An in silico twin for epicardial augmentation of the failing heart.

Advances in ventricular assist device (VAD) technology for the treatment of end-stage congestive heart failure (CHF) are needed to cope with the increasing numbers of patients that cannot be provided with donor hearts for transplantation. We develop and investigate a novel extravascular VAD technology that provides biventricular, epicardial pressure support for the failing heart. This novel VAD concept avoids blood contact that is accompanied with typical complications such as coagulation and infections. To date, in vivo porcine model results with a prototype of the implant exist, further studies to improve the implant's performance and promote its applicability in humans are needed. In this contribution, we present a personalised functional digital twin of the heart, the vascular system, and the novel VAD technology in terms of a calibrated, customized computational model. The calibration procedure is based on patient-specific measurements and is performed by solving an inverse problem. This in silico model is able to (a) confirm in vivo experimental data, (b) predict healthy and pathologic ventricular function, and (c) assess the beneficial impact of the novel VAD concept to a high level of fidelity. The model shows very good agreement with in vivo data and reliably predicts increases in stroke volume and left ventricular pressure with increasing ventricular support. Furthermore, the digital twin allows insight into quantities that are poorly or not at all amenable in any experimental setup. Conclusively, the model's ability to link integral hemodynamic variables to local tissue mechanical deformation makes it a highly valuable tool for the dimensioning of novel VAD technologies and future treatment strategies in heart failure. The presented in silico twin enhances in vivo studies by facilitating the accessibility and increasing the range of quantities of interest. Because of its flexibility in the assessment of design variants and optimization loops, it may substantially contribute to a reduction of the amount of animal experiments in this and similar settings.

Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced Porcine Failing Heart Model.

For treatment of advanced heart failure, current strategies include cardiac transplantation or blood-contacting pump technology associated with complications, including stroke and bleeding. This study investigated an individualized biventricular epicardial augmentation technology in a drug-induced porcine failing heart model. A total of 11 pigs were used, for the assessment of hemodynamics and cardiac function under various conditions of support pressures and support durations (n = 4), to assess device positioning and function by in vivo computer tomographic imaging (n = 3) and to investigate a minimally invasive implantation on the beating heart (n = 4). Support pressures of 20-80 mm Hg gradually augmented cardiac function parameters in this animal model as indicated by increased left ventricular stroke volume, end-systolic pressures, and decreased end-diastolic pressures. Strong evidence was found regarding the necessity of mechanical synchronization of support end with the isovolumetric relaxation phase of the heart. In addition, the customized, self-expandable implant enabled a marker-guided minimally invasive implantation through a 4 cm skin incision using fluoroscopy. Correct positioning was confirmed in computer tomographic images. Continued long-term survival investigations will deliver preclinical evidence for further development of this concept.

A monolithic 3D-0D coupled closed-loop model of the heart and the vascular system: Experiment-based parameter estimation for patient-specific cardiac mechanics.

A model for patient-specific cardiac mechanics simulation is introduced, incorporating a 3-dimensional finite element model of the ventricular part of the heart, which is coupled to a reduced-order 0-dimensional closed-loop vascular system, heart valve, and atrial chamber model. The ventricles are modeled by a nonlinear orthotropic passive material law. The electrical activation is mimicked by a prescribed parameterized active stress acting along a generic muscle fiber orientation. Our activation function is constructed such that the start of ventricular contraction and relaxation as well as the active stress curve's slope are parameterized. The imaging-based patient-specific ventricular model is prestressed to low end-diastolic pressure to account for the imaged, stressed configuration. Visco-elastic Robin boundary conditions are applied to the heart base and the epicardium to account for the embedding surrounding. We treat the 3D solid-0D fluid interaction as a strongly coupled monolithic problem, which is consistently linearized with respect to 3D solid and 0D fluid model variables to allow for a Newton-type solution procedure. The resulting coupled linear system of equations is solved iteratively in every Newton step using 2  ×  2 physics-based block preconditioning. Furthermore, we present novel efficient strategies for calibrating active contractile and vascular resistance parameters to experimental left ventricular pressure and stroke volume data gained in porcine experiments. Two exemplary states of cardiovascular condition are considered, namely, after application of vasodilatory beta blockers (BETA) and after injection of vasoconstrictive phenylephrine (PHEN). The parameter calibration to the specific individual and cardiovascular state at hand is performed using a 2-stage nonlinear multilevel method that uses a low-fidelity heart model to compute a parameter correction for the high-fidelity model optimization problem. We discuss 2 different low-fidelity model choices with respect to their ability to augment the parameter optimization. Because the periodic state conditions on the model (active stress, vascular pressures, and fluxes) are a priori unknown and also dependent on the parameters to be calibrated (and vice versa), we perform parameter calibration and periodic state condition estimation simultaneously. After a couple of heart beats, the calibration algorithm converges to a settled, periodic state because of conservation of blood volume within the closed-loop circulatory system. The proposed model and multilevel calibration method are cost-efficient and allow for an efficient determination of a patient-specific in silico heart model that reproduces physiological observations very well. Such an individual and state accurate model is an important predictive tool in intervention planning, assist device engineering and other medical applications.

Hybrid debranching and TEVAR of the aortic arch off-pump, in re-do patients with complicated chronic type-A aortic dissections: a critical report.

BACKGROUND: Patients suffering from acute type A aortic dissection undergo replacement of the ascending aorta, the proximal hemiarch or complete aortic arch, depending on the extent of the individual pathology. In a subset of these treated patients, secondary pathologies of the distal anastomosis or the remaining distal part of the aorta occur. The treatment of these pathologies is challenging, requiring major surgical re-do procedures with aortic arch replacement under extracorporeal circulation and hypothermic circulatory arrest. METHODS: We report our experience of five patients with complex aortic pathologies after previous aortic surgery treated with a single stage re-do hybrid procedure, consisting of bypass grafting of the supraaortic branches off-pump, stent graft placement for endovascular aortic repair (TEVAR) and surgical debranching of the aortic arch. RESULTS: In all patients the surgical vascular grafts and stent grafts were deployed successfully, there were no intraoperative deaths. Four out of five patients were discharged from hospital in good clinical condition. One patient died postoperatively due to cardiac tamponade. In one patient a type I endoleak persisted leading to occlusion of a bypass branch requiring surgical revision at one year after debranching. CONCLUSION: We discuss the prerequisites, all steps and potential pitfalls of this hybrid aortic arch replacement. The current procedure avoids cardiopulmonary bypass and circulatory arrest, which may benefit early patient outcome; however, patient and device selection plays a key role for immediate success and midterm outcomes. In addition, precise procedural planning and development of customized stents may help to develop this procedure into a true alternative for conventional aortic arch replacement.

Fibrin sealant patch for repair of acute type a aortic dissection.

INTRODUCTION: The use of glues to repair disrupted tissue during acute type-A aortic dissection (TAD) surgery may be discontinuous, and cause embolization and cell necrosis. We report a method of fibrin sealant patch (FSP) to reinforce dissected aortic tissue with a collagen double layer coated with fibrinogen/thrombin on either side (TachoSil®; Takeda, Konstanz, Germany). METHODS: In 12 patients (seven male, 66.9 ± 11.7 years) with acute TAD we performed FSP of the intima-media disruption at the proximal and distal anastomosis of the aorta. We analyzed the perioperative course and echocardiographical, radiological, and clinical outcomes up to one year. Additionally, we investigated the adhesive potential of the FSP in vitro. RESULTS: In vitro, the adhesive strength of the FSP was 60 N/cm(2). In-hospital mortality was 8.3% (n = 1), recovery was satisfactory with no major neurologic events, mean ICU stay was 13.6 ± 6.0 days, mean hospital stay was 20.7 ± 4.4 days. A total of 7.0 ± 2.6 RBC, 3.4 ± 1.5 platelets, and 8.0 ± 4.3 FFP were transfused. One-year survival was 83.3%. In 6/6 DeBakey II dissections the intimal tear was completely resected, in 2/6 DeBakey I dissections the false lumen in the descending aorta completely collapsed. No redissections and no relevant aortic valve insufficiencies were seen during follow-up. CONCLUSION: This analysis shows that FSP using a collagen matrix double layer coated with fibrinogen/thrombin is feasible, safe, and effective in repairing the dissected aortic tissue. It results in continuous reinforcement of aortic tissue and completely avoids the need for conventional glues.

Asymptomatic melanoma of the superior cavo-atrial junction: The challenge of imaging.

METASTATIC LESIONS IN THE SUPERIOR VENA CAVA AND THE RIGHT ATRIUM ARE DIFFICULT TO DIAGNOSE: in computed tomography (CT), they are easily misinterpreted as artifacts, and the same region may be difficult to access using echocardiography. We present a case of asymptomatic metastasis of a malignant melanoma which was overlooked initially due to deficiencies in imaging. Using 18F-fluorodeoxyglucose positron emission tomography-CT, the metastasis was clearly identified and finally treated successfully. We discuss the diagnostic value of the various imaging modalities for intracardiac masses.

Patient-centered cardiopulmonary bypass concepts.

This review outlines and discusses the newest technologies used for cardiopulmonary bypass (CPB) including changes in pump technology, oxygenators, filters, and priming. In addition, evidence-based and experience-based procedures are presented in line with the recommendations given on what CPB-related practices are safe and effective.

A rat model of cardiopulmonary bypass with cardioplegic arrest and hemodynamic assessment by conductance catheter technique.

BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce systemic inflammation and cardiac dysfunction associated with a significant morbidity. Aim of the study was to develop an in vivo model of rat CPB with hypothermic cardiac arrest and the use of cardioplegia. MATERIAL AND METHODS: The CPB circuit consisted of a venous reservoir, membrane oxygenator, heat exchanger, and roller pump. CPB was instituted in adult male Wistar rats (400-500 g) for 60 min at a flow rate of 120 ml x kg(-1) x min(-1), including 15 min cooling to 32 degrees C, 30 min cardiac arrest with the use of cold crystalloid cardioplegia after aortic cross clamping, and 15 min of reperfusion and rewarming to 37 degrees C. Arterial blood pressure (MAP) and heart rate (HR) were monitored, arterial blood samples were analyzed. Left ventricular (LV) function parameters were assessed by intraventricular conductance catheter. Important technical aspects are: ventilation is required during partial bypass; anticoagulation should be performed immediately prior to CPB to reduce blood loss; active suction on venous drainage allows higher pump flows; and the small priming volume of the extracorporeal circuit (8 ml) avoids the need for donor blood. RESULTS: MAP remained stable prior to and during CPB.MAP and HR were significantly decreased 60 min after weaning from bypass. Hct was significantly lowered after hemodilution, but remained stable during CPB and 60 min after weaning from bypass. BE and pH remained stable throughout the experiment.Without inotropic support diastolic and systolic LV function parameters were impaired after 30 min of cardioplegic arrest followed by 15 min of reperfusion. Myocardial TNF-alpha mRNA levels were slightly increased (1.28-fold, p = 0.71), and IL-6 mRNA was significantly increased in the cardioplegia group (90.3-fold, p = 0.001). Both IL-6 and TNF-alpha plasma levels were significantly elevated in the cardioplegia group (TNF-alpha: 4.6-fold increase,p < 0.05; IL-6: 426.8-fold increase, p < 0.001). CONCLUSIONS: We have developed a rat CPB with mild hypothermic cardioplegic arrest. This rodent model is suitable to study clinically relevant problems related to CPB,myocardial protection and systemic inflammation.

Partial median "I" sternotomy: minimally invasive alternate approach for aortic valve replacement.

Minimally invasive aortic valve replacement using the inversed L-like partial upper sternotomy has evolved during the last 10 years. It is performed with excellent results with regard to sternal stability and cosmesis. However, the lateral incision may result in sternal overriding, instability, or fracture. We present an alternate minimally invasive approach to aortic valve replacement. We performed a partial median "I" sternotomy in 30 consecutive patients: After a 6- to 8-cm skin incision, the sternum was incised from the jugulum downward to the corpus, ending at the level of the fourth or fifth intercostal space. No lateral incision of the sternum was performed. The access to the heart and aorta was excellent. During the postoperative course and during follow-up, clinical examination revealed sternal stability and normal wound healing in all patients. These results show that the partial median I sternotomy can be performed safely and provides excellent clinical and cosmetic results.

Autonomic control in patients experiencing atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) occurs in 20-40% of patients after open heart surgery and leads to an increased morbidity and prolonged hospital stay. Earlier studies have demonstrated that depressed baroreflex function predicts mortality and major arrhythmic events in patients surviving myocardial infarction. Cardiac surgery per se leads to decreased baroreflex sensitivity (BRS) and heart rate variability (HRV). Hence, the present study was aimed at analyzing the impact of the cardiovascular autonomous system on the development of postsurgical AF. METHODS AND RESULTS: The study covered 51 patients who consecutively underwent aortic valve replacement, coronary artery bypass surgery, or combined procedures. Noninvasive blood pressure and ECG were recorded the day before and 24 hour after surgery. BRS, linear as well as nonlinear HRV parameters were calculated using established methods. Eighteen patients developed AF during the first postoperative week, while 33 remained in sinus rhythm (SR) throughout the observation period. Patients with postoperative (PostOp) AF exhibited a significantly reduced preoperative (PreOp) BRS in terms of bradycardic and tachycardic regulation (average delayed slope [ms/mmHg]: SR: PreOp: 9.83 +/- 3.26, PostOp: 6.02 +/- 2.29, Pre-Post: P < 0.001; AF: PreOp: 7.59 +/- 1.99, PostOp: 6.39 +/- 3.67, Pre-Post: P < 0.044; AF vs SR: PreOp: P < 0.01, PostOp: ns). In both groups, surgery caused a decrease of BRS and HRV. Analysis of nonlinear dynamics revealed a tendency toward decreased system complexity caused by the operation; this trend was significant in patients remaining in sinus rhythm. CONCLUSIONS: Patients experiencing postoperative AF obviously suffer from an impaired BRS before surgery already. These findings may be used to guide prophylactic antiarrhythmic therapy.

Severe superior vena cava syndrome after transvenous pacemaker implantation.

Superior vena cava syndrome is a rare complication after pacemaker implantation. The present report outlines how underestimation of clinically relevant symptoms of superior vena cava syndrome early after pacemaker implantation may result in severe complication with the need for major surgical intervention. Superior vena cava syndrome should be diagnosed early because immediate thrombolytic therapy is effective in the majority of patients and avoids the requirement for interventional or surgical efforts.

Graft function, histopathology and morphometry of radial arteries used as conduits for myocardial revascularization in patients beyond age 70.

BACKGROUND: Coronary artery bypass grafting (CABG) using radial arteries has become a standard procedure for younger patients in many centers. However, advanced atherosclerotic changes may limit its use in older patients. We studied the effects of age on morphologic and histopathologic findings in CABG patients aged 70 years and older. METHODS: In 31 consecutive patients aged 70-85 (mean 77+/-8 years) scheduled for elective CABG, the left or right radial artery (RA) was used to graft the second target vessel (first graft: LIMA-LAD). Preoperative Doppler flow and Allen's test were satisfactory. Intraoperatively the distal segment adjacent to the anastomosis site of the RA was collected for histologic evaluation. Intraoperative angiography, measurement of flow, and resistance index (PI) were performed to document graft quality. Histopathology and morphometry were used to measure intimal and medial areas (IA, MA; microm2), intimal thickening index (ITI), relation between intimal and medial width at maximum intimal thickness (IMR), and percentage of luminal narrowing (%LN). RESULTS: The RA showed no evidence for stenosis of the conduits or the anastomosis. In all grafts flow and PI were satisfactory (76+/-14 ml/min; PI: 2.2+/-0.9). Histopathology and morphometry showed atherosclerotic changes in all RA grafts: IA: 890+/-971 (range 286-5244), MA: 2751+/-818 (range 1357-4989), ITI: 0.26+/-0.09 (range 0.12-0.44), IMR: 0.59+/-0.28 (range 0.21-1.13) %LN: 38+/-5 (range 13.2-61.7). Age as well as classic risk factors including diabetes, hypertension, smoking, and hyperlipidemia did not correlate with RA atherosclerosis. CONCLUSIONS: Excellent macroscopic and angiographic results were obtained. All grafts used showed minor to moderate atherosclerotic changes without severely altered indices of intimal thickening or luminal narrowing. The radial artery must be used with caution; however, age should not be an exclusion criterion per se.

Persistently increased systemic, but not cardiac-specific, adhesion molecule expression and coronary endothelial dysfunction in human cardiac allografts.

BACKGROUND: Adhesion molecules are involved in inflammatory processes that alter endothelial function and lead to impairment of coronary vasomotor function. We studied a possible relationship between systemic expression, cardiac-specific expression, or both of P-selectin and intercellular adhesion molecule 1 and coronary vasomotor function both 1 and 12 months after heart transplantation in human subjects. METHODS: The expression of endomyocardial and soluble forms of P-selectin and intercellular adhesion molecule 1, as well as levels of tumor necrosis factor alpha, were determined in aortic and coronary sinus blood samples 1, 6, and 12 months after heart transplantation in 42 transplant recipients and 20 age-matched, nontransplanted control subjects. In addition, both endothelium-dependent (acetylcholine) and endothelium-independent (adenosine) coronary vasomotor function were assessed by using a Doppler flow wire and quantitative coronary angiography 1 and 12 months after heart transplantation. RESULTS: Adhesion molecules were highly expressed 1 month after heart transplantation and remained at high levels 12 months after heart transplantation when compared with levels in nontransplanted control subjects. No cardiac-specific expression or release of P-selectin or intercellular adhesion molecule 1 was observed. There was a significant inverse correlation between coronary vasomotor function and soluble adhesion molecule expression both 1 and 12 months after heart transplantation. CONCLUSION: Persistently high levels of circulating adhesion molecules are of systemic, but not cardiac-specific, origin and reflect a chronic inflammatory state throughout the first year after heart transplantation. This is associated with impairment of coronary vasomotor function, an early and potentially reversible step in the process of atherothrombosis and transplant coronary artery disease.

Rest and exercise performance of the Medtronic Advantage bileaflet valve in the aortic position.

BACKGROUND: The aim of the study was to evaluate rest and exercise performance and left ventricular mass regression of the Medtronic Advantage (Medtronic, Inc, Minneapolis, MN) prosthesis in the aortic position at 1 year at a single center as part of a multicenter, prospective clinical trial. METHODS: Between May 2002 and June 2003, 63 consecutive patients underwent aortic valve replacement with a Medtronic Advantage prosthesis (84.1% male; mean age, 56.0 +/- 9.7 years; ejection fraction, 56.5 +/- 15.8%). Valve lesions were stenosis (n = 20), mixed (n = 34), and insufficiency (n = 9). Concomitant procedures were performed in 34.9%. Follow-up was 100% complete. Echocardiographic data were obtained early postoperatively and at 1 year, combined with stress echocardiography by treadmill. Mean pressure gradients, stroke volume, and left ventricular mass were determined by echocardiography. Data are presented as mean +/- standard deviation. RESULTS: Operative mortality was 0%. Valve-related complications were observed in 2 patients (endocarditis, n = 1; thromboembolic event, n = 1). There was no case of antithromboembolic hemorrhage, prosthesis-related explant, or reoperation. One patient showed moderate paravalvular regurgitation. Mean pressure gradients 1 year postoperatively ranged from 6.3 to 11.0 mm Hg across all valve sizes. Left ventricular mass regression at 1 year was 18.4% across all valve sizes (p < 0.001). No severe patient-prosthesis mismatch (effective orifice area index < or = 0.65 cm2/m2) could be observed. CONCLUSIONS: After 1 year, the Medtronic Advantage valve shows comparable transvalvular mean pressure gradients across the valve sizes used during rest and exercise. This is accompanied by a significant left ventricular mass regression, an important indicator for long-term survival.

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study.

BACKGROUND: Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. METHODS: Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. RESULTS: Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. CONCLUSIONS: Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.

Automatic patient registration for port placement in minimally invasive endoscopic surgery.

Optimal port placement is a delicate issue in minimally invasive endoscopic surgery, particularly in robotically assisted surgery. A good choice of the instruments' and endoscope's ports can avoid time-consuming consecutive new port placement. We present a novel method to intuitively and precisely plan the port placement. The patient is registered to its pre-operative CT by just moving the endoscope around fiducials, which are attached to the patient's thorax and are visible in its CT. Their 3D positions are automatically reconstructed. Without prior time-consuming segmentation, the pre-operative CT volume is directly rendered with respect to the endoscope or instruments. This enables the simulation of a camera flight through the patient's interior along the instruments' axes to easily validate possible ports.

A comparative analysis of outcome after heart transplantation in patients aged 60 years and older: the University of Alberta experience.

BACKGROUND: The Registry of the International Society for Heart and Lung Transplantation (ISHLT) 2001 Annual Report indicated that the vast majority of heart transplant recipients are between 50 and 64 years of age. However, patient age beyond 60 years may have higher long-term mortality compared to younger patients. The purpose of this study was to compare short- and intermediate-term results including rates of acute rejection, transplant coronary artery disease, infections, malignancy, and mortality in cardiac transplant recipients 60 years or older with those below the age of 60 years. METHODS: We retrospectively analyzed the results of 50 patients aged 60 years and older who underwent heart transplantation at the University of Alberta from January 1990 to December 2000 and compared them with the results of 225 younger patients undergoing heart transplantation in the same time period. RESULTS: The older and younger groups had similar rates for treated acute rejection episodes (20.0% vs. 12.6%), transplant coronary artery disease (4.0% vs. 1.1%), and mortality (10.5% vs. 14.3%), respectively. No differences were noted with regards to quality and quantity of infection or malignancy rates. Five-year actuarial survival between the older and younger patients was also comparable at 89.5% vs.86.9% (p > 0.05). CONCLUSIONS: Heart transplantation in patients 60 years of age and older can be performed as successfully as in younger patients (< 60 years) with comparable morbidity and mortality, suggesting that patient age per se should not be an exclusion criterion for heart transplantation.