versus 3.3 +/- 0.72 days) or intensive care unit monitoring (6.38 +/- 0.77 versus 6.97 +/- 1.1 days). However, low-scoring patients had a significantly decreased duration of inotrope support (5.57 +/- 0.45 versus 7.74 +/- 1.0 days, P = .035). CONCLUSION: A risk factor summation score may predict which LVAD patients will require prolonged inotropic support following heart transplantation. However, survival in high-risk (elevated score) LVAD patients following heart transplantation is comparable to low-risk groups, favoring the continued practice of LVAD implantation as a bridge to transplantation even in high-risk patients.

Female↗

Right heart failure after left ventricular assist device implantation in patients with chronic congestive heart failure.

BACKGROUND: Right heart failure (RHF) is not an infrequent complication of left ventricular assist device (LVAD) implantation. Few studies have examined outcomes for LVAD patients who subsequently develop RHF. This study details one center's experience with RHF in chronic congestive heart failure (CHF) patients. METHODS: One hundred eight patients with chronic CHF (>or=6 months) who underwent HeartMate LVAD implantation were identified during June 1996 to July 2004. Acute heart failure patients requiring LVADs were excluded to eliminate the impact of confounding non-cardiac factors. RHF was defined as the need for a subsequent right ventricular assist device (RVAD), >or=14 days of intravenous inotropes/pulmonary vasodilators, or both. Forty-two (38.9%) RHF patients were identified. Fourteen of these required RVAD insertion. Outcome parameters included early (<or=30-day) mortality, intensive care unit (ICU) length of stay (LOS), incidence of re-operation for bleeding and acute renal failure, and stroke, bridge-to-transplantation rate and post-transplantation survival rate. RESULTS: More female patients developed RHF than not (73.3% vs 26.7%, p = 0.003). RHF patients had a higher early mortality rate, greater ICU LOS, higher rates of re-operation for bleeding and renal failure, and lower bridge-to-transplantation rate than non-RHF patients (19.0% vs 6.2%, p = 0.039; 23.8 +/- 23.7 vs 9.6 +/- 7.1 days, p < 0.001; 38.9% vs 18.3%, p = 0.026; 61.0% vs 22.6%, p < 0.001; 65.0% vs 89.9%, p = 0.003; respectively). Fourteen (33.3%) RHF patients required RVAD insertion. Elevated intra-operative central venous pressure (CVP) was found to be an independent predictor of post-LVAD RHF. Overall bridge-to-transplantation rate for the entire study cohort was 73.1%. CONCLUSIONS: The development of RHF after LVAD insertion confers significant morbidity and mortality. Judicious application of inotropes and pulmonary vasodilators and timely RVAD insertion, if necessary, should be maintained. Further investigations evaluating pre- and intra-operative risk factors for the development of RHF are warranted.

Adult↗

Mechanical unloading leads to echocardiographic, electrocardiographic, neurohormonal, and histologic recovery.

BACKGROUND: Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery. METHODS: LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed. RESULTS: Thirty-six LVAD patients were prospectively followed for an average of 101 +/- 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% +/- 6.6% vs 33% +/- 8.1%, 7.1 +/- 1.2 cm vs 4.9 +/- 1.0 cm, respectively; both p < 0.001), with no improvement thereafter. At 30 days, QRS duration and QTc interval were significantly decreased from pre-LVAD (both p < 0.05). There was a marked reduction in BNP, myocyte size, and collagen deposition with LVAD support (all p < 0.01). In screening for markers of recovery, the decrease in QTc was inversely related to LVEDD at 60 days. Changes in QRS and myocyte diameter also correlated with the improvement in LVEF at 30 days. No patients had sufficient recovery for device explantation. CONCLUSIONS: We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.

Adolescent↗

Clinical outcomes in patients with chronic congestive heart failure who undergo left ventricular assist device implantation.

OBJECTIVE: The use of left ventricular assist devices as a bridge to transplantation for patients with chronic congestive heart failure is well accepted. However, few studies have examined outcomes solely for these patients. This study details one center's left ventricular assist device experience with this population. METHODS: Two hundred one patients received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif) from January 1, 1996, to April 30, 2004. Of these, 119 (59.2%) had chronic congestive heart failure (diagnosis >6 months) as the primary indication. Outcome parameters included early mortality after left ventricular assist device placement (<30 days), bridge-to-transplantation rate, and posttransplantation survival. Variables examined included patient demographic data; preoperative pacemaker, internal defibrillator, and balloon pump use; and preoperative laboratory values. RESULTS: Advanced age, female sex, and diabetes were independent predictors of early death (P = .048, odds ratio 1.879 per 10 years of age, 95% confidence interval 1.005-3.515; P = .002, odds ratio 10.029, 95% confidence interval 2.256-44.583; P = .040, odds ratio 3.974, 95% confidence interval 1.063-14.861). Advanced age, female sex, and low preoperative albumin were independent predictors of poor bridge-to-transplantation rate (P = .029, odds ratio 0.135 per 10 years of age, 95% confidence interval 0.022-0.819; P = .002, odds ratio 0.013, 95% confidence interval 0.001-0.197; P = .023, odds ratio 19.178 per 1 g/dL albumin, 95% confidence interval 1.504-244.598). There were no independent predictors of poor posttransplantation survival and prolonged intensive care unit stay. Overall bridge-to-transplantation rate was 81.5%. The 1-, 3-, 5-, and 7-year posttransplantation survivals were 88.4%, 84.5%, 78.4%, and 76.0%. CONCLUSION: Among patients with chronic congestive heart failure, advanced age, female sex, diabetes, and low preoperative albumin predict poor clinical course. Careful risk stratification and comprehensive evaluation by care providers should be performed for candidates who are female, are elderly, and have diabetes, and preoperative nutritional optimization should be encouraged to enhance patient outcomes.

Adult↗

Effect of diabetes on short- and long-term outcomes after left ventricular assist device implantation.

BACKGROUND: Diabetes mellitus (DM) is a frequent co-morbidity in patients with congestive heart failure (CHF). Implantation of LVADs is an acceptable option for diabetic patients with end-stage heart failure, yet no previous study has specifically examined the clinical outcomes of this patient population. METHODS: A retrospective analysis was performed on all patients who underwent LVAD insertion at a single institution from June 17, 1996 to April 14, 2004. Patients were divided into 2 groups: diabetics (DM) and non-diabetics (NDM). The groups were compared with regard to demographics, etiology of heart failure, body mass index (BMI), intensive care unit (ICU) stay, early mortality (< or =30 days), bridge-to-transplantation rate and post-LVAD and post-transplant survival. RESULTS: Two hundred one patients were identified. Of these, 49 (24.4%) had DM. Compared with the NDM group, DM patients had a higher mean body mass index (30.1 +/- 6.0 vs 26.1 +/- 4.8, p < 0.001) and a higher proportion of hypertension (57.4% vs 19.7%, p < 0.001). Although post-LVAD survival was similar, post-transplant survival in DM patients was significantly lower compared with NDM patients, with 1-, 3-, 5- and 7-year actuarial survival rates of 86.9%, 71.0%, 56.5% and 56.5% vs 90.5%, 88.4%, 83.0% and 80.7% (p = 0.020), respectively. CONCLUSIONS: Carefully selected diabetic patients can be successfully bridged to transplantation using LVADs with comparable outcomes to non-diabetic patients. Reasons for diminished post-transplant survival in this cohort are unclear and necessitate the conductance of multi-institutional studies to evaluate outcomes.

Adult↗

Coronary artery bypass grafting in patients with low ejection fraction.

BACKGROUND: Patients with low ejection fraction (EF) are at a higher risk for postoperative complications and mortality. Our objective was to assess the effect of low EF on clinical outcomes after coronary artery bypass grafting (CABG). METHODS AND RESULTS: We analyzed 55,515 patients from New York State database who underwent CABG between 1997 and 1999. Patients were stratified into 1 of the 4 EF groups: Group I (EF< or =20%), Group II (EF 21% to 30%), Group III (EF 31% to 40%), and Group IV (EF>40%). History of previous myocardial infarction, renal failure, and congestive heart failure were higher in patients with low EF (all P<0.001). Group I experienced a higher incidence of postoperative respiratory failure (10.1% versus 2.9%), renal failure (2.5% versus 0.6%), and sepsis (2.5% versus 0.6%) compared with Group IV. In-hospital mortality was significantly higher in Group I (6.5% versus 1.4%; P<0.001). Multivariate analysis showed hepatic failure [odds ratio (OR), 11.2], renal failure (OR, 4.1), previous myocardial infarction (OR, 3.4), reoperation (OR, 3.4), emergent procedures (OR, 3.2), female gender (OR, 1.7), congestive heart failure (OR, 1.6), and age (OR, 1.04) as independent predictors of in-hospital mortality in the low EF group. The discharges to home rate were significantly lower in Group I versus Group IV (73.1% and 87.7%, respectively; P<0.001). CONCLUSIONS: Patients with low EF are sicker at baseline and have >4 times higher mortality than patients with high EF. However, outcomes are improving over time and are superior to historical data. Therefore, CABG remains a viable option in selected patients with low EF.

Aged↗

A decade experience of cardiac retransplantation in adult recipients.

BACKGROUND: Cardiac retransplantation is considered to be the best therapeutic option for a failing cardiac allograft. However, poor outcomes with retransplantation have previously been reported, a factor that raises important ethical, logistic and financial issues given the limited organ donor supply. METHODS: Seven hundred sixty-six adult patients underwent cardiac transplantation for end-stage heart failure at our institution from 1992 to 2002. Of these, 41 (5.4%) were retransplants. Variables examined included recipient and donor demographics, indications for retransplant, comorbidities, cytomegalovirus (CMV) serology status, left ventricular assist device use before transplant, donor ischemic time, rate of early mortality (within 30 days), and post-transplantation survival rate. RESULTS: Indications for cardiac retransplant were transplant-related coronary artery disease in 37, acute rejection in 3, and other causes in 1. The mean interval between transplantation and retransplantation was 5.9 +/- 3.4 years. Baseline characteristics such as recipient age, gender, CMV serology status, and donor age were similar in the primary transplant and retransplant groups. Early mortality after transplantation was comparable between the 2 groups, but post-transplant survival was significantly lower in retransplant patients compared with primary transplants with 1-, 3-, 5-, and 7-year actuarial survival rates of 72.2%, 66.3%, 47.5%, and 40.7% vs. 85.1%, 79.2%, 72.9%, and 66.8%, respectively (p < 0.001). CONCLUSIONS: Cardiac retransplantation offers short-term outcomes similar to primary transplantation but lower long-term survival rates. Non-retransplant surgical options should also be considered in these patients. Careful patient selection and risk-assessment is necessary to govern appropriate allocation of limited donor organs.

Adult↗