[Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype]. / Le cophénotype sympathique efférent des fibres autonomes angiotensinergiques dans le cœur humain.

AIM: The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS: Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS: Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION: The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

Protective effect of focal adhesion kinase against skeletal muscle reperfusion injury after acute limb ischemia.

OBJECTIVES: In cardiac muscle, ischemia reperfusion (IR) injury is attenuated by mitochondrial function, which may be upregulated by focal adhesion kinase (FAK). The aim of this study was to determine whether increased FAK levels reduced rhabdomyolysis in skeletal muscle too. MATERIAL AND METHODS: In a translational in vivo experiment, rat lower limbs were subjected to 4 hours of ischemia followed by 24 or 72 hours of reperfusion. FAK expression was stimulated 7 days before (via somatic transfection with pCMV-driven FAK expression plasmid) and outcomes were measured against non-transfected and empty transfected controls. Slow oxidative (i.e., mitochondria-rich) and fast glycolytic (i.e., mitochondria-poor) type muscles were analyzed separately regarding rhabdomyolysis, apoptosis, and inflammation. Severity of IR injury was assessed using paired non-ischemic controls. RESULTS: After 24 hours of reperfusion, marked rhabdomyolysis was found in non-transfected and empty plasmid-transfected fast-type glycolytic muscle, tibialis anterior. Prior transfection enhanced FAK concentration significantly (p = 0.01). Concomitantly, levels of BAX, promoting mitochondrial transition pores, were reduced sixfold (p = 0.02) together with a blunted inflammation (p = 0.01) and reduced rhabdomyolysis (p = 0.003). Slow oxidative muscle, m. soleus, reacted differently: although apoptosis was detectable after IR, rhabdomyolysis did not appear before 72 hours of reperfusion; and FAK levels were not enhanced in ischemic muscle despite transfection (p = 0.66). CONCLUSIONS: IR-induced skeletal muscle rhabdomyolysis is a fiber type-specific phenomenon that appears to be modulated by mitochondria reserves. Stimulation of FAK may exploit these reserves constituting a potential therapeutic approach to reduce tissue loss following acute limb IR in fast-type muscle.

Covalent immobilisation of VEGF on plasma-coated electrospun scaffolds for tissue engineering applications.

Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 µm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations.

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization.

Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS).

Endovascular suitability and outcome after open surgery for ruptured abdominal aortic aneurysm.

BACKGROUND: Endovascular repair of ruptured abdominal aortic aneurysm (rAAA) has rapidly gained popularity, but superior results may be biased by patient selection. The aim was to investigate whether suitability for endovascular repair predicted survival, irrespective of technique of repair. METHODS: Two blinded investigators independently evaluated preoperative computed tomography angiograms of a consecutive cohort of patients with rAAA. Patients were categorized either 'suitable' or 'unsuitable' for endovascular repair, if assessments agreed. If assessments disagreed, they were classified 'borderline suitable'. Correlations between endovascular suitability and clinical outcome were adjusted for suspected confounding factors and tested for robustness using sensitivity analyses. RESULTS: A total of 248 patients with rAAA from January 2001 to December 2010 were included, of whom 237 (95·6 per cent) underwent open repair. Seventy patients (28·2 per cent) were classified as 'suitable' and 100 (40·3 per cent) as 'unsuitable' for endovascular repair; 63 (25·4 per cent) were considered 'borderline suitable'. Fifteen (6·0 per cent) could not be assessed and were included in the sensitivity analyses. The postoperative 30-day mortality rate was 15·3 per cent (38 deaths). Multiple logistic regression demonstrated that the odds of perioperative death increased 9·21 (95 per cent confidence interval 2·16 to 39·23) fold for 'unsuitable' rAAA (P = 0·003) and 6·80 (1·47 to 31·49) fold for 'borderline' rAAA (P = 0·014), compared with 'suitable' rAAA. This selection effect was robust across sensitivity analyses and sustained for at least 5 years of follow-up. CONCLUSION: Endovascular suitability was an independent and strongly positive predictor of survival after open repair of rAAA.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 µm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Acute pulmonary embolectomy three days following a coronary artery bypass graft procedure.

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.

Gene-mediated inhibition of the b-adrenergic receptor kinase: a new therapeutic strategy for heart failure.

Molecular changes that take place during the evolution of heart failure (HF), especially the well characterized beta-adrenergic receptor (betaAR) signaling abnormalities, represent attractive targets for myocardial gene therapy. The beta-adrenergic receptor kinase (betaARK1 or GRK2) is a cytosolic enzyme that phosphorylates only agonist-occupied betaARs as well as other G protein-coupled receptors (GPCRs), leading to desensitization and functional uncoupling. betaARK1 levels and activity are elevated in the failing heart and therefore, it has recently been evaluated as a potential target for novel HF treatment. This review summarizes recent results obtained in transgenic mouse models as well as in animals where a betaARK1 inhibitor peptide (betaARKct) was delivered via the coronary arteries by exogenous gene transfer. These results strongly suggest that betaARK1 inhibition may represent a significant improvement in HF therapy.

Vacuum assisted venous drainage does not increase trauma to blood cells.

Although gravity drainage has been the standard technique for cardiopulmonary bypass (CPB), the development of min imally invasive techniques for cardiac surgery has renewed interest in using vacuum assisted venous drainage (VAVD) Dideco (Mirandola, Italy) has modified the D903 Avant oxygenator to apply a vacuum to its venous reservoir. The impact of VAVD on blood damage with this device is analyzed. Six calves (mean body weight, 71.3 +/- 4.1 kg) were con nected to CPB by jugular venous and carotid arterial cannu lation, with a flow rate of 4-4.51 L/min for 6 h. They were assigned to gravity drainage (standard D903 Avant oxygen ator, n = 3) or VAVD (modified D903 Avant oxygenator, n = 3). The animals were allowed to survive for 7 days. A standard battery of blood samples was taken before bypass, throughout bypass, and 24 h, 48 h, and 7 days after bypass. Analysis of variance was used for repeated measurements. Thrombocyte and white blood cell counts, corrected by hematocrit and normalized by prebypass values, were not significantly different between groups throughout all study periods. The same holds true for hemolytic parameters (lactate dehydrogenase [LDH] and plasma hemoglobin). Both peaked at 24 hr in the standard and VAVD groups: LDH, 2,845 +/- 974 IU/L vs. 2,537 +/- 476 IU/L (p = 0.65), respectively; and plasma hemoglobin, 115 +/- 31 mg/L vs. 89 +/- 455 mg/L (p = 0.45), respectively. In this experimental setup with prolonged perfusion time, VAVD does not increase trauma to blood cells in comparison with standard gravity drainage.

Is an endocardial connection necessary for growth factor induced angiogenesis in transmyocardial laser revascularization?

Transmyocardial laser revascularization (TMLR) and therapeutic angiogenesis had emerged as potential tools in the treatment of angina refractory to conventional therapies. This combination might potentiate their effects, because angiogenesis is believed to be a basic mechanism in TMLR. The influence of channel connection with endocardial blood flow on angiogenesis is unclear. Twenty-five pigs (mean weight, 72.3 +/- 5 kg) were randomly assigned into five groups. In the transmural laser group, five transmyocardial channels were drilled. In the transmural mixed group, the same protocol was used followed by the injection of 100 microg of bovine bone derived growth factor mixture within each channel. The nontransmural laser group and the nontransmural mixed group underwent the same procedures, respectively, but the laser channels were drilled through the outer two-thirds of the myocardial wall. The control group had sham operations. Animals were allowed to survive for 1 month. Vascular densities were determined by computed morphometric analysis of histologic sections. Vascular counts of areas adjacent to the channels in the non- and transmural laser groups did not differ significantly from control groups (arteriolar counts: 0.27 +/- 0.16 and 0.26 +/- 0.16 vs. 0.29 +/- 0.11/mm2, respectively). When bovine bone protein growth factor mixture is added, neovascularization is increased significantly in non- and transmural mixed groups (1.04 +/- 0.79 and 0.69 +/- 0.37/mm2, respectively, p < 0.001 for both comparisons with corresponding laser groups), and there was no significant difference between mixed groups (p = 0.13). In this porcine model, the combination of TMLR with injection of bone protein growth factor mixture induced angiogenesis around the laser channels. Whether the channels did or did not communicate with the endocardial cavity did not influence the neovascular density.

Venous drainage with a single peripheral bicaval cannula for less invasive atrial septal defect repair.

New peripheral venous cannulae have recently been proposed for minimally invasive open cardiac surgery. We present a femoral venous cannula designed to simultaneously drain both superior and inferior vena cavae. Used in adult patients for atrial septal defect repair, the cannula allowed passive blood drainage of 70.6% +/- 11.7% of theoretical cardiac output. Drainage was augmented to 93.4% +/- 8.6% of theoretical cardiac output by means of a centrifugal pump.

Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a beta-adrenergic receptor kinase inhibitor.

BACKGROUND: Acute cardiac contractile dysfunction is common after cardiopulmonary bypass (CPB). A potential molecular mechanism is enhanced beta-adrenergic receptor kinase (betaARK1) activity, because beta-adrenergic receptor (betaAR) signaling is altered in cardiomyocytes after cardioplegia. Therefore, we examined whether adenovirus-mediated intracoronary delivery of a betaARK1 inhibitor (Adv-betaARKct) could prevent post-CPB dysfunction. METHODS AND RESULTS: Rabbits were randomized to receive 5x10(11) total viral particles of Adv-betaARKct or PBS. After 5 days, hearts were arrested with University of Wisconsin solution, excised, and stored at 4 degrees C for 15 minutes or 4 hours before reperfusion on a Langendorff apparatus. Left ventricular (LV) function measured by end-diastolic pressure response to preload augmentation, contractility (LV dP/dt(max)), and relaxation (LV dP/dt(min)) was assessed by use of increasing doses of isoproterenol and compared with a control group of nonarrested hearts acutely perfused on the Langendorff apparatus. In the PBS-treated hearts, LV function decreased in a temporal manner and was significantly impaired compared with control hearts after 4 hours of cardioplegic arrest. LV function in Adv-betaARKct-treated hearts, however, was significantly enhanced compared with PBS treatment and was similar to control nonarrested hearts even after 4 hours of cardioplegia. Biochemically, several aspects of betaAR signaling were dysfunctional in PBS-treated hearts, whereas they were normalized in betaARKct-overexpressing hearts. CONCLUSIONS: Myocardial gene transfer of Adv-betaARKct stabilizes betaAR signaling and prevents LV dysfunction induced by prolonged cardioplegic arrest. Thus, betaARK1 inhibition may represent a novel target in limiting depressed ventricular function after CPB.

Reshaping the remodelled left ventricle: a new concept.

OBJECTIVE: Based on the law of Laplace, transventricular tension members were designed to diminish wall stress by changing the left ventricle (LV) globular shape to a bilobular one, thus reducing the ventricular wall radius of curvature. This concept was tested in a model of congestive heart failure. METHODS: Seven calves were used for the study (74.3+/-4.2 kg). Treatment efficacy was assessed with sonomicrometric wall motion analysis coupled with intraventricular pressure measurement. Preload increase was applied stepwise with tension members in released and tightened position. RESULTS: Tightening of the tension members improved systolic function for CVP>10 mmHg (dP/dt: 828+/-122 vs. 895+/-112 mmHg/s, P=0.019, for baseline and 20% stress level reduction respectively; wall thickening: 11.6+/-1.5 vs. 13.3+/-1.7%, P<0.001) and diastolic function (LV end-diastolic pressure: 15.9+/-4.8 vs. 13.6+/-2.7 mmHg, P<0.001, for CVP>10 mmHg; peak rate of wall thinning: -12.2+/-2.2 vs. -14+/-2.3 cm(2)/s, P<0.001 and logistic time constant of isovolumic relaxation: 48.4 +/-10.9 vs. 39.8+/-9.6ms, P<0.001, for CVP>5 mmHg). CONCLUSIONS: This less aggressive LV reduction method significantly improves contractility and relaxation parameters in this model of congestive heart failure.

Are standard human coagulation tests suitable in pigs and calves during extracorporeal circulation?

The thrombogenicity of membrane oxygenators as well as clotting parameters profiles, using standard human clotting tests, was analyzed in calves and pigs during 6 h perfusion. Three calves and 3 pigs were connected to extracorporeal circulation with standard heparinization. Blood samples were taken for coagulation variables throughout perfusion, and oxygenators were examined for clot deposits at the end of the experiment. Two out of 3 oxygenators of the calf group presented clot deposits while none in the pig group did. Baseline coagulation variables of pigs showed values similar to those of humans while neither extrinsic nor intrinsic pathways could be activated in calves with standard human coagulation tests. The calf model, in conclusion, was confirmed to be a difficult model for the testing of extracorporeal circulation device resistance to thrombus formation, which is, however, not reflected by standard human coagulation tests. The pig model is a better model in which both coagulation pathways could be activated with standard human coagulation tests.

Tricuspid valve involvement in combined mitral and aortic valve surgery.

BACKGROUND: Combined mitral and aortic valve disease requiring surgery may involve the tricuspid valve as well. Our treatment policy is conservative especially for tricuspid regurgitation which is operated on when severe only. METHODS: A retrospective study was performed at a tertiary and secondary referral center for cardiovascular disease. Over a 15-year period, 65 consecutive patients underwent aortic and mitral surgery with concomitant tricuspid regurgitation and/or stenosis. Fifty-five/65 (85%) patients were in NYHA class III-IV. Fifty-eight/65 (89%) patients had tricuspid regurgitation secondary to right chamber dilatation and 7/65 (11%) had tricuspid stenosis and/or regurgitation because of previous endocarditis. Twenty-two/65 (34%) tricuspid valves were operated on: 18/22 (82%) de Vega annuloplasty, 2/22 (9%) commissurotomies and 2/22 (9%) prosthetic valves. Mortality and complications were recorded during a mean follow-up of 5.3 yrs (range, 6 months-15.3 yrs). Event-free survivals were determined using the Kaplan-Meier method. RESULTS: Hospital mortality was 6.2% (4/65) and the complication rate was 18.5% (12/65). The freedom from late valve related mortality and morbidity at 5, 10 and 15 years was 86+/-5.5%, 81.9+/-6.8%, and 81.9+/-6.8% respectively. One valve related complication was due to the tricuspid valve. At last follow-up, 87% (47/54) of the survivors were in NYHA class I-II. CONCLUSIONS: With a conservative policy of tricuspid valve intervention, functional results of this patient population are good and long-term valve related morbidity and mortality are mainly related to the mitral and aortic valve procedures.

Intrachannel versus interchannel application of angiogenic factors in transmyocardial laser revascularization.

BACKGROUND AND OBJECTIVE: Theoretically myocardial angiogenesis of laser injury can be further enhanced by the addition of angiogenic growth factors. The influence of the way of administration of these factors on vascular growth around the channels is still unclear. MATERIALS AND METHODS: 18 pigs (mean weight 72 +/- 5.2 kg) were randomized to either triads of transmyocardial laser revascularization (TMLR) channels (group 1, n = 6) or isolated channels (group 2, n = 6), or a control group (n = 6). The animals had injections of bovine bone derived growth factor mixture either in the center of the triads in group 1 or within the channels themselves in group 2. Animals were sacrificed one month later for histological analysis. RESULTS: The vascular densities of myocardial areas within the triads of group 1 and around the channels in group 2 were significantly larger than in the control group: 15.2 +/- 3.7/mm2 and 14.2 +/- 3.5/mm2 respectively vs 5.3 +/- 1.6/mm2 (p < 0.001 for both differences). Differences of densities between group 1 and 2 were not statistically significant (p = 0.6). CONCLUSIONS: In this porcine model, the addition of a bovine bone derived growth factor mixture to TMLR significantly stimulates angiogenesis in the areas adjacent to the channels. The place of injection does not influence the angiogenesis intensity.

Does laser injury induce a different neovascularisation pattern from mechanical or ischaemic injuries?

AIM: To analyse the arteriolar pattern of laser induced channels and their surroundings compared with mechanical and ischaemic injury. METHODS: 24 pigs were randomised to a myocardial infarction group, a transmyocardial laser revascularisation group, a needle group, or a control group. In the laser revascularisation and needle groups, five channels were created either with a 1.75 mm probe holmium-YAG laser or a Tru-cut needle of the same size. Animals were killed 28 days later. Morphometric analysis of vascular density was expressed as the mean (SD) number of arteriolar structures/cm(2). RESULTS: Laser and needle channels were completely invaded by granulation tissue. Their surface areas did not differ significantly: 2.28 (0.7) mm(2) and 2.38 (1.1) mm(2), respectively (p = 0.82). Within both types of channel, arteriolar density was significantly increased in comparison with the myocardial infarction scar: 197 (52)/cm(2) and 190 (64)/cm(2), respectively (p = 0.8) versus 56 (20)/cm(2) (p < 0.001 for both comparisons). The area of 1 mm width immediately adjacent to the laser and needle channels showed a density of 25 (16)/cm(2) and 23 (18)/cm(2), respectively, which is similar to that of normal tissue (28 (10)/cm(2); p = 0.6 and p = 0.4, respectively). The mean arteriolar diameter was similar throughout all the regions analysed. CONCLUSIONS: Both laser and needle channels produce a similar increase in arteriolar structures, which is limited to the lesion itself. This suggests that laser injury is not more potent as an angiogenic stimulator than mechanical injury, which in turn is superior to infarction.

Atrial, ventricular, or both cannulation sites to optimize left ventricular assistance?

The efficiency of left ventricular assist devices (LVADs) depends on the capacity of the inflow cannula to drain blood into the pump. Left atrial (LA) and left ventricular (LV) sites were compared in an animal model mimicking different hemodynamic conditions. Three calves (56.3+/-5.0 kg) were equipped with a Thoratec LVAD. A regular cardiopulmonary bypass (CPB) circuit was used as a right ventricular assist device (RVAD) (jugular vein/pulmonary artery), and preload conditions were adjusted by storage (or perfusion) of blood into (or from) the venous reservoir. LA and LV drainage, tested separately or simultaneously, was measured by its effect on the LVAD's performance. The LVAD was used alone on a beating heart or together with the RVAD (biVAD) on a beating and on a fibrillating heart. Increasing the central venous pressure (CVP) highlighted the differences between the LA and LV cannulation sites when the LVAD was tested either alone or together with the RVAD (biVAD) on a beating heart. Drainage through the LA or the LV was similar when CVP was set at 8 mm Hg, and increasing CVP to 14 mm Hg allowed for better drainage through the LV cannula. In contrast, after induction of fibrillation to mimic extreme heart failure, the drainage was better through the LA cannula. Using both LA and LV cannulae simultaneously did not improve the LVAD output in any of the conditions tested. LV cannulation provides better blood drainage when used on a normal beating heart and, therefore, allows for increased LVAD performance. However, in severe heart failure, blood drainage through the LV cannula decreases and the LA cannulation site is superior.