Najbolji izbor – kako izabrati odgovarajući uređaj?

An increasing number of patients suffering from end-stage heart failure require VAD implantation as either a bridge-to-transplantation or destination therapy. The choice of the right device depends upon the medical urgency; the need of uni- or biventricular support; the duration of support expected; and the institutional availability. Patients with multi-organ failure and unclear neurological situation can be supported with rotary pumps/ECMO first, and in case of recovery, a paracorporeal system can be connected to the previously implanted cannulas. In stable patients qualifying for left ventricular support, an intracorporeal system of the second generation can be implanted, allowing freedom of movement for 6-8 hours before recharging becomes necessary, and support intervals exceeding 1 year. Restrictions are given by the need of high-dose anticoagulation and a certain complication rate, especially in the first 3 months (bleeding, thromboembolism, infection, mechanical failure). The survival rate after the primary LVAD implantation is 74 % after 12 months and 55 % after 24 months; this is significantly better than the survival rate after RVAD, BVAD or TAH.Sve veći broj pacijenata u terminalnoj fazi zatajivanja srca zahtijevaju ugradnju mehaničke potpore srcu i cirkulaciji, kao premoštenje do transplantacije srca ili kao destinacijska terapija. Odabir odgovarajućeg uređaja ovisi o kliničkom stanju pacijenta, potrebi za jednostrukom ili dvostrukom ventrikularnom potporom, očekivanom trajanju ugrađene potpore i mogućnostima institucije. Pacijentima s multi organskim zatajenjem i nejasnim neurološkim smetnjama može se prvo ugraditi rotacijska pumpa/ECMO, te u slučaju oporavka., parakorporalni uređaj može biti povezan s ranije implantiranim kanilama. Kod stabilnih pacijenata, predodređenih za ugradnju potpore lijevom ventriklu, moguće je ugraditi intrakorporalni uređaj druge generacije, koji dozvoljava slobodno kretanje 6-8 sati do punjenja baterija i podupire intervale preko jedne godine. Ograničenja nastaju zbog potrebe za visokim dozama antikoagulacijske terapije i pojave određenih komplikacija, posebno u prva tri mjeseca nakon implantacije (krvarenje, tromboembolija, infekcija, mehaničke nepravilnosti). Stopa preživljenja 12 mjeseci nakon ugradnje LVAD-a je 74% i 55% nakon 24 mjeseca što je značajno bolje nego preživljenje nakon ugradnje RVAD, BVAD or TAH

Dangerous surgical scavenger hunt: the complicated course of a patient with left ventricular assist device and end-stage renal disease undergoing reconstructive flap surgery

Patients with left ventricular assist devices (LVADs) who develop stage IV sacral pressure sores (SPS) have an increased procedural risk. We present the complications, including severe intra- and postoperative bleeding, diarrhea with metabolic acidosis, volume loss and acute on chronic renal failure, flap dehiscence and late LVAD outflow cannula thrombosis, in a 54-year-old male who underwent diverting ileostomy (DI) and subsequent fasciocutaneous flap (FCF) surgery for stage IV SPS while supported with an LVAD. Our experience suggests that, despite continuous heparinization, life-threatening thrombotic complications, such as device clotting, can occur. Therefore, the benefit of intervention has to outweigh the risk of bleeding, which should be managed with meticulous surgical technique and substitution of red blood cells rather than the reversal of heparinization or the substitution of clotting factors. Continuation of double anti-platelet therapy should also be considered

Wound healing gene-family expression differences between fetal and foreskin cells used for bioengineered skin substitutes

For tissue engineering, several cell types and tissues have been proposed as starting material. Allogenic skin products available for therapeutic usage are mostly developed with cell culture and with foreskin tissue of young individuals. Fetal skin cells offer a valuable solution for effective and safe tissue engineering for wounds due to their rapid growth and simple cell culture. By selecting families of genes that have been reported to be impli- cated in wound repair and particularly for scarless fetal wound healing including transforming growth factor-beta (TGF-b) superfamily, extracellular matrix, and nerve/angiogenesis growth factors, we have analyzed differences in their expression between fetal skin and foreskin cells, and the same passages. Of the five TGF-b superfamily genes analyzed by real-time reverse transcription–polymerase chain reaction, three were found to be signifi- cantly different with sixfold up-regulated for TGF-b2, and 3.8-fold for BMP- 6 in fetal cells, whereas GDF-10 was 11.8-fold down-regulated. For nerve growth factors, midkine was 36-fold down-regulated in fetal cells, and pleiotrophin was 4.76-fold up-regulated. We propose that fetal cells present technical and therapeutic advantages compared to foreskin cells for effective cell-based therapy for wound management, and overall differences in gene expression could contribute to the degree of efficiency seen in clinical use with these cells

Development of a complex intervention to improve participation of nursing home residents with joint contractures: a mixed-method study

Joint contractures in nursing home residents limit the capacity to perform daily activities and restrict social participation. The purpose of this study was to develop a complex intervention to improve participation in nursing home residents with joint contractures

Minimized extracorporeal circulation is improving outcome of coronary artery bypass surgery in the elderly

Advanced age is a known risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). Minimized extracorporeal circulation (MECC) has been shown to reduce the negative effects associated with conventional extracorporeal circulation (CECC). This trial assesses the impact of MECC on the outcome of elderly patients undergoing CABG. Eight hundred and seventy-five patients (mean age 78.35 years) underwent isolated CABG using CECC (n=345) or MECC (n=530). The MECC group had a significantly shorter extracorporeal circulation time (ECCT), cross-clamp time and reperfusion time and lower transfusion needs. Postoperatively, these patients required significantly less inotropic support, fewer blood transfusions, less postoperative hemodialysis and developed less delirium compared to CECC patients. In the MECC group, intensive care unit (ICU) stay was significantly shorter and 30-day mortality was significantly reduced [2.6% versus 7.8%; p<0.001]. In conclusion, MECC improves outcome in elderly patients undergoing CABG surgery

Empagliflozin inhibits Na + /H + exchanger activity in human atrial cardiomyocytes

Aims Recent clinical trials have proven gliflozins to be cardioprotective in diabetic and non-diabetic patients. However, the underlying mechanisms are incompletely understood. A potential inhibition of cardiac Na+/H(+)exchanger 1 (NHE1) has been suggested in animal models. We investigated the effect of empagliflozin on NHE1 activity in human atrial cardiomyocytes. Methods and results Expression of NHE1 was assessed in human atrial and ventricular tissue via western blotting. NHE activity was measured as the maximal slope of pH recovery after NH(4)(+)pulse in isolated carboxy-seminaphtarhodafluor 1 (SNARF1)-acetoxymethylester-loaded murine ventricular and human atrial cardiomyocytes. NHE1 is abundantly expressed in human atrial and ventricular tissue. Interestingly, compared with patients without heart failure (HF), atrial NHE1 expression was significantly increased in patients with HF with preserved ejection fraction and atrial fibrillation. The largest increase in atrial and ventricular NHE1 expression, however, was observed in patients with end-stage HF undergoing heart transplantation. Importantly, acute exposure to empagliflozin (1 mu mol/L, 10 min) significantly inhibited NHE activity to a similar extent in human atrial myocytes and mouse ventricular myocytes. This inhibition was also achieved by incubation with the well-described selective NHE inhibitor cariporide (10 mu mol/L, 10 min). Conclusions This is the first study systematically analysing NHE1 expression in human atrial and ventricular myocardium of HF patients. We show that empagliflozin inhibits NHE in human cardiomyocytes. The extent of NHE inhibition was comparable with cariporide and may potentially contribute to the improved outcome of patients in clinical trials

Left ventricular support adjustment to aortic valve opening with analysis of exercise capacity

Background LVAD speed adjustment according to a functioning aortic valve has hypothetic advantages but could lead to submaximal support. The consequences of an open aortic valve policy on exercise capacity and hemodynamics have not yet been investigated systematically. Methods Ambulatory patients under LVAD support (INCOR®, Berlin Heart, mean support time 465 ± 257 days, average flow 4.0 ± 0.3 L/min) adjusted to maintain a near normal aortic valve function underwent maximal cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC) at rest and during constant work rate exercise (20 Watt). Results Although patients (n = 8, mean age 45 ± 13 years) were in NYHA class 2, maximum work-load and peak oxygen uptake on CPET were markedly reduced with 69 ± 13 Watts (35% predicted) and 12 ± 2 mL/min/kg (38% predicted), respectively. All patients showed a typical cardiac limitation pattern and severe ventilatory inefficiency with a slope of ventilation to carbon dioxide output of 42 ± 12. On RHC, patients showed an exercise-induced increase of mean pulmonary artery pressure (from 16 ± 2.4 to 27 ± 2.8 mmHg, p < 0.001), pulmonary artery wedge pressure (from 9 ± 3.3 to 17 ± 5.3 mmHg, p = 0.01), and cardiac output (from 4.7 ± 0.5 to 6.2 ± 1.0 L/min, p = 0.008) with a corresponding slight increase of pulmonary vascular resistance (from 117 ± 35.4 to 125 ± 35.1 dyn*sec*cm−5, p = 0.58) and a decrease of mixed venous oxygen saturation (from 58 ± 6 to 32 ± 9%, p < 0.001). Conclusion An open aortic valve strategy leads to impaired exercise capacity and hemodynamics, which is not reflected by NYHA-class. Unknown compensatory mechanisms can be suspected. Further studies comparing higher vs. lower support are needed for optimization of LVAD adjustment strategies

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT0064175

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

A proposal for early dosing regimens in heart transplant patients receiving thymoglobulin and calcineurin inhibition

There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation