A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF).

BACKGROUND: Autologous bone marrow mononuclear cell (ABMMNC) therapy has shown promise in patients with heart failure (HF). Cell function analysis may be important in interpreting trial results. METHODS: In this prospective study, we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF. Efficacy was assessed by maximal myocardial oxygen consumption, single photon emission computed tomography, 2-dimensional echocardiography, and quality-of-life assessment (Minnesota Living with Heart Failure and Short Form 36). We also characterized patients' bone marrow cells by flow cytometry, colony-forming unit, and proliferative assays. RESULTS: Cell-treated (n = 20) and control patients (n = 10) were similar at baseline. The procedure was safe; adverse events were similar in both groups. Canadian Cardiovascular Society angina score improved significantly (P = .001) in cell-treated patients, but function was not affected. Quality-of-life scores improved significantly at 6 months (P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36) over baseline in cell-treated but not control patients. Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients. The proportion of fixed defects significantly increased in control (P = .02) but not in treated patients (P = .16). Function of patients' bone marrow mononuclear cells was severely impaired. Stratifying cell results by age showed that younger patients (≤60 years) had significantly more mesenchymal progenitor cells (colony-forming unit fibroblasts) than patients >60 years (20.16 ± 14.6 vs 10.92 ± 7.8, P = .04). Furthermore, cell-treated younger patients had significantly improved maximal myocardial oxygen consumption (15 ± 5.8, 18.6 ± 2.7, and 17 ± 3.7 mL/kg per minute at baseline, 3 months, and 6 months, respectively) compared with similarly aged control patients (14.3 ± 2.5, 13.7 ± 3.7, and 14.6 ± 4.7 mL/kg per minute, P = .04). CONCLUSIONS: ABMMNC therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF.

Jugular venous oxygenation during hypothermic cardiopulmonary bypass in patients at risk for abnormal cerebral autoregulation: influence of alpha-Stat versus pH-stat blood gas management.

In a prospective, randomized study of cardiac surgical patients at risk for impaired cerebral blood flow autoregulation, we compared alpha-stat and pH-stat blood gas management. The 40 patients enrolled had age >70 yr, diabetes, prior stroke, or uncontrolled hypertension. During hypothermia and early rewarming, jugular oxygen tensions were significantly lower in alpha-stat patients (n = 12) than pH-stat patients (n = 19; P < 0.05). During rewarming, jugular venous desaturation (i.e., SjvO(2) <50%) occurred in 6 of 12 alpha-stat patients, but no pH-stat patients (P = 0.0006). Patients at risk for poor cerebral autoregulation have higher oxygen tensions and saturations if pH-stat blood gas management is used during cardiopulmonary bypass.

Comparative healing response after sirolimus- and paclitaxel-eluting stent implantation in a pig model of restenosis.

OBJECTIVE: We compared local vessel healing and inflammatory responses associated with nonoverlapping sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). BACKGROUND: Sirolimus and paclitaxel may have different effects on vascular healing. In the present study, we analyzed the local histologic effects of drug-eluting stents (DES). METHODS: We placed 43 stents (22 PES and 21 SES) in 16 Yucatan minipigs. Stents were randomly assigned and placed in the left anterior descending, circumflex, or right coronary arteries (one stent per artery), covering a region previously injured by balloon angioplasty. RESULTS: Histopathologic analysis showed that the distribution of injury scores was similar between the two stent groups, reflecting the homogeneity of coronary injury secondary to balloon overstretch. Electron microscopy showed complete endothelialization in most cases. Incomplete endothelialization was present in 12.5% of PES and almost 20% of SES at 30 days. In the PES group, moderate to severe inflammation was found in eight arteries, whereas only one vessel had moderate inflammation in the SES group. Severe inflammation was observed significantly more often in the PES than in the sirolimus group (P = 0.006). With the PES group, stent struts overlying side branches had a significantly higher frequency of poor endothelialization scores than did stent struts that did not overlay side branches (P = 0.006). CONCLUSIONS: In this preclinical study in a pig model of in-stent restenosis, implantation of nonoverlapping DES was associated with local inflammatory reactions and decreased endothelial repair. Impaired endothelialization was visualized in the struts overlying side branches.

Inflammatory protein levels and depression screening after coronary stenting predict major adverse coronary events.

BACKGROUND: Traditional risk factors cannot account for the majority of future major adverse coronary events (MACE) in patients diagnosed with heart disease. We examined levels of inflammatory proteins to be possible predictors of future MACE and physiological and psychological factors that initiate temporal increases in inflammatory protein levels. METHODS: Peripheral blood samples and depression data were collected 4 to 12 hr after elective coronary stent insertion in 490 patients. Depression screening was assessed by a single-question screening tool. Predictive modeling for future MACE was performed by using survival analysis, with time from the index event (placement of the stent) to future MACE as the dependent variable. RESULTS: Patients with high-sensitivity c-reactive protein (hsCRP) in the second and third quartiles were 3 and 2.5 times more likely to have a MACE than patients with hsCRP in the first quartile, respectively. As levels of vascular cell adhesion molecule and monocyte chemoattractant protein-1 increased, so did the risk of future MACE. Patients who screened positive for depression were approximately 2 times more likely to have a MACE within 24 months after stent placement than were patients who did not screen positive. CONCLUSIONS: Our results suggest that hsCRP, vascular cell adhesion molecule, and monocyte chemoattractant protein-1 levels, measured after coronary stent insertion in patients with coronary heart disease, are prognostic of future MACE. Furthermore, positive depression screening is an independent predictor of future MACE.

Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction.

This study assessed safety of transendocardial (TE) electromechanical-guided delivery of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (AMI) and compared intracoronary (IC) delivery with TE delivery. In a canine acute myocardial ischemia model, 100 x 10(6) MSCs were delivered 7 days after AMI via IC and TE routes. Functional assessment was performed by 2D echocardiogram, and detailed histopathologic analyses were performed to assess the impact of cell therapy in vascular density and fibrosis. Patterns of cell distribution in both delivery methods were also compared. There was a statistically significant reduction in the amount of myocardial ischemia in the TE group (P=0.007). Left ventricular ejection fraction (LVEF) increased 13% (mean) in the TE group (21-day follow-up) and was significantly better than that of the controls (P=0.01), but did not improve in the IC-delivery group. Dissimilar patterns of cell distribution were noted between the IC and TE groups. This study suggests that MSC treatment is probably safe and effective after AMI. In the comparison of TE and IC delivery, the TE group showed higher cell retention (clusters even in the injury center of the infarct) with an increased vascularity and greater functional improvement than did the IC group (no clusters; cells at the border of the infarct). The higher local cell density in the TE group may be important for therapeutic effectiveness.

Regional myocardial deformation in children with hypertrophic cardiomyopathy: morphological and clinical correlations.

AIMS: Hypertrophic cardiomyopathy (HCM) is a disease with marked regional differences in wall thickness. However, the relation between myocardial function and wall thickness has not been well studied. Ultrasonic strain rate (SR) imaging makes it possible to study the regional myocardial deformation. We investigated whether regional systolic deformation is reduced in paediatric patients with HCM and evaluated its relation with wall thickness, electrocardiographic pattern, and exercise capacity. METHODS AND RESULTS: We studied 41 children with asymmetric HCM (mean age 12.3 years) and 29 controls. Electrocardiograms, exercise testing (when feasible), and echocardiograms with tissue Doppler imaging were performed. Peak systolic SR, strain, post-systolic shortening, and time to maximal strain were calculated in the longitudinal direction from the basal septum, mid-septum, and basal lateral myocardial segments and in the radial direction from the basal antero-septal and infero-lateral myocardial segments. Children with HCM had a significant reduction in deformation in all myocardial segments when compared with controls. In the HCM group, peak systolic SR and strain were significantly lower in the basal septum when compared with the mid-septal and basal lateral myocardial segments. In the basal septum, post-systolic shortening was significantly higher and time to maximal strain significantly longer than in mid-septal and lateral myocardial segments. A strong inverse curvilinear relation between peak systolic strain and wall thickness was found (r = -0.86, P < 0.001), with no further decrease in the regional myocardial function demonstrated once maximal wall thickness exceeded a Z-score of 3.5. Peak systolic strain in the basal part of the septum correlated inversely with exercise capacity (r = 0.68, P < 0.01). CONCLUSION: Systolic deformation is significantly and inhomogeneously reduced in children with HCM. This reduction in myocardial function is related to maximal wall thickness and decreased exercise capacity.

The MBL2 'LYQA secretor' haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery.

BACKGROUND: Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705). CONCLUSIONS: The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery.

Delayed spinal cord deficits after thoracoabdominal aortic aneurysm repair.

BACKGROUND: Limited information is available about the treatment and outcomes of delayed paraplegia after thoracoabdominal aortic aneurysm (TAAA) repair. The objective of this study was to assess factors that precipitate and favorably affect delayed-onset neurologic deficits. METHODS: Over a 19-year period, 2,368 TAAA repairs were performed. Of the 93 patients (3.9%) who had postoperative paraplegia or paraparesis, 34 (37%) initially had intact neurologic function, but a delayed spinal cord deficit developed. We retrospectively examined clinical factors and events associated with development of the deficits, treatments used, and outcomes. Factors related to functional status were evaluated by comparing survivors who were ambulatory at discharge or transfer with those who were not. RESULTS: The delayed deficits occurred between 13 hours and 91 days postoperatively and were associated with a period of hypotension in 9 patients (26%). Two patients (6%) died in hospital. Of the 32 patients discharged or transferred, 13 (41%) were ambulatory. Poor functional outcomes were associated with female sex, intraoperative cerebrospinal fluid drainage, fewer intercostal arteries reattached, and administration of corticosteroids or osmotic diuretics. The actuarial survival rate at 2 years was 80% +/- 13% for the ambulatory patients and 32% +/- 12% for the nonambulatory patients (p = 0.002). CONCLUSIONS: Although precipitating episodes of hypoperfusion were common, most cases of delayed paraplegia occurred without such events, suggesting that other factors may play an important role in the development of this complication. Ambulatory status at discharge significantly predicts midterm survival.

Temperature during cardiopulmonary bypass: the discrepancies between monitored sites.

We performed studies in patients to determine whether temperature recordings from sites commonly monitored during hypothermic cardiopulmonary bypass adequately reflect cerebral temperature. In Study I (n = 12), temperatures monitored in the jugular bulb (JB) were compared with those recorded in the nasopharynx, esophagus, bladder, and rectum. In Study II (n = 30), temperature was also monitored in the arterial outlet of the membrane oxygenator. A calibrated recorder continuously and simultaneously recorded all temperatures. Study I found large temperature discrepancies between the JB and all other body sites during cooling and rewarming. There was considerable interindividual variability in the degree of discrepancy between the JB and other sites. Study II produced similar results but also showed that JB temperature reached equilibration with the temperature of blood entering the patient via the arterial outlet of the membrane oxygenator after cooling for 3.3 +/- 1.3 min and after rewarming for 16.5 +/- 5.5 min. Analysis of variance revealed that this arterial outlet site had the smallest average discrepancy of all temperature sites relative to the JB site (P < 0.001). In summary, temperatures measured in body sites over-estimated JB temperature during cooling and under-estimated it during rewarming, whereas arterial outlet blood temperature provided a good approximation.

Spectrum of aortic operations in 300 patients with confirmed or suspected Marfan syndrome.

BACKGROUND: Cardiovascular disease is the main cause of morbidity and mortality in patients with Marfan syndrome. Many patients with presumed Marfan syndrome do not meet current diagnostic criteria. This study reviews the surgical aspects of aortic disease in 300 patients referred with the diagnosis of Marfan syndrome. METHODS: During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs. Based on medical record review, patients were classified as confirmed Marfan syndrome if documented features satisfied current diagnostic criteria; patients not meeting these criteria were classified as suspected Marfan syndrome. RESULTS: There were 17 operative deaths (4.3%) after the 398 operations. Survival after the initial referral operation was 96.2% +/- 1.5% at 1 year, 82.7% +/- 2.4% at 5 years, and 74.6% +/- 3.1% at 10 years. Presentations, operative details, and outcomes were remarkably similar in the 137 patients (45.7%) with confirmed Marfan syndrome and the 163 patients (54.3%) with suspected Marfan syndrome. Freedom from repair failure, however, was significantly better in patients with confirmed Marfan syndrome (90.3% +/- 2.3% at 10 years) than in those with suspected Marfan syndrome (82.0% +/- 3.1% at 10 years; p = 0.001). CONCLUSIONS: Operative treatment of the full spectrum of aortic disease in Marfan patients enables excellent long-term survival. Similarities in surgical aspects of aortic disease suggest that patients with features of Marfan syndrome who do not meet diagnostic criteria should be managed in the same manner as patients with confirmed Marfan syndrome.

Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity.

BACKGROUND: Despite the fact that obesity is a known risk factor for cardiovascular disease, many studies have failed to demonstrate that obesity is independently associated with an increased risk of cardiovascular morbidity and mortality in nondiabetic patients undergoing coronary artery bypass graft surgery. The authors investigated the influence of obesity on adverse postoperative outcomes in diabetic and nondiabetic patients after primary coronary artery bypass surgery. METHODS: A retrospective cohort study of patients undergoing primary coronary artery bypass surgery (n = 9,862) between January 1995 and December 2004 at the Texas Heart Institute was performed. Diabetic (n = 3,374) and nondiabetic patients (n = 6,488) were classified into five groups, according to their body mass index: normal weight (n = 2,148), overweight (n = 4,257), mild obesity (n = 2,298), moderate obesity (n = 785), or morbid obesity (n = 338). Multivariate, stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications to determine whether obesity was independently associated with an increased risk of adverse postoperative outcomes. RESULTS: Obesity in nondiabetic patients was not independently associated with an increased risk of adverse postoperative outcomes. In contrast, obesity in diabetic patients was independently associated with a significantly increased risk of postoperative respiratory failure (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.41-3.61; P < 0.001), ventricular tachycardia (OR, 2.27; 95% CI, 1.18-4.35; P < 0.02), atrial fibrillation (OR, 1.56; 95% CI, 1.03-2.38; P < 0.04), atrial flutter (OR, 2.38; 95% CI, 1.29-4.40; P < 0.01), renal insufficiency (OR, 1.66; 95% CI, 1.10-3.41; P < 0.03), and leg wound infection (OR, 5.34; 95% CI, 2.27-12.54; P < 0.001). Obesity in diabetic patients was not independently associated with an increased risk of mortality, stroke, myocardial infarction, sepsis, or sternal wound infection. CONCLUSION: Obesity in diabetic patients is an independent predictor of worsened postoperative outcomes after primary coronary artery bypass graft surgery.

Salvaging the failing Fontan: lateral tunnel versus extracardiac conduit.

BACKGROUND: Since Fontan revision has been demonstrated to provide hemodynamic and symptomatic improvement in select patients with failing Fontan circulations, we now believe it is important to determine if one type of revision (lateral tunnel [LT] or extracardiac conduit [ECC]) provides superior outcomes. METHODS: Thirty-five Fontan revisions were performed (Jun 1997 to Dec 2004): 19 ECC (54%) and 16 LT. Preoperative variables were similar: New York Heart Association (NYHA) IV (LT = 4 vs ECC = 2, p = not significant [NS]), preoperative arrhythmias (LT = 13 vs ECC = 16, p = NS) and systemic right ventricle (LT = 4 vs ECC = 2, p = NS). Twenty-eight patients (80%) underwent a modified maze procedure (LT = 12 vs ECC = 16, p = NS) and 29 (83%) had pacemaker placement (LT = 11 vs ECC = 18, p < 0.05). RESULTS: There were no hospital deaths and no arrhythmias at hospital discharge. There were no differences in mean duration of intubation (LT 0.6 vs ECC 0.9 days, p = NS), inotropic support (LT 1.5 vs ECC 2.1 days, p = NS), intensive care unit stay (LT 2.6 vs ECC 3.5 days, p = NS), hospital stay (LT 8.8 vs ECC 9.7 days, p = NS), or episodes of acute postoperative arrhythmias (LT = 2 vs ECC = 4, p = NS). On intermediate follow-up (29 +/- 22 months), the overall cohort had 94% survival, 97% of survivors in NYHA class I/II, 91% freedom from late arrhythmias requiring medication, and no patient required cardiac transplantation. Follow-up revealed no differences in NYHA I/II (LT = 14 vs ECC = 18, p = NS), mortality (LT = 2 vs ECC = 0, p = NS), or late arrhythmia (LT = 4 vs ECC = 4, p = NS). CONCLUSIONS: Both the LT and ECC revisions provide symptomatic benefit for a failing Fontan connection and have equivalent early and intermediate results including arrhythmia recurrence.

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.

Alterations in alpha adrenoreceptor density and localization after mechanical left ventricular unloading with the Jarvik flowmaker left ventricular assist device.

Cardiac alpha one adrenoreceptors (alpha(1)AR) are known to mediate positive inotropism in human ventricular myocardium. In the early stages of heart failure, ventricular contractility is maintained by adrenergic stimulation, rennin-angiotensin activation, and other neurohormonal and cytokine system responses. As the disease progresses, however, these compensatory mechanisms cease to provide benefit; ventricular dilation and fibrosis occur and cardiac function deteriorates. When ventricular contractility becomes severely depressed and is no longer responsive to inotropic support, insertion of a left ventricular assist device (LVAD) may allow the left ventricle to rest, remodel, and recover some contractile function. Our previous work has demonstrated that the myocardium has the capacity to repair itself during a period of unloading, after which some patients are able to resume a normal lifestyle and no longer need a cardiac transplant.

Perturbations in laboratory values after coronary artery bypass graft surgery with cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to describe the sequential changes in commonly obtained laboratory values after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: The authors examined laboratory data from 375 patients who underwent uncomplicated CABG with CPB in a multicenter clinical trial of a medication for postoperative pain. Data were obtained preoperatively, at the time of postoperative extubation, and at 4 subsequent intervals ending 14 days after extubation. Data obtained before study drug administration are reported for all patients; thereafter, only data from placebo patients without perioperative complications (n=123) are reported. RESULTS: Mean postoperative coagulation values remained within their reference ranges at the time of extubation. However, platelet counts increased to a peak value well above the reference range by the end of the study. Postoperative white blood cell counts rose above the reference range, mainly because of increased neutrophils. Serum chemistries were also altered; most patients showed a persistent postoperative hyperglycemia. Creatine kinase levels rose to nearly 4 times the upper limit of the reference range in the early postoperative period. Lactate dehydrogenase, serum aspartate aminotransferase, and alanine aminotransferase levels also increased above the reference range. Total protein and albumin values were below the reference range throughout the postoperative period. CONCLUSIONS: Laboratory values for hematology, blood coagulation, and serum chemistry change substantially after uncomplicated CABG with CPB. Recognition of these changes will facilitate the conduct of clinical research and may prevent inappropriate treatment based on abnormal laboratory findings that have no clinical significance.

Lung cancer after heart transplantation: a 17-year experience.

BACKGROUND: The effects of heart transplantation on lung cancer incidence in heart transplant recipients are unclear. METHODS: In an observational study, we retrospectively reviewed the charts of all patients undergoing heart transplantation at our institution from July 1982 to July 1999. Data on lung cancer incidence, risk factors, treatment, and outcome were collected. RESULTS: Five hundred seventy-two patients (mean age, 50 +/- 11 years; range, 18 to 73) were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20 pack-year history of smoking before transplantation. Lung cancer developed in 2 patients 1 year or less after transplantation and in 8 patients more than 1 year after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up). Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8 months (range, 2 to 37.5). Routine annual chest radiographs after transplantation enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2 to 10.8]; p = 0.0002). CONCLUSIONS: The incidence of lung cancer in our population of heart transplant recipients appears to be no higher than in nontransplant populations with similar risk factors (ie, smoking and age). Routine radiographic imaging of transplant recipients may allow earlier detection of lung cancer and thus offer a survival benefit.

Factors predicting 10-year survival after heart transplantation.

BACKGROUND: We sought to identify factors predictive of long-term (>10-year) survival in heart transplant (HTx) recipients. METHODS: Four hundred fifteen adult patients underwent HTx at our institution between August 1982 and May 1997. The 158 patients who survived >10 years (Group A) and the 116 patients who died between 2 and 6 years (Group B) of HTx were compared in terms of gender, gender mismatch, ethnicity, age, height, weight, United Network for Organ Sharing status, type of induction therapy (OKT3 or anti-thymocyte globulin), infections (bacterial, viral, fungal and protozoal), cytomegalovirus (CMV) status, CMV mismatch, diabetes mellitus, hypertension and incidence of rejection episodes and transplant coronary artery disease within 2 years of HTx. RESULTS: Group A (135 men, 23 women; mean age 48 +/- 11 years) had significantly fewer post-HTx rejection episodes and viral, bacterial, fungal and total infections than did Group B (95 men, 21 women; mean age 49 +/- 12 years). Group A also had a significantly lower mean donor age, a lower incidence of pre-HTx diabetes, and a lower mean cholesterol level 1 year after HTx. In a multivariate analysis, fewer bacterial infections and rejection episodes after HTx, the absence of pre-HTx diabetes, and lower donor age were associated with longer survival. CONCLUSIONS: Pre-HTx diabetes, donor age and incidences of infection and rejection within 2 years of HTx predict long-term (>10-year) survival. Better control of infection and rejection during the first 2 years after HTx may improve survival.

Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model.

BACKGROUND: Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking. METHODS AND RESULTS: Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes. CONCLUSIONS: In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.

Catheter-based transendocardial delivery of autologous bone-marrow-derived mononuclear cells in patients listed for heart transplantation.

Growing evidence suggests that transplantation of autologous bone-marrow mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of ischemic myocardium. This procedure could potentially benefit transplant candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC injection, we performed a prospective, nonrandomized, open-label study in 5 heart transplant candidates with severe ischemic heart failure. Each patient underwent baseline single-photon emission computed tomography, a ramp treadmill protocol, 2-dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged electrocardiography, which were repeated at 2 and 6 months. Transendocardial delivery of ABMMNCs was done with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc each. There were no deaths, significant arrhythmias, or other major complications. The ABMMNC injection reduced the amount of ischemic myocardium (not statistically significant). More important, exercise test results improved significantly. Myocardial volume oxygen consumption increased from 10.6 +/- 3 mL/kg/min (baseline) to 16.3 +/- 7 mL/kg/min (2 months) and 23 +/- 7 mL/kg/min (6 months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the patients were no longer eligible for cardiac transplantation. In addition, metabolic equivalents improved from 3.03 +/- 0.66 (baseline) to 4.65 +/- 1.99 (2 months) and 6.5 +/- 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections were performed safely and resulted in improved exercise capacity. This technique may hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.