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PURPOSE OF REVIEW Ventricular assist device (VAD) therapy is currently one of the fastest-developing fields in cardiac surgery. Consistently improved technology, research, and gain of clinical experience have established VADs as an important option for the treatment of congestive heart failure. During the past year, novel devices and less invasive surgical procedures have been revolutionizing this field. The purpose of this manuscript is to review these innovations with special emphasis on device-related surgery. RECENT FINDINGS Device miniaturization has enabled less invasive VAD surgery, excluding the need for full sternotomy. Recent data show that intrahospital survival rates following less invasive VAD implantation are surpassing 90%. Secondly, two new devices, Heartmate 3 and MVAD, are being applied and tested for clinical application. In this context, the Heartmate 3 CE mark study recently concluded with excellent outcomes and without any pump thrombosis or device malfunctions. SUMMARY The first clinical results of the newest generation of VADs are very promising compared with old-generation devices. Furthermore, less invasive surgery is becoming a standard for the implantation, exchange, or explantation of left VADs. The joint venture of improved technology and innovative surgical techniques will push this field forward to even better outcomes and reduced complication rates.

Objective This study investigated the use of 2 Synergy Micro-Pumps for full biventricular assist device (BiVAD) support. We examined right-sided and left-sided hemodynamic parameters over a range of right-sided and left-sided pump speeds in an acute, fibrillating, non-beating-heart model in sheep. Methods Five juvenile sheep (43 ± 2 kg) were implanted with two Synergy Micro-Pumps (CircuLite Inc, Saddle Brook, NJ), 1 in the right (RV) and 1 in the left ventricle (LV), through a median sternotomy. The RVAD outflow graft was anastomosed end-to-side to the pulmonary artery and the LVAD outflow to the ascending aorta. After surgical implantation of both pumps, ventricular fibrillation was induced and hemodynamic parameters were measured at 9 different levels of RVAD pump speed (from 20,000 to 28,000 rpm at 1,000-rpm increments), while the speed of the LVAD was set constant at 24,000, then at 26,000, and finally, at 28,000 rpm. Results At a fixed LVAD speed, RVAD and LVAD flow both increased identically as RVAD speed was increased. This was due to redistribution of blood volumes that resulted in resetting of pressure gradients across each pump and each vascular bed in a manner dictated by the pump pressure–flow characteristics. Results were similar with LVAD set at 24,000, 26,000, or 28,000 rpm. At the highest LVAD and RVAD speeds, flow averaged 3.1 ± 0.7 liters/min, and pressures in the right atrium, pulmonary artery, left atrium, and aorta averaged 2.2 ± 3.7, 24.4 ± 6.5, 22.4 ± 5.5, and 56.6 ± 8.5 mm Hg, respectively. Conclusion BiVAD support with the 2 Synergy Micro-Pumps is feasible and able to provide full hemodynamic support in sheep. This approach holds promise for providing biventricular partial support in humans and, in particular, for full support in small adults and children.

Background We investigated predictive factors of postoperative recurrence of mitral regurgitation (MR) after mitral valve annuloplasty for functional ischemic MR. Methods This study was a retrospective review of patients with functional MR who underwent mitral ring annuloplasty at our institution from 1998 to 2008. Records were reviewed for perioperative variables, including echocardiographic measurements. Recurrence was defined as MR grade moderate (3+) or greater on any postoperative echocardiogram. Results Of 548 patients who underwent mitral annuloplasty for functional MR, echocardiogram reports were available for review for 250. These patients comprised the study cohort. There were 154 patients with concomitant coronary artery bypass grafting. The left ventricular (LV) end-diastolic (LVED) index was calculated by dividing the LVED dimension by body surface area (BSA). A high LVED index (> 3.5 cm/m 2 ) was predictive of MR recurrence ( p = 0.047): the recurrence rate was 20.3% (13 of 64) in high-index patients and 10.2% (19 of 186) in low-index ( 2 ) patients. Median recurrence-free survival was 35 months (range, 19 to 59 months) in high-LVED-index patients and 46.5 months (range, 22 to 75 months) in low-LVED-index patients ( p = 0.048). Preoperative MR severity and LV ejection fraction were not predictive of MR recurrence. Conclusions Careful analysis of the preoperative echocardiogram using a novel, easily calculated variable, the LVED index, may help identify patients who are at greater risk for MR recurrence and reduced survival. Such information could prompt consideration of alternative or additional interventions in these patients.

Reoperations on dysfunctional aortic homografts often require root reconstruction with coronary reanastomosis. This is associated with substantial perioperative morbidity and mortality. Resecting compromised aortic homograft valve leaflets and seating a new valve within the homograft annulus avoids root reconstruction and is a viable alternative.We retrospectively evaluated 50 patients undergoing reoperations on dysfunctional homografts between 1999 and 2011. Outcomes were compared between valve-in-valve (ViV) and aortic valve-prosthetic conduit (AVR-C) procedures.Twenty-eight patients underwent ViV, and 22 had AVR-C. Groups were similar in age, sex, and incidence of endocarditis and renal failure. Median time between homograft and index procedure was 8.5 years for AVR-C and 8 years for ViV patients (p=0.93). Patients undergoing AVR-C had longer cardiopulmonary bypass (282 versus 151 minutes; p0.001) and cross-clamp (207 versus 106 minutes; p0.001) times and received significantly more intraoperative red blood cell transfusions than ViV patients (36.4% versus 7.1%; p=0.014). Patients undergoing ViV had shorter intensive care unit stays (47 hours versus 67 hours for AVR-C; p=0.049) and fewer postoperative red blood cell transfusions (21.4% versus 54.5%; p=0.020). There were trends toward shorter ventilation times for ViV patients (6 hours versus 11 hours for AVR-C; p=0.077), shorter postoperative length of stay (7 days versus 9 days; p=0.092), and fewer readmissions (3.6% versus 19.0%; p 0.073). One operative mortality occurred in the AVR-C group.The strategy of replacing aortic valve leaflets in a failed calcified homograft, with a valve seated inside the annulus, is a safe alternative to root reconstruction. Preserving root architecture and coronary buttons facilitates shorter cardiopulmonary bypass and cross-clamp times, and directly impacts transfusions, intensive care unit time, hospital stay, and readmission rates.

Yirmi yil once sol femoropopliteal bypass ameliyati gecirmis 38 yasinda kadin hasta sol uylugunda sisme yakinmasi ile basvurdu. Implant yapilan ven grefti yanindaki sis bolgede anevrizma tespit edildi ve komplikasyon olmadan tamir edildi. Ameliyat ayrintilari olgu sunumunda aciklanmistir. Anah tar soz cuk ler: Aneurysm; femoropopliteal baypas; vena saphena magna. A 38-year-old female patient who underwent a left femoropopliteal bypass surgery 20 years ago admitted with swelling of the left thigh. In the swollen region adjacent to the implanted vein graft, an aneurysm was noted and repaired without complications. The details of the operation are delineated in the following case report.

The postoperative course after major surgical procedures such as cardiothoracic operations is often accompanied by acute metabolic abnormalities due to large volume and temperature shifts. In general, those intervention-induced trauma might cause the use of catecholamines to stabilize hemodynamics. Within the cardiac community, there are still controversial discussions about standardized medical therapy to treat postoperative acidosis, for example, buffering versus nonbuffering for improving catecholaminergic response of myocardial contractility. The aim of this study was to investigate the influence of mild (and thus clinically relevant) acidosis on myocardial contractility and catecholamine response in explanted trabeculae of ovine hearts. Intact trabeculae (n = 24) were isolated from the right ventricle of healthy sheep hearts. Two different groups (group 1: pH = 7.40, n = 9 and group 2: pH = 7.20, n = 13) were investigated, and force amplitudes were measured at frequencies between 30 and 180 beats per minute and increasing catecholamine concentrations (isoprenaline 0-3 × 10(-6) mM). Force-frequency relation experiments in the presence of a physiological and/or mild acidotic pH solution showed no significant differences. Mean force amplitudes normalized to the lowest frequency showing no significant differences in force development between 0.5 and 3 Hz (n = 9 vs. 13, P = n.s.) (0.5 Hz absolute values 3.1 ± 2.6 for pH = 7.40 vs. 3.8 ± 2.6 mN/mm(2) for pH = 7.20, P = n.s.). Moreover, there was no significant difference in relaxation kinetics between the two groups. Furthermore, the experiments showed similar catecholamine responses in both groups. Force amplitudes normalized to baseline and maximum force showed no significant differences in force development between baseline and maximum isoprenaline concentrations (n = 6 vs. 9, P = n.s.) (baseline absolute values 4.3 ± 4.0 for pH = 7.40 vs. 3.9 ± 1.2 mN/mm(2) for pH = 7.20, P = n.s.). Additionally, relaxation kinetics did not show differences after catecholamine stimulation. The presented experiments revealed no significant negative inotropic effects on isometrically contracting ovine trabeculae with mild metabolic acidosis (pH = 7.2) compared with physiological pH (7.4). Additionally, similar catecholamine responses were seen in both groups. Further investigations (e.g., in vivo and/or in failing hearts with reduced compensatory reserves) will be necessary to examine optimal medical treatment for metabolic abnormalities after cardiac surgery.

Cooling before circulatory arrest or ischemic arrest has been reported to influence myocardial performance in isolated neonatal hearts. The aim of the present study was to analyze indices of myocardial contractility and relaxation in an in vivo neonatal model after deep hypothermic circulatory arrest (DHCA). DHCA (18°C; DHCA group; n = 8) or mild hypothermic cardiopulmonary bypass ([MH-CPB] 32°C; MH-CPB group; n = 10) was applied in newborn piglets. After reperfusion (60 and 120 min), left ventricular dP/dt(max) increased in DHCA and MH-CPB, while-dP/dt(max) decreased slightly in DHCA and increased in MH-CPB. Nevertheless, the differences between the two groups did not reach statistical significance. In conclusion, left ventricular contractility remained stable after reperfusion following DHCA, to some degree at the expense of the diastolic function.

A 53-year-old Caucasian male suffering from idiopathic dilated cardiomyopathy underwent cardiac transplantation. Fifty-seven days following transplant, he developed posttransplant lymphoproliferative disorder (PTLD), which was Epstein-Barr virus positive. The initial episode of PTLD was treated with a dose reduction in cyclosporine (CsA) and a 4-week course of rituximab. Subsequent biopsies showed resolution of PTLD. One year posttreatment, his evaluation revealed severe cardiac allograft vasculopathy (CAV). The patient was switched to sirolimus-based immunosuppression regimen with gradual up-titration of sirolimus in combination with complete withdrawal of previously administered Calcineurin-based immunosuppression approach. The switchover was carried out over a 6-week period. In the following 3 years, there was CAV regression as well as PTLD remission, without any significant episode of rejection. Despite frequent relapses with this form of PTLD, the patient remains in remission, 8 years posttransplantation. In summary, sirolimus has been demonstrated to attenuate the progression of CAV, and this case report illustrates that regression of CAV is possible. In addition to preventing rejection, mammalian target of rapamycin inhibitors directly suppress signaling pathways leading to PTLD and may be effective monotherapy for preventing rejection and suppressing PTLD.

Epidemiologic studies have revealed an annual incidence of congestive heart failure in the United States and Europe of 0.3% to 1.0% [1]. In cardiovascular research, large animal models are necessary to examine the pathophysiology and surgical treatments of heart failure. Although a large variety of animal models to study acute heart failure exist, valuable models on the effects of ventricular assist devices in chronic heart failure (CHF) are scarce. These models have been created depending on the specific scientific question, as well as on factors such as accessibility, reproducibility, ethical, and financial considerations. To study pathophysiologic processes, such as the development of heart failure or how mechanical unloading by ventricular assist devices can induce reverse remodeling, animal models should closely mimic the human clinical findings. We reviewed the existing literature and summarized various large animal models of CHF with particular focus on the advantages and disadvantages of each model.

Lipid-apheresis (LA) is thought to improve microcirculation. However, limited data are available on the effects on peripheral microcirculation. We investigated upper limb microcirculation of 22 patients undergoing regular LA on a weekly basis before and after LA. Using standardized semiquantitative scales, we analyzed blood flow, vasomotor function, and erythrocyte aggregation by capillary microscopy. In addition, capillary blood flow in quiescence and under heat and cryo-stress was evaluated by photoplethysmographic and laser Doppler anemometry. Moreover, levels of vasoactive mediators adrenalin, noradrenalin, endothelin-1 (ET-1), atrial natriuretic peptide (ANP), asymmetrical dimethyl-arginine (ADMA), as well as total protein and fibrinogen were measured. We found a significant increase in blood flow, the number of perfused capillaries and an improvement of erythrocyte aggregation by capillary microscopy. Using laser Doppler anemometry, we were able to show that this increase was predominantly located in the superficial layer capillaries (Δ44.53 ± 135.81%, n.s.) and less so in deeper layer arterioles (Δ2.75 ± 24.84%, n.s.). Vascular response to heat and cryo stress was also improved after LA but failed to reach significance. LA significantly reduced levels of epinephrin (-33 ± 39.2%), ANP (-28.8 ± 20.2%), ADMA (-74.1 ± 23%), and fibrinogen (-45.4 ± 19.7%) when comparing before LA and after LA values. In summary, we found an improvement in the microcirculation of the upper limbs under LA, which may result from a decrease of vasoconstrictors, improvement of vasomotor function, and a decrease in blood viscosity or erythrocyte aggregation.

Objective: The present paper exemplary describes several severe stenoses of supraaortic branches with its symptoms and operative treatments.Methods: Eight patients, two female (68 ± 5 y), six male (73 ± 4 y), were retrospectively evaluated. Patients showed neurological signs as followed: recurring attacks of vertigo (80%), temporary paresis of extremity (20%), speech disorders (20%) and subclavian and/or carotic-steel-syndrome (15%). Seven patients have already been previously treated with revascularization of the supraaortic branches in the past. The surgical techniques used were thrombendarterectomy of the internal carotid artery, carotid-subclavian bypass and complex aorto-truncal, aorto-carotid and aorto-subclavian-bypass.Results: One patient died nine days postoperatively due to myocardial infarction. Mean duration of stay on intensive care unit was 1.5 days. Mean duration of postoperative ventilation was six hours. Average duration of stay on normal ward was nine days.Conclusion: This study presents several complex reconstructions of supraaortic branches, which were indicated in cases with severe stenoses of supraaortic branches. Even though treatment strategies were complex the peri- and postoperative complication rates are quite low. These therapeutic strategies were necessary to avoid severe neurological complications in these patients.

Objective Cellular and mechanical treatment to prevent heart failure each holds therapeutic promise but together have not been reported yet. The goal of the present study was to determine whether combining a cardiac support device with cell-based therapy could prevent adverse left ventricular remodeling, more than either therapy alone. Methods The present study was completed in 2 parts. In the first part, mesenchymal stem cells were isolated from rodent femurs and seeded on a collagen-based scaffold. In the second part, myocardial infarction was induced in 60 rats. The 24 survivors were randomly assigned to 1 of 4 groups: control, stem cell therapy, cardiac support device, and a combination of stem cell therapy and cardiac support device. Left ventricular function was measured with biweekly echocardiography, followed by end-of-life histopathologic analysis at 6 weeks. Results After myocardial infarction and treatment intervention, the ejection fraction remained preserved (74.9-80.2%) in the combination group at an early point (2 weeks) compared with the control group (66.2-82.8%). By 6 weeks, the combination therapy group had a significantly greater fractional area of change compared with the control group (69.2% ± 6.7% and 49.5% ± 6.1% respectively, P = .03). Also, at 6 weeks, the left ventricular wall thickness was greater in the combination group than in the stem cell therapy alone group (1.79 ± 0.11 and 1.33 ± 0.13, respectively, P = .02). Conclusions Combining a cardiac support device with stem cell therapy preserves left ventricular function after myocardial infarction, more than either therapy alone. Furthermore, stem cell delivery using a cardiac support device is a novel delivery approach for cell-based therapies.

Functional mitral regurgitation (MR) is a common clinical entity which will likely increase in the future due to predicted demographic changes. It is also associated with poor long-term survival. The anatomic structure of the mitral valve apparatus is complex and consists of several components, each of which can be affected by a variety of diseases resulting in MR. In primary MR, the valvular incompetence is caused by compromised or structurally disrupted components of the valve apparatus; the valve in functional MR is structurally normal, with the regurgitation resulting from failure of coaptation of the mitral valve leaflets without coexisting structural changes of the valve itself. Therefore, we defined functional MR as a systolic retrograde flow from the left ventricle into the left atrium due to reduction and/or elimination of the normal systolic coaptation of the mitral valve leaflets. A slow progression of the symptoms is typical for this valve disease and often ends in irreversible left ventricular dysfunction. The pathophysi- ology and treatment of functional MR are quite complex. This article reviews and summarizes the existing literature, with a focus on the pathophysiology and current treatment of functional MR.

Several genetic polymorphisms have been identified to play a role in the occurrence and progression of renal dysfunction after cardiac surgery with cardiopulmonary bypass (CPB). Recently, it was demonstrated that the T allele of SNP rs1617640 in the promoter of the erythropoetin (EPO) gene is significantly associated with proliferative diabetic retinopathy (PDR) and end-stage renal disease (ESRD) due to increased EPO expression. This disease risk-associated gene and its potential pathway mediating severe microvascular complications in T-allele carriers could also play a role on renal dysfunction in patients who underwent cardiac surgery with CPB. We hypothesized that the patients' ability to produce increased EPO concentrations will affect morbidity and mortality after CPB. We conducted a prospective single center study between April 2006 and May 2007. In 481 patients who underwent cardiac surgery with CPB we prospectively examined the SNP rs1617640 in the promoter of the EPO gene by DNA sequencing. The patients were grouped according to their genotype (GG, GT, and TT). The genotype distribution of SNP rs1617640 in the promoter of the EPO gene was 36% (TT), 49% (TG), and 15% (GG). There was no difference in age, body mass index, gender, CPB time, or length of stay in intensive care unit. The hospitalization was irrespective of the patients' genotypes. The baseline creatinine in the TT group was 0.2 points higher than in the other groups; however this was without statistical significance in the multivariate analysis. No significant difference was shown in Euroscore, the Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation Score II, Acute Renal Failure Score, or the Risk, Injury, Failure, Loss of Kidney Function Score. The mortality was equal across the genotypes. However, an association between the TT genotype and acute renal replacement therapy (P=0.03), intra-aortic balloon pump usage (P=0.02), and serum creatine phosphokinase-MB increase (P=0.03) were observed after cardiac surgery. Our analysis suggests that the risk allele (T) of rs1617640 plays a role in the development of renal dysfunction after cardiac surgery with CPB. Patients with the TT risk allele required more frequent acute renal replacement therapy. Since our result is close to the border of significance, this hypothesis should be investigated in larger prospective studies with long-term follow-up to emphasize this polymorphism as a potential risk factor.

Drowning and near-drowning is often associated with severe hypothermia requiring active core rewarming.We performed rewarming by cardiopulmonary bypass(CPB). Between 1987 and 2007, 13 children (9 boys and 4 girls) with accidental hypothermia were rewarmed by extracorporeal circulation (ECC) in our institution. The average age of the patients was 3.2 years. Resuscitation was started immediately upon the arrival of the rescue team and was continuously performed during the transportation.All patients were intubated and ventilated. Core temperature at admission ranged from 20 to 29°C (mean 25.3°C). Connection to the CPB was performed by thoracic (9 patients) or femoral/iliac means (4 patients). Restoration of circulation was achieved in 11 patients (84.6%). After CPB termination two patients needed an extracorporeal membrane oxygenation system due to severe pulmonary edema.Five patients were discharged from hospital after prolonged hospital stay. During follow-up, two patients died(10 and 15 months, respectively) of pulmonary complications and one patient was lost to follow-up. The two remaining survivors were without neurological deficit.Modes of rewarming, age, sex, rectal temperature, and serum electrolytes did not influence mortality. In conclusion,drowning and near-drowning with severe hypothermia remains a challenging emergency. Rewarming by ECC provides efficient rewarming and full circulatory support.Although nearly half of the children may survive after rewarming by ECC, long-term outcome is limited by pulmonary and neurological complications.

Adenosine monophosphate – activated kinase (AMPK) plays a key role in the coordination of the hearts anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α- subunit (63kDa), a regulating β - subunit (38kDa) and a γ- subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ – subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.

Ventricular assist device (VAD) support inpatients with a prosthetic heart valve had previously been considered a relative contraindication due to an increased risk of thromboembolic complications. We report our clinical experience of VAD implantation in patients with prosthetic heart valves, including both mechanical and bioprosthetic valves. The clinical records of 133 consecutive patients who underwent VAD implantation at a single institution from January 2002 through June 2009 were retrospectively reviewed. Six of these patients had a prosthetic valve in place at the time of device implantation. Patient demographics,operative characteristics, and postoperative complications were reviewed.Of the six patients,four were male.The mean age was 57.8 years (range 35–66 years). The various prosthetic cardiac valves included a mechanical aortic valve (n = 2), a bioprosthetic aortic valve (n = 3), and a mechanical mitral valve (n = 1).The indications for VAD support included bridge to transplantation (n = 2), bridge to recovery (n = 1), and postcardiotomy ventricular failure(n = 3). Three patients underwent left ventricular assist device placement and three received a right ventricular assist device. Postoperatively, standard anticoagulation management began with a heparin infusion (if possible)followed by oral anticoagulation.The 30-day mortality was50% (3/6). The mean duration of support among survivors was 194.3 days (range 7–369 days) compared with 16.0 days(range 4–29 days) for nonsurvivors. Of the three survivors,two were successfully bridged to heart transplantation and one recovered native ventricular function.Among the three nonsurvivors,acute renal failure developed in each case, and two developed heparin-induced thrombocytopenia. This study suggests that VAD placement in patients with a prosthethic heart valve, either mechanical or bioprosthetic,appears to be a reasonable option.

We established a stable and reproducible animal model of chronic heart failure (CHF) in sheep to investi- gate biomolecular changes. Therefore, two biomarkers, adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial growth factor-A (VEGF-A) were examined to reveal their role during chronic ischemic conditions of the heart. AMPK was studied because it plays an important role in cellular energy homeostasis and its upregulation is associated with myocardial ischemia, whereas VEGF-A was studied because it acts as an important signaling protein for neo- angiogenesis. We examined 15 juvenile sheep (mean weight, 78 4 kg; control, n = 3; ShamOP, n = 2; coronary microembolization (CME), n = 10). CHF was induced under fluoroscopic guidance by multiple sequential micro- embolizations (MEs) through bolus injection of polysterol microspheres (90 mm, n = 25.000) into the left main coro- nary artery. CME was repeated up to three times at 2- to 3-week intervals until animals started to develop stable signs of CHF. All animals were followed for 3 months. Phosphorylation of AMPK, marking the activated protein form, was detected by Western blotting. VEGF-A and vas- cular endothelial growth factor-receptor 2 (VEGF-R2) mRNA were detected by real-time polymerase chain reaction. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was used as a reference housekeeping gene. All 10 CHF animals developed clinical signs of CHF as indicated by a significant decrease of cardiac output, decreased ejection fraction, as well as occurrence of tachy- cardia and tachypnoea. Western blots showed significant phosphorylation of AMPK in CME animals compared to the control group (phospho-adenosine monophosphate- activated protein kinase a) (GAPDH control: 0.0, CME left ventricle (LV): 0.39 0.20, CME right ventricle (RV): 0.53 0.30; P < 0.05). VEGF-A and VEGF-R2 expression in CME animal myocardium was within the range of the control group, but this data did not reach statistical signifi- cance due to the small size of this group. While microinjec- tion was performed into the left main coronary artery, phosphorylation of AMPK and expression of VEGF-A and VEGF-R2 were significantly higher in the RV than in the LV. Multiple sequential intracoronary MEs can effec- tively induce myocardial dysfunction with clinical and bio- molecular signs of chronic ischemic cardiomyopathy. Quantitative analysis of biomolecular markers showed a significantly higher phosphorylation of AMPK in CHF animals compared with control myocardium.

To assess the current status of the prevalence and variability of internal mammary graft use in contemporary multivessel coronary artery bypass graft (CABG).The internal mammary artery (IMA) is considered the gold-standard conduit in coronary artery bypass graft (CABG) surgery. There is universal agreement that the IMA graft is associated with significantly improved short-term and long-term survival in CABG and the use of the IMA is recognized as a key performance measure world wide. In the recently developed Society of Thoracic Surgeons (STS) composite measure for CABG, use of an IMA was found to be the only intra-operative performance measure associated with quality of care. Furthermore, several studies have shown that bilateral IMA (BIMA) use improves long-term outcome compared with single IMA use. An objective assessment of surgical quality is essential to improve surgical outcomes.There is strong evidence that IMA graft use is associated with significantly improved short-term and long-term survival in CABG. In spite of this, the prevalence of IMA grafting is less than expected. Moreover, there is a large variability in IMA use by hospital. There are also disparities in IMA use by sex and race, which should be addressed in the interest of expanding the benefits of IMA grafting to the maximum possible number of patients. Although the frequency of IMA use in CABG procedures seems to increase each year, further actions are necessary at the individual clinician, institutional, and political levels to improve quality of care.

Rationale: Heart failure (HF) is known to be associated with increased Ca 2+ /calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKIIδ expression in end-stage failing human hearts (dilated and ischemic cardiomyopathy) and the functional effects of CaMKII inhibition on contractility. Methods and Results: Expression analysis revealed that CaMKIIδ, both cytosolic δ C and nuclear δ B splice variants, were significantly increased in both right and left ventricles from patients with dilated or ischemic cardiomyopathy versus nonfailing. Experiments with isometrically twitching trabeculae revealed significantly improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca 2+ loading. This was confirmed in isolated myocytes by a reduced SR Ca 2+ spark frequency and hence SR Ca 2+ leak, resulting in increased SR Ca 2+ load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca 2+ leak, was found to be markedly reduced in KN-93–treated trabeculae. Interestingly, CaMKII inhibition did not influence contractility in nonfailing sheep trabeculae. Conclusions: The present study shows for the first time that CaMKII inhibition acutely improves contractility in human HF where CaMKIIδ expression is increased. The mechanism proposed consists of a reduced SR Ca 2+ leak and consequently increased SR Ca 2+ load. Thus, CaMKII inhibition appears to be a possible therapeutic option for patients with HF and merits further investigation.

Hyperhidrosis (primary or secondary) describes a disorder of excessive sweating. It has a significant negative impact on quality of life and affects nearly 1% of the population living in the United Kingdom (UK). Axillary involvement is the most common affecting 80% of cases. A common link to these disorders is an extreme non-thermoregulatory sympathetic stimulus of exocrine sweat glands, mostly due to emotional stimuli. Non-surgical treatment involves topical medication, iontophoresis and systemic anti-cholinergics. More recently the use of intradermal botulinum toxin has gained popularity. Surgical treatment reserved for severe cases, not responding to conservative management involves local excision, curettage and thoracoscopic sympathectomy. Evolving concepts for treatment, risks and benefits are discussed in the paper herein.

Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.).

Minimally-invasive approaches have become increasingly important in cardiac valve surgery. Smaller incisions have become commonplace in many major centers. We reviewed the existing literature and present the current state-of-the-art of minimally-invasive valve operations in this paper.

Objectives: We investigated changes in Na+currents (INa) in permanent (or chronic) atrial fibrillation (AF) and the effects of INainhibition using ranolazine (Ran) on arrhythmias and contractility ...

The optimal treatment of congenital aortic valve lesions is a controversial issue. This study was performed to evaluate the outcome after surgical treatment of aortic valve lesions in congenital aortic valve disease. Between the years of 2000 and 2008, 61 patients (mean age: 12.6 +/- 9.6 years, range: 1 day to 40 years) underwent aortic valve surgery for congenital aortic valve disease. Twenty-four patients had undergone previous cardiovascular operations. Indications for surgery were aortic regurgitation in 14.7% (n = 9), aortic stenoses in 26.2% (n = 16), and mixed disease in 59.1% (n = 36). The Ross procedure was performed in 37.7% (n = 23), aortic valve replacement with biological or mechanical prostheses in 29.5% (n = 18). Concomitant procedures were performed in 91.8% (n = 56) due to associated congenital cardiac defects. The overall mortality rate was 5%. Six patients needed reoperation. Implantation of permanent pacemakers occurred in six patients for permanent atrioventricular block. At the latest clinical evaluation, all survivors are in New York Heart Association class I-II and are living normal lives. Aortic valve surgeries in patients with congenital heart disease have had low mortality and morbidity rates in our series. Surgical technique as well as timing should be tailored for each patient. Aortic valve replacement should be delayed until the implantation of an adult-sized prosthesis is possible.

Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 +/- 2 kg), chronic heart failure was induced under fluoroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 microm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan-Ganz catheter (mean pulmonary arterial pressure [PAP mean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 +/- 4 bpm [base] to 93 +/- 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 +/- 5 [base] to 38 +/- 7 [3 mo][P < 0.05]), and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.

Due to improved outcome after surgery for congenital heart defects, children, adolescents, and grown-ups with congenital heart defects become an increasing population. In order to evaluate operative risk and early outcome after mechanical aortic valve replacement (AVR) in this population, we reviewed patients who underwent previous repair of congenital heart defects. Between July 2002 and November 2008, 15 (10 male and 5 female) consecutive patients (mean age 14.5 +/- 10.5 years) underwent mechanical AVR. Hemodynamic indications for AVR were aortic stenosis in four (27%), aortic insufficiency in eight (53%), and mixed disease in three (20%) after previous repair of congenital heart defects. All patients had undergone one or more previous cardiovascular operations due to any congenital heart disease. Concomitant cardiac procedures were performed in all of them. In addition to AVR, in two patients, a mitral valve exchange was performed. One patient received a right ventricle-pulmonary artery conduit replacement as concomitant procedure. The mean size of implanted valves was 23 mm (range 17-29 mm). There were neither early deaths nor late mortality until December 2008. Reoperations were necessary in five (33%) and included implantation of a permanent pacemaker due to complete atrioventricular block in two (15%), mitral valve replacement with a mechanical prosthesis due to moderate to severe mitral regurgitation in one (7%), aortocoronary bypass grafting due to stenosis of a coronary artery in one (7%), and in one (7%), a redo subaortic stenosis resection was performed because of a secondary subaortic stenosis. At the latest clinical evaluation, all patients were in good clinical condition without a pathological increased gradient across the aortic valve prosthesis or paravalvular leakage in echocardiography. Mechanical AVR has excellent results in patients after previous repair of congenital heart defects in childhood, even in combination with complex concomitant procedures. Previous operations do not significantly affect postoperative outcome.

When a left ventricular aneurysm leads to pulmonary congestive symptoms, aneurysmectomy may provide relief. This retrospective study included 269 patients who underwent aneurysmectomy between 1993 and 2002, by the classic Cooley operation in 164 and by Dor ventriculoplasty in 105. There were no significant differences in early and late survival between groups, although the frequency of extended anteroseptal infarction was higher in patients undergoing the Dor procedure. Postoperative echocardiographic findings showed significant improvements in left ventricular function in both groups, in terms of end-diastolic and end-systolic dimensions and ejection fraction. Left ventricular aneurysmectomy significantly improved the clinical status and hemodynamic parameters of symptomatic patients. The choice of surgical technique depends on the extent of the scar segment, especially the presence of an anteroseptal scarred area. The Dor procedure is more suitable for restoring normal left ventricular geometry in patients with extensive septal infarction.

Objective: Renal dysfunction is one of the most serious complications following cardiac surgery with cardiopulmonary bypass. The causes of renal dysfunction following cardiac surgery are poorly understood. We hypothesised that T-786C endothelial NO synthase (eNOS) polymorphism may lead to an increase in the occurrence of postoperative renal dysfunction following cardiac surgery with cardiopulmonary bypass. Methods: A total of 497 patients undergoing cardiac surgery with cardiopulmonary bypass were included in the study. The T-786C eNOS polymorphism was detected by a polymerase chain reaction. The patients were grouped on the basis of whether they were homozygous or heterozygous for the C allele (TC + CC; n = 289) or only homozygous for the T allele (TT; n = 208). Results: No significance was demonstrated in the preoperative risk factors, with the exclusion of smoking habits (p = 0.04) for the C-allele carrier. The administration of anti-lipid agents (p = 0.01) and antiarrhythmics (p = 0.01) was significantly lower in the TC/CC group. The TC + CC genotype group had a significantly greater decrease in creatine clearance(p = 0.024),the lowest creatine clearance(p = 0.004) and moreC-allelecarriersreceived acuterenal replacement therapy (p = 0.04). The usage of norepinephrine (p = 0.02) and dobutamine (p = 0.02) was significantly higher in C-allele carriers. In the TC + CC genotype group, cross-clamp time (p = 0.02) and administration of red cell transfusion (p = 0.04) achieved statistically significant difference. The overall inhospital mortality rate was 8.2% for all patients and was not significant between genotypes. Conclusions: The present findings support the hypothesis that the T-786C eNOS polymorphism may play a role in the development of renal dysfunction and increase the occurrence of renal replacement therapy following cardiac surgery with cardiopulmonary bypass. This polymorphism may be useful in stratifying the risk for the development of postoperative renal dysfunction. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 μM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 μM; developed tension −9.8 ± 2.5% compared to control group; P

Background: Current concepts of acute pulmonary embolism suggest that right ventricular (RV) dilatation and failure are the consequence of pressureoverload-inducedRVhypoperfusionandischemia.Methods:Sixteenhuman-sizedhybridpigswereinstrumented forthemeasurementof RVand aortic pressure, aortic and right coronary artery blood flow (RCA BF), RVoxygen consumption (RV MVO2) and RV free wall segment length. The pulmonary artery was constricted (PAC) to increase RV peak pressure acutely 2.5-fold (from 27 2t o 64 3 mmHg, n = 9), and the constriction was maintained for 6 h. Results: At 10 min after PAC, a RV work index (RVWI, RV pressure-segment length loops) was increased 2.3fold, indicating an initial RV adaptation to increased afterload. At 1 h, 3 h and 6 h after PAC, however, RVWI decreased progressively towards control levels, while RCA BF and RV MVO2 continued to increase. The arterial-coronary venous pH difference did not increase throughout the protocol. Arterial troponin Tconcentration increased from 0.08 0.03 to 0.80 0.20 ng/ml at 6 h after PAC. None of the parameters changed in control animals (n = 7). Conclusion: We conclude that in our model RV failure during PAC develops in spite of increased coronary blood flow and MVO2. Thus, mechanisms different from ischemia may contribute to progressive RV failure after pulmonary embolism. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Die obstruktive Form der hypertrophen Kardiomyopathie ist eine Erkrankung des Myokards, die eine dynamische systolische Stenosierung des linksventrikularen Ausflusstrakts bewirkt. Bei symptomatischen Patienten und/oder erheblichem Druckgradienten uber der Ausflussbahn ist die chirurgische Therapie indiziert und beseitigt sicher und nachhaltig die Stenose. Die Myektomie erfolgt dabei von transaortal und wird durch Zuhilfenahme eines scharfen Dreizinkerhakens exakt definiert. Die Erweiterung der Myektomie nach lateral und intraventrikular schafft einen sicheren Zugang zum subvalvularen Mitralklappenapparat. Durch Mobilisation und Teilexzision der Papillarmuskeln wird deren Anteposition aufgehoben und sowohl die systolische Vorwartsbewegung des anterioren Mitralklappensegels als auch die begleitende Mitralklappeninsuffizienz beseitigt. Die guten Ergebnisse mit ausgesprochen geringer Komplikationsrate sowie Mortalitat bei hervorragenden funktionellen Langzeitergebnissen geben der chirurgischen Therapie heute gegenuber der weit verbreiteten Technik einer alkoholischen Septalablation weiterhin den Status eines Goldstandard.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Indirect evidence from clinical trials demonstrates that chronic inhibition of the renin–angiotensin-system (RAS) significantly reduces the incidence of AF. Since mechanisms of this protective effect of RAS-blockade are poorly understood, we directly tested proarrhythmic effects of angiotensin II (Ang II) in human atrial myocardium. Methods: Isolated trabeculae from human atrial appendages (n = 80) were electrically stimulated. We assessed isometric force and incidence of arrhythmic extra contractions (AECs) with and without increasing concentrations of Ang II (1–1000 nmol/L) in the absence or presence of receptor-blockade by saralasin (non-specific ATR-antagonist), irbesartan (AT1R-antagonist) or PD123319 (AT2R-antagonist). Results: Twitch force and AECs concentration-dependently increased with Ang II. Effects became significant at concentrations >1 nmol/L Ang II and were maximal at 1000 nmol/L (increase in twitch force to 157±14% and AECs from 0 to 80%) saralasin and irbesartan partially prevented the inotropic effect of 100 nmol/L Ang II (by 4±12% and 68±6%; p

Endothelin is the most potent endogenous vasoconstrictor and is involved in several vascular disorders such as arterial hypertension. Its intense interaction with other vasoactive hormone systems revealed the consideration about the endothelin gene as an interesting candidate for influencing the development of essential hypertension and hypertensive endorgan damage. The purpose of this study was to investigate the role of endothelin-1 Lys198Asn polymorphism in patients with severe arterial hypertension as well as associated endorgan damages.In 400 hypertensive patients and 150 normotensive controls we examined the endothelin-1 Lys198Asn polymorphism by DNA sequencing and patients were divided according to their genotype (GG, GT, and TT). Moreover, the frequency of endothelin-1 Lys198Asn polymorphism was investigated with respect to the prevalence of several actual or historical endorgan damages (renal disorder, coronary artery disease, vascular events, vascular damage, and congestive heart failure) in hypertensive patients.Genotype distribution for endothelin-1 Lys198Asn polymorphism was 57.3% (GG), 41.3% (GT), and 1.43% (TT) in normotensive individuals; and in hypertensive individuals was 54.75% (GG), 43% (GT) and 2.25% (TT). Genotype distribution was unaffected in patients with severe hypertension, renal disorder, vascular events, vascular damage, and congestive heart failure. We, however, found a significant difference in hypertensive individuals with coronary artery disease and TT genotype (P=0.004).Homozygous TT carrier contributes to a higher prevalence of coronary artery disease, especially for three-vessel disease in hypertensive individuals. Thus, the polymorphism at position 198 could serve as a possibility to differentiate high-risk subgroups in the heterogeneous population of hypertensive patients.

Nous avons etudie les donnees concernant 21 malades traites par perfusion selective des deux arteres renales par 500 mL d'une solution a 8°c d'histidine-tryptophane-cetoglutarate (HTC) pour chacune des arteres renales comme protection renale au cours de la chirurgie aortique. Seules les donnees concernant la chirurgie aortique avec clampage obligatoire de l'aorte supra-renale pour des anevrysmes de l'aorte abdominale juxta ou supra-renale (AAA) ou des syndromes de Leriche associes a une stenose des arteres renales sont presentees. Cinq malades ont eu une chirurgie d'urgence en raison d'une rupture de l'AAA. Les 16 autres malades ont ete traites electivement. Dans trois cas (14%) une stenose des arteres renales etait diagnostiquee. Cependant, la mise en place d'un pontage aorto-renal a ete necessaire chez 7 malades. En tout, 14 pontages aorto-renaux ont ete implantes (5 greffes veineuses et 9 protheses). Quatre (19%) des malades ont necessite des catecholamines pour etablir des conditions circulatoires stables. Chez deux (9%) de ces malades, une ischemie colique a ete observee et une sigmoidectomie realisee. Chacun de ces quatre malades a eu une chirurgie immediate et l'un d'eux est decede en post-operatoire en raison d'un sepsis severe. Dans quatre cas une insuffisance renale post-operatoire a ete observee. Trois de ces malades avaient ete admis pour une chirurgie d'urgence en raison de leur situation hemodynamique due a une rupture de l'AAA. Aucun malade n'a necessite une hemodialyse chronique post-operatoire. Alors que chez tous les malades ayant eu une chirurgie elective la fonction renale est restee stable comme indique par les taux de creatininemie post-operatoire, chez 5 des 7 malades ayant eu un pontage aorto-renal, la fonction renale s'est amelioree. La perfusion par une solution froide d'HTC offre une methode additionnelle pour proteger la fonction renale chez les malades ayant une chirurgie elective comportant un clampage de l'aorte supra-renale.

Examinamos los datos de 21 pacientes que fueron tratados mediante perfusion selectiva de ambas arterias renales con 500 ml de una solucion de histidina-triptofano-cetoglutarato (HTK) a 8 °C para la proteccion renal durante la cirugia aortica. Solamente se presentan los resultados de las cirugias aorticas en las que fue inevitable el clampaje de aorta suprarrenal para el tratamiento de los aneurismas aorticos abdominales (AAA) yuxtarrenales o suprarrenales o el sindrome de Leriche alto con estenosis de las arterias renales. Cinco pacientes fueron sometidos a cirugia inmediata debido a la rotura de un AAA; en los 16 pacientes restantes la cirugia fue programada. En 3 casos (14%) se diagnostico estenosis de las arterias renales; no obstante, fue necesario colocar un bypass aortorrenal en 7 pacientes. En total se colocaron 14 bypass aortorrenales (5 injertos venosos y 9 implantes protesicos). Cuatro pacientes (19%) necesitaron la administracion de catecolaminas para estabilizar las condiciones circulatorias; en 2 de estos casos (9%) se observo isquemia adicional del colon y se realizo una sigmoidectomia. Estos 4 pacientes fueron sometidos a una cirugia inmediata y 1 fallecio tras la intervencion debido a una sepsis grave. En 4 casos se observo insuficiencia renal postquirurgica. Tres de estos pacientes fueron ingresados para una cirugia de urgencia a causa de su situacion hemodinamica por la perforacion del AAA. Ninguno de los pacientes necesito dialisis cronica tras la cirugia. Si bien la funcion renal permanecio estable en todos los pacientes que fueron sometidos a una cirugia programada, a juzgar por las concentraciones sericas de creatinina, la funcion mejoro en 5 de 7 pacientes sometidos a cirugia de bypass aortorrenal. La perfusion con una solucion fria de HTK constituye un proceso adicional que protege la funcion renal en los pacientes sometidos a cirugia programada con clampaje suprarrenal de aorta.

We evaluated the newly developed miniaturized HIA microdiagonal blood pump (MDP) as a continuous flow left ventricular assist device. In a sheep model (n = 6), the MDP was implanted through left lateral thoracotomy and placed paracorporeally with inflow conduit to left atrium and outflow conduit to descending aorta. The sheep were pumped at a mean flow rate of 2.5 L/min for 7 days. Anticoagulation was applied by intravenous heparin administration. Postoperatively, activated clotting time was held stable with values of 200 seconds. During follow-up, blood samples (creatinine kinase, creatinine, glutamic-oxaloacetic transaminase (aspartate aminotransferase) (GOT), glutamate dehydrogenase (GLDH), gamma-GT, plasma-free hemoglobin, and hemoglobine) were taken daily. After 7 days, the sheep were killed for macroscopic examination. Systemic artery pressures remained stable during the whole test period. Because of operative reasons, the hemoglobin value (7.5 +/- 0.61 g/dl) decreased perioperatively, but recovered within the test period, whereas creatinine kinase increased initially after thoracotomy, but decreased to normal within days. Renal and liver functions were slightly impaired perioperatively, indicated by temporarily enhanced values of GOT, gamma-GT, GLDH, and creatinine. The MDP did not produce significant hemolysis as measured by plasma-free hemoglobin levels. Wound infections did not occur. We conclude that the MDP ran successfully as an left ventricular assist device for 7 days in sheep has potential for long-term support, and may serve as an alternative to current technologies. Presented data were not obtained in a clinical trial; however, the results are promising enough to proceed with longer duration animal studies.

In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR-Ca(2+) leak at the time of LVAD implantation (HF-Im) and heart transplantation (HF-Tx) and evaluated the effects of CaMKII-inhibition. Human left-ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR-Ca(2+) loading and scanned for diastolic Ca(2+) sparks (confocal microscopy). In HF-Im, the high diastolic spark frequency (CaSpF) of 0.76 ± 0.12 × 100 μm(-1) × s(-1) could be reduced to 0.48 ± 0.10 × 100 μm(-1) × s(-1) by CaMKII inhibition (AIP, 1 μM). The amplitude of Ca(2+) sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR-Ca(2+) leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF-Tx, we detected an even higher CaSpF of 1.00 ± 0.10 100 μm(-1) × s(-1) and a higher SR-Ca(2+) leak compared with HF-Im (increase by 81 ± 33%, n cells/patients = 156/7 vs. 130/7, P 0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 ± 0.09 100 μm(-1) × s(-1,) P = 0.06) and significantly reduced spark duration (n sparks/patients = 58/3 vs. 159/3, P 0.05). Conclusively, the SR-Ca(2+) leak was reduced by 69 ± 12% in HF-Tx upon CaMKII inhibition (n cells/patients = 53/3 vs. 91/3, P 0.05). These data show that the SR-Ca(2+) leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR-Ca(2+) leak in HF-Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation.

In der vorgestellten Kasuistik wird das Auftreten einer spontanen Kreislaufstabilisierung nach vorherigem Kreislaufstillstand ohne durchgefuhrte Reanimationsmasnahmen bei einem Patienten mit Herzschrittmacher vorgestellt. In der Literatur wird diese Situation bei primar durchgefuhrter, aber erfolgloser Reanimation als „Lazarus-Phanomen“ bezeichnet. Es kam intraoperativ zu einem Kreislaufstillstand, der nach Entschluss der beteiligten Arzte nicht behandelt wurde. Nach 6 min ohne Beatmung konnte eine spontane Kreislaufstabilisierung beobachtet werden. Die Operation wurde daraufhin fortgefuhrt und zielgerichtet beendet. Im Anschluss an die Operation wurde der Patient auf die Intensivstation aufgenommen. Er verstarb dort 2 Tage spater, ohne einen adaquaten Bewusstseinszustand wiedererlangt zu haben. Die Pathomechanismen fur das Auftreten des „Lazarus-Phanomens“ sind unklar. In der aktuellen Literatur werden verschiedene Mechanismen und multifaktorielle Geschehen als Ursache fur dieses Phanomen diskutiert.

Venöse Aneurysmata der großen Gefäße stellen anatomische Raritäten dar. Die meisten bisher publizierten Malformationen des venösen Systems betreffen hauptsächlich die Vena cava inferior und treten in unterschiedlichen Formen auf. Aussackungen der infradiaphragmalen Vena cava inferior werden bei routinemäßig durchgeführten abdominellen Sonographien nur selten beobachtet und stellen dann häufig Zufallsbefunde dar. Berichte hierüber beschränken sich auf einzelne Kasuistiken und bereiten den Klinikern nicht selten diagnostische und therapeutische Schwierigkeiten. In der vorliegenden Arbeit wird eine asymptomatische, ausgeprägte venöse trunkuläre Missbildung der Vena cava inferior mit suprarenaler Abflussstörung beschrieben. Der hier vorgestellte Fall stellt einen bislang nicht beschriebenen Befund dar. Unter Berücksichtigung der gesamten Befundkonstellation entschlossen wir uns zu einer konservativen Behandlung des Patienten.

OBJECTIVES The Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated multicentre, prospective, single-arm database established to collect post-Conformite Europeenne Mark clinical information on patients receiving the HeartWare® Ventricular Assist System (HVAD®). The number of patients requiring longer periods of mechanical circulatory support is ever increasing and so further investigation into long-term outcomes in bridge-to-transplant populations is necessary. METHODS Data were collected on 254 commercial implants performed between February 2009 and March 2012 from nine centres in Europe (7 centres) and Australia (2 centres). Patients were followed to device explant, heart transplant or death, and the outcomes of patients who remained on support longer than 2 years were analysed. Summary statistics were used to describe patient demographics, adverse events, length of support and outcomes for this long-term cohort. RESULTS A total of 124 patients (49% of the original ReVOLVE population) were on support for more than 2 years (range: 731-2108 days), 76 of whom are still alive on support. Overall survival through 5 years was 59%. CONCLUSIONS Owing to the low rate of heart transplants, a significant number of patients receiving a left ventricular assist device as a bridge to transplant remain on support for prolonged periods, often exceeding 2, 3 and even 4 years. Real-world use of the HVAD system continues to show excellent outcomes for patients on the device, including those on support beyond 2 years.

The importance of mechanical circulatory support in the therapy of advanced heart failure is steadily growing. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the assist devices, providing increased pump durability and prolonged patient survival. The HeartWare left ventricular assist device system (HeartWare Inc., Framingham, MA, USA) is a mechanical ventricular assist device with over 8000 implantations worldwide. Compared with other available assist devices it is smaller in size and used in a broad range of patients. The possibility of minimally invasive procedures is one of the major benefits of the device – allowing implants and explants, as well as exchanges of the device with reduced surgical impact. We present here a review of the existing literature on the treatment of advanced heart failure using the HeartWare left ventricular assist device system.

The therapy of terminal heart failure with left ventricular assist devices has become a standard in cardiac surgery. Yet the surgical implantation technique is not standardized and differs from center to center. Complications associated with left ventricular assist device (LVAD) inflow cannula placement are thrombosis, suction events, and flow disturbances. Within this in vitro study we aimed to investigate if the fixation technique of the sewing ring has an impact on the position of the inflow cannula. For this in vitro study the HeartMate III LVAD (Thoratec Corporation, Pleasanton, CA, USA) was used. In five sessions, two approaches were considered for coring of the ventricle for LVAD inflow cannula insertion: "sew-then-core" and "core-then-sew." In the "sew-then-core" technique, the sewing cuff is first affixed to the heart, usually with 8-16 interrupted pledgeted mattress sutures. Subsequently, a cylindrical knife is used to resect a cylindrical core of myocardium to permit cannula insertion. In the "core-then-sew" technique, the sequence is reversed such that the knife is used before the suture ring is affixed. When the "sew-then-core" technique is used, the mattress sutures may be placed with full-thickness bites that penetrate the endocardium (i.e., transmural stitching) or partial-thickness bites that do not penetrate the endocardium (i.e., epicardial stitching). When the "core-then-sew" technique is used, the suture is passed fully into the ventricular lumen and fed back through the cored hole, at which point the needle may be reinserted into the freshly cored myocardium such that it exits the epicardium (i.e., transmural stitching with back stitch) or not (i.e., transmural stitching without back stitch). These four different sewing ring fixation suturing techniques were tested by experienced surgeons to affix the sewing ring: transmural stitching, epicardial stitching, transmural stitching with back stitch, and transmural stitching without back stitch. The sewing ring was sewed onto a silicone dummy designed to simulate the left ventricle with standard 2-0 Ethibond sutures (Ethicon, Somerville, NY, USA). Afterward, the dummies were measured and documented via photography. In addition, porcine hearts were used to simulate the suturing techniques in a physiological setting. The setting of the inflow cannula is substantially influenced by the fixation method of the sewing ring. Epicardial stitching showed the best results with stable cannula fixation, minimal gap around the cannula and no contact between the sutures and sewing ring with blood. The method of transmural stitching without back stitch showed the worst results by creating the biggest epithelial gap between inflow cannula and tissue as well as proving the biggest surface for blood contact between sewing ring and sutures. In general, both "sew-then-core" techniques resulted in a greater degree of apposition between the cuff and epicardial tissue. Within the study we revealed that the surgical fixation of the sewing ring has a significant impact on the inflow cannula stability, position, and tissue apposition in LVAD implantation surgery. Epicardial stitching of the sewing ring provides the best results in order to prevent suction events as well as thrombosis formation.

Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 10

OBJECTIVES Ventricular blood stasis is a concern for continuous flow mechanical support devices and might contribute to the formation of thromboembolic events. The HeartWare® Ventricular Assist System (HVAD®) is equipped with the Lavare™ cycle that is a periodic speed modulation feature designed to alter flow patterns within the left ventricle and reduce areas of potential blood stasis. Here, we report in vitro and clinical findings on the effects of the Lavare cycle. METHODS The effect of pump speed changes on the intraventricular flow field was examined with an in vitro particle image velocimetry model. The clinical impact of the Lavare cycle was evaluated through a retrospective review of the ReVOLVE study which includes 248 patients implanted with the HVAD following Conformite Europeenne Mark in nine centres in Europe and Australia. Baseline characteristics, adverse event profiles and Kaplan-Meier survival estimates were stratified by patients using/not using the Lavare cycle. RESULTS Particle image velocimetry showed increased ventricular washout with an active Lavare cycle as measured by the fluid velocities and angular dispersion parameters. With the Lavare cycle on, there was also a 22% decrease in the stagnation index compared with when the Lavare cycle was off. In the ReVOLVE registry, patients with the Lavare cycle turned on (n = 215) were supported for 497 patient-years, whereas patients who did not use the speed modulation (n = 33) were supported for 39.3 patient-years. The Lavare cycle did not significantly affect patient survival as both groups had approximately an 80% survival after 1 year. Patients using the Lavare cycle had significantly fewer rates of stroke [0.06 vs 0.20 events per patient-year (EPPY), P = 0.0008], sepsis (0.03 vs 0.15 EPPY, P = 0.0003) and right heart failure (0.03 vs 0.18 EPPY, P < 0.0001) with no difference in the transplant or recovery rates among the two cohorts. CONCLUSIONS The Lavare cycle effectively generates ventricular washout and the adverse event profiles of ReVOLVE patients with the Lavare cycle on were better than those with the Lavare cycle off. Larger studies are warranted to verify the positive effect of the Lavare cycle and to optimize speed modulation settings, so additional clinically relevant improvements can be realized.

The effects of isoflurane on the determinants of blood flow during Coronary Artery Bypass Graft (CABG) surgery are not completely understood. This study characterized the influence of isoflurane on the diastolic Pressure-Flow (P-F) relationship and Critical Occlusion Pressure (COP) during CABG surgery. Twenty patients undergoing CABG surgery were studied. Patients were assigned to an isoflurane or control group. Hemodynamic and flow measurements during CABG surgery were performed twice (15 minutes after the discontinuation of extracorporeal circulation (T15) and again 15 minutes later (T30)). The zero flow pressure intercept (a measure of COP) was extrapolated from a linear regression analysis of the instantaneous diastolic P-F relationship. In the isoflurane group, the application of isoflurane significantly increased the slope of the diastolic P-F relationship by 215% indicating a mean reduction of Coronary Vascular Resistance (CVR) by 46%. Simultaneously, the Mean Diastolic Aortic Pressure (MDAP) decreased by 19% mainly due to a decrease in the systemic vascular resistance index by 21%. The COP, cardiac index, heart rate, Left Ventricular End-Diastolic Pressure (LVEDP) and Coronary Sinus Pressure (CSP) did not change significantly. In the control group, the parameters remained unchanged. In both groups, COP significantly exceeded the CSP and LVEDP at both time points. We conclude that short-term application of isoflurane at a sedative concentration markedly increases the slope of the instantaneous diastolic P-F relationship during CABG surgery implying a distinct decrease with CVR in patients undergoing CABG surgery.