Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

AIMS: Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS: Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION: Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION: This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

Two-dimensional speckle tracking strain analysis for efficacy assessment of myocardial cell therapy.

The subtle effects of transplanted bone marrow cells (BMC) on regional myocardial behavior in patients with ischemic heart disease are difficult to assess. Novel echocardiographic techniques can quantify regional myocardial deformation (strain) and distinguish between passive and active wall motion. We hypothesized that this technique may help delineate cell therapy-induced changes in regional LV contractility that escape clinical routine studies. Twelve patients with coronary artery disease and impaired LV function (LVEF &<35%) underwent CABG surgery plus intramyocardial injection of autologous bone marrow mononuclear cells. Between two and five predefined segments of ischemic myocardium per patient received BMCs, and untreated ischemic segments served as internal controls. Segmental echocardiographic analysis of peak systolic strain by speckle tracking was performed before and 1 year after surgery and compared with standard wall motion analysis. Two patients died during the follow-up period. In the remaining 10 patients, mean LVEF increased from 24.5 +/- 10% to 32.1 +/- 11% (p = 0.02). A moderate improvement of systolic function was noted in ischemic control segments by both wall motion score (WMS) and 2D strain echocardiography (2DSE). In BMC-treated segments, WMS improved slightly, but the data failed to reach statistical significance. As assessed by 2DSE, however, systolic function of BMC-treated segments improved by nearly 100%. 2DSE proved to detect BMC-induced change with 30-fold higher sensitivity than WMS, and the Receiver Operating Characteristic curve (ROC) confirmed the diagnostic precision of 2DSE (area-under-the-ROC = 0.87). We conclude that echocardiographic speckle tracking two-dimensional strain analysis can detect cell therapy-induced changes in regional contractile function that may escape detection by standard wall motion assessment. Thus, 2DSE may be a useful tool for the further development of clinical cardiac cell therapy.

Intramyocardial delivery of bone marrow mononuclear cells and mechanical assist device implantation in patients with end-stage cardiomyopathy.

In end-stage heart failure, mechanical ventricular assist devices (VAD) are being used as bridge-to-transplantation, as a bridge-to-recovery, or as the definitive therapy. We tested the hypothesis that myocardial implantation of autologous bone marrow mononuclear cells (BMNC) increases the likelihood of successful weaning from left VAD (LVAD) support. Ten patients (aged 14-60 years) with deteriorating heart function underwent LVAD implantation and concomitant implantation of autologous BMNC. Bone marrow was harvested prior to VAD implantation and BMNC were prepared by density centrifugation. Two patients received a pulsatile, extracorporeal LVAD and eight a nonpulsatile implantable device. Between 52 and 164 x 10(7) BMNC containing between 1 and 12 x 10(6) CD34+ cells were injected into the LV myocardium. There was one early and one late death. The median time on LVAD support was 243 days (range 24-498 days). Repeated echocardiographic examinations under increased hemodynamic load revealed a significant improvement of LV function in one patient. Three patients underwent heart transplantation, and four patients remain on LVAD support >1 year without evidence of recovery. Only one patient was successfully weaned from LVAD support after 4 months, and LV function has remained stable ever since. In patients with endstage cardiomyopathy, intramyocardial injection of BMNC at the time of LVAD implantation does not seem to increase the likelihood of successful weaning from VAD support. Other cell-based strategies should be pursued to harness the potential of cell therapy in LVAD patients.

Postnatal myocardial augmentation with skeletal myoblast-based fetal tissue engineering.

BACKGROUND: Cardiac anomalies constitute the most common birth defects, many of which involve variable myocardial deficiencies. Therapeutic options for structural myocardial repair remain limited in the neonatal population. This study was aimed at determining whether engineered fetal muscle constructs undergo milieu-dependent transdifferentiation after cardiac implantation, thus becoming a potential means to increase/support myocardial mass after birth. METHODS: Myoblasts were isolated from skeletal muscle specimens harvested from fetal lambs, labeled by transduction with a retrovirus-expressing green fluorescent protein, expanded in vitro, and then seeded onto collagen hydrogels. After birth, animals underwent autologous implantation of the engineered constructs (n = 8) onto the myocardium as an onlay patch. Between 4 and 30 weeks postoperatively, implants were harvested for multiple analyses. RESULTS: Fetal and postnatal survival rates were 89% and 100%, respectively. Labeled cells were identified within the implants at all time points by immunohistochemical staining for green fluorescent protein. At 24 and 30 weeks postimplantation, donor cells double-stained for green fluorescent protein and Troponin I, while losing skeletal (type II) myosin expression. CONCLUSIONS: Fetal skeletal myoblasts engraft in native myocardium up to 30 weeks after postnatal, autologous implantation as components of engineered onlay patches. These cells also display evidence of time-dependent transdifferentiation toward a cardiomyocyte-like lineage. Further analysis of fetal skeletal myoblast-based constructs for the repair of congenital myocardial defects is warranted.

Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation.

OBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND: Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS: We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS: We gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS: Percutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty.

Dynamic rotational seeding and cell culture system for vascular tube formation.

Optimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotational seeding and culturing of ovine vascular myofibroblasts onto biodegradable polymer scaffolds suitable for replacement of small- and large-diameter blood vessels. Large tubes (12 mm internal diameter and 60 mm length, n = 4) and small tubes (5 mm internal diameter and 20 mm length, n = 4) were made from a combination of polyglycolic acid/poly-4-hydroxybutyrate and coated with collagen solution. Tubes were then placed in culture vessels containing a vascular myofibroblast suspension (10(6) cells/cm(2)) and rotated at 5 rpm in a hybridization oven at 37 degrees C. Light and scanning electron microscopy analyses were performed after 5, 7, and 10 days. Myofibroblasts had formed confluent layers over the outer and inner surfaces of both large and small tubular scaffolds by day 5. Cells had aligned in the direction of flow by day 7. Multiple spindle-shaped cells were observed infiltrating the polymer mesh. Cell density increased between day 5 and day 10. All conduits maintained their tubular shape throughout the experiment. We conclude that dynamic rotational seeding and culturing in a hybridization oven is an easy, effective, and reliable method to deliver and culture vascular myofibroblasts onto tubular polymer scaffolds.

Clinical significance of PlA polymorphism of platelet GP IIb/IIIa receptors during long-term VAD support.

BACKGROUND: Although bleeding and thromboembolism remain major complications after implantation of ventricular assist devices (VADs), no standard anticoagulation protocols are available. Genetic polymorphism of platelet glycoprotein IIb/IIIa may contribute to the development of complications. The present study demonstrates a relationship between the PlA genotype and postoperative complications in patients implanted with pulsatile and axial flow VADs. METHODS: The PlA genotype was determined in 41 consecutive patients treated with a VAD who received anticoagulation with phenprocoumon and aspirin. Pulsatile Novacor (Novacor Corp, Oakland, CA) and Berlin Heart VADs (Berlin Heart, Berlin, Germany) were implanted in 28 patients and the axial flow MicroMed DeBakey VAD (MicroMed Technology, Inc, Houston, TX) in 13. The relationship between the PlA genotype, the anticoagulation regime, and bleeding and thromboembolic events was analyzed. RESULTS: There were no differences between patients with the A1A1 and A1A2 genotype regarding demographic characteristics, weight, or infection episodes. The international normalized ratio (INR), platelet activation tests, and doses of aspirin and dipyridamol before events were similar in both groups. Patients with the A1A1 genotype developed more bleeding complications (39% vs 0%, p = 0.021), while patients with the A1A2 genotype showed a tendency toward more thromboembolic events (13% vs 30%, p = 0.33). With regard to different types of VAD, patients with the axial flow DeBakey VAD and the A1A1 genotype developed significantly more bleeding complications (70% vs 0%, p = 0.033). CONCLUSIONS: In patients with a long-term VAD determination of PlA polymorphism and subsequent adjustment of the anticoagulation regime may lead to a reduction of bleeding and thromboembolic complications.

Influence of sex on ventricular remodeling after myocardial infarction in mice.

Murine models are increasingly used to elucidate the molecular mechanisms contributing to left ventricular (LV) remodeling. Epidemiologic and animal studies have suggested that women undergo differing patterns of LV remodeling than men after myocardial infarction (MI). We, therefore, sought to compare LV remodeling after MI in male and female mice. Echocardiography was performed in male and female C57BL6 mice before and serially after MI. Two days after MI, end-diastolic LV internal diameter and shortening fraction were similar in males and females. Between days 2 and 28 after MI, LV internal diameter increased in male mice but remained unchanged in female mice. During this time period, shortening fraction declined in males, but not in females. Posterior wall thickness increased more in females than in males. The size of the MI and the LV mass/body weight were similar between the 2 sexes after MI. Echocardiography showed that after MI, female mice undergo less extensive LV remodeling than males, with less dilation and better preserved LV systolic function 28 days after MI. These sex differences should be taken into account when studying murine cardiac adaptation to MI.

Development of a database of patients supported by ventricular assist devices.

An increase in the number of patients with end stage heart failure is leading to increased use of ventricular assist devices (VAD). However, sometimes the optimal time point for implantation of left ventricular or biventricular support remains unclear. Data analysis using an electronic database may help to make the decision making process more precise and thus improve outcome. However, it is not easy to find a balance between sufficient comprehensiveness of the data, which are selected from a huge amount of available information, and practicability of database maintenance and data analysis. We developed the Assist Database based on Access for Windows. The Assist Database consists of five main parts: (1) demographic and admission data, diagnosis, goal, and type of VAD; (2) preoperative period; (3) postoperative period up to 30 days; (4) follow-up period; and (5) statistical evaluation. The preoperative and postoperative parts include hemodynamic data; ventilatory support; laboratory results; results from echocardiographic, neurologic, pathologic, and other examinations; medication; and complications. The follow-up part documents readmissions, complications, and outcome. From April 1987 to October 2002, eight different types of VAD were implanted in 654 patients in our institution. Their data were retrospectively added to the Assist Database using medical records and different previously used electronic databases. Since the Assist Database came into routine use, it has been supplied daily with selected data of current patients. On the data entry level, the data arising from medical records are entered either manually via standard forms or automatically from other electronic documentation systems used in our hospital in routine patient care to collect laboratory results, demographic data, blood transfusion data, and operative data and from electronic patient charts via interfaces. The structure of the database is designed to facilitate the data analysis level. The database presented is one of three databases united to form a network. The structure of the Assist Database facilitates comprehensive, time saving data collection, which allows different online data analyses. These analyses may affect the decision making process and thus improve outcome. However, achieving a balance between the volume of available information, the time consumed, and the relevance of the data for further analysis remains difficult. The Assist Database should include information relevant for the decision making process and for the prediction of outcome. In particular, data collection should be focused on patients' preoperative condition and on postoperative organ function and quality of life. Further, different databases (for patients with congestive heart failure, assist device patients, and transplanted patients) should be unified to form a network to avoid the repeated collection of identical data, to save time, and to increase the quality of analysis. In the long-term, multicenter use of the Assist Database could be considered.

Advances in the mechanisms of cell delivery to cardiovascular scaffolds: comparison of two rotating cell culture systems.

Having a reliable method of delivering cells to polymer scaffolds in vitro is fundamental to the development of tissue engineered structures. This paper compares the efficacy of two rotating systems for this purpose. Ten conduits, measuring 40 mm by 10 mm, were fabricated from polyglycolic acid mesh and poly-4-hydrobutyrate. Five conduits were placed in a rotating wall vessel (RWV, Synthecon Inc., Houston, TX), developed by the National Aeronautics and Space Administration (NASA); five conduits were also placed in rotating individual sealed tubes (RISTs). Medium in the RWV was left unchanged for the duration of the experiment; medium in the RISTs required daily change. Samples of the discarded medium and samples from the RWV were analyzed for pH, pCO2, pO2, and lactate concentration. Constructs were assayed for DNA content as a surrogate for cell number. In the RWV, pH, pCO2, and pO2 remained stable, while the lactate concentration gradually increased. The measure of PO2 did not differ significantly between the RWV and the RISTs, but the pH was lower and the pCO2 and the lactate concentration measurements were higher in the RIST system at each time point (p = 0.001). After 6 days (p = 0.001), the total DNA per conduit was 226+/-7 microg for the conduits seeded in the RISTs and 396+/-18 microg for the conduits in the RWV, suggesting that the RWV is superior to the RIST system for delivering cells to polymer scaffolds.

Tissue engineering in the 21st century.

Traumatic and end-stage organ loss or tissue damage remains a devastating issue for everyone, and a major problem for millions of patients. It has been estimated that each year in the United States more than 8 million surgical operations are performed to solve these health problems.

Repair of anomalous origin of the left coronary artery from the pulmonary artery in infants and children.

OBJECTIVE: Although mortality after direct aortic reimplantation for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has significantly decreased, many questions remain unanswered. METHODS: Between 1986 and June 2010, we operated on 27 consecutive pediatric patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). All patients underwent reestablishment of a dual coronary system with direct aortic reimplantation of the left coronary artery into the aorta. Postoperative extracorporeal mechanical circulatory support was necessary in 7 cases. In all 7 patients, hemodynamic stability was achieved after 4 to 10 days of support. Mitral valve repair was performed in 9 patients with severe mitral valve incompetence and resulted in stable mitral valve function during follow-up as long as 19 years. RESULTS: There were no early or late deaths. During follow-up (3 months-17.5 years), both early and late improvement of myocardial function was observed in all patients. Reduced left ventricular regional function late after successful surgical correction of ALCAPA was related to the presence of left ventricular myocardial scar tissue, as detected by magnetic resonance imaging. CONCLUSIONS: Despite the absence of early and late mortality, the long-term prognosis for patients after reimplantation of ALCAPA into the aorta is not clear. Scars and perfusion deficits of the left ventricle may not be detected by standard echocardiographic evaluation of global left ventricular function and therefore may be underestimated. We therefore recommend lifelong surveillance of these patients, including magnetic resonance imaging.

Combined anterior mitral valve leaflet retention plasty and septal myectomy in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: Septal myectomy is the treatment of choice for patients with hypertrophic obstructive cardiomyopathy (HOCM) with significant left-ventricular outflow tract (LVOT) obstruction. In some HOCM patients, however, systolic anterior motion (SAM) of the anterior mitral leaflet significantly contributes to LVOT obstruction, resulting in mitral regurgitation and insufficient release of the obstruction after myectomy. We, therefore, developed a strategy of combined myectomy and anterior leaflet retention plasty (ALRP), and investigated its results in adult HOCM patients with manifest SAM. METHODS: Subaortic septal myectomy and ALRP were performed in 25 adult HOCM patients with significant SAM, as assessed by echocardiography (mean age = 48.5 ± 15 years). All patients received cardiac catheterization and echocardiography evaluation prior to the operation, before discharge, and at follow-up. Follow-up ranged between 0.8 and 14 years (median = 2.5 years). RESULTS: All patients survived the operation, and the Kaplan-Meier estimated survival was 100% at 1 year and 82 ± 6% at 5 years. Freedom from re-operation at 5 years was 83 ± 8%. The mean LVOT pressure gradient decreased from 84 ± 32 to 19 ± 11 mm Hg postoperatively (p < 0.001), and only two patients had mild residual or recurrent SAM at follow-up. Mitral regurgitation and New York Heart Association classification were also markedly improved at follow-up. CONCLUSIONS: Combined subaortic septal myectomy and ALRP is a safe and effective therapy in HOCM patients with significant SAM. ALRP can help prevent residual or recurrent LVOT obstruction and improves mitral regurgitation.

Predictors for the use of left ventricular assist devices in infants with anomalous left coronary artery from the pulmonary artery.

BACKGROUND: Left ventricular (LV) mechanical circulatory support (MCS) may be necessary after repair of anomalous left coronary artery from the pulmonary artery. We evaluated LV function parameters for their ability to predict postoperative need for MCS. METHODS: Fourteen infants (median age, 3.6; range, 2.3 to 12 months) underwent direct aortic reimplantation of the left coronary artery. We compared preoperative LV end-diastolic diameter, end-diastolic pressure, ejection fraction, and fraction of shortening of 8 patients with successful weaning from cardiopulmonary bypass (group 1) and 6 patients with unsuccessful weaning from cardiopulmonary bypass and temporary MCS support (group 2). RESULTS: No perioperative or late deaths occurred. All patients at follow-up were free of reoperation (median follow-up, 10.4 years [range, 1.4 to 17 years]). Median preoperative LV end-diastolic diameter (47 [range, 41 to 60 mm] vs 32 mm [range, 21 to 36 mm]) and LV end-diastolic pressure (20 [range, 18 to 25 mm Hg] vs 12 mm Hg [range, 7 to 20 mm Hg]) were significantly higher in group 2 than in group 1 (p = 0.002 and p = 0.048). LV ejection fraction (0.28 [range, 0.19 to 0.37] vs 0.43 [range, 0.23 to 0.76]) and LV fraction of shortening (9% [range, 7% to 15%] vs 22% [range 13% to 30%]) were significantly lower in group 2 than in group 1 (p = 0.035 and p = 0.002). MCS support duration ranged from 4 to 12 days. There were no significant differences in LV function parameters at discharge or during follow-up between the groups. CONCLUSIONS: A preoperative LV end-diastolic diameter above 40 mm is the strongest predictor for postoperative temporary MCS after anomalous left coronary artery from the pulmonary artery repair in infancy. However, even with temporary MCS, direct aortic reimplantation for anomalous left coronary artery from the pulmonary artery can be performed with no mortality and excellent LV recovery.

Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion.

This study compared the effects of rosuvastatin on left ventricular infarct size in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24 h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide synthase (NOS) expression, and mobilize progenitor stem cells after ischemic injury. Mice received blinded and randomized administration of rosuvastatin (20 mg.kg(-1).day(-1)) or saline from 2 days before surgery until death. After 60 min of ischemia with reperfusion, infarct size was reduced by 18% (P = 0.03) in mice randomized to receive rosuvastatin (n = 18) vs. saline (n = 22) but was similar after permanent occlusion in rosuvastatin (n = 17) and saline (n = 20) groups (P = not significant). Myocardial infarct size after permanent left anterior descending coronary artery occlusion (n = 6) tended to be greater in NOS3-deficient mice than in the wild-type saline group (33 +/- 4 vs. 23 +/- 2%, P = 0.08). Infarct size in NOS3-deficient mice was not modified by treatment with rosuvastatin (34 +/- 5%, n = 6, P = not significant vs. NOS3-deficient saline group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar in rosuvastatin and saline groups as was the percentage of CD34(+), Sca-1(+), and c-Kit(+) cells. Left ventricular NOS3 mRNA and protein levels were unchanged by rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia-reperfusion but not after permanent coronary occlusion, suggesting a potential anti-inflammatory effect. Although we were unable to demonstrate that the myocardial protection was due to an effect on neutrophil infiltration, stem cell mobilization, or induction of NOS3, these data suggest that rosuvastatin may be particularly beneficial in myocardial protection after ischemia-reperfusion injury.

Impact of body mass index on outcome in patients after coronary artery bypass grafting with and without valve surgery.

BACKGROUND: Among other preoperative parameters, extremely low or extremely high body mass index (BMI) has been discussed as a substantial risk factor for postoperative complications after cardiac surgery. However, the exact relationship between BMI and postoperative risk has not yet been defined. METHODS: We retrospectively investigated consecutive patients (n=22666) who underwent coronary artery bypass grafting with or without concomitant valve surgery between 1990 and 2001 in our institution. A number of preoperative and intraoperative variables and BMI (as a quadratic term) were used in a logistic regression model as covariates. Further, the patients were divided into 20 groups each with an increase in BMI of 1kg/m(2)(BMI as a categorical variable). The calculations of odds ratios (ORs) for re-intubation, infection, re-exploration, prolonged stay (>1 day) on the intensive care unit (ICU) and 30-day mortality were adjusted for age, gender and type of surgery. RESULTS: In the multivariate analysis only age (OR between 1.01 and 1.038, P<0.01), additional aortic valve (OR between 1.335 and 2.977, P<0.01) or mitral valve surgery (OR between 2.123 and 3.301, P<0.01) showed significant impact on all five end-points. Patients with BMI between 25 and 35kg/m(2)were not at elevated risk for any of the investigated end-points, except for infection. Patients with BMI between 21 and 27kg/m(2)were not at elevated risk for infection. The ORs for postoperative complications were significantly higher in underweight patients compared with obese or severely obese patients, except those for infection. Further, the underweight patients presented significantly more comorbidity. CONCLUSION: Patients with low BMI are at higher risk after cardiac surgery than obese or severely obese patients. We hypothesize that a preoperative focus on avoiding and/or reversing cachexia may be more efficacious than reducing obesity in reducing the overall risk associated with heart surgery.