Can mechanical circulatory support be an effective treatment for HFpEF patients?

Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and represents approximately 50% of all heart failure (HF) patients. Patients with this complex clinical scenario, characterized by high filling pressures, and reduced cardiac output (CO) associated with progressive multi-organ involvement, have so far not experienced any significant improvement in quality of life or survival with traditional HF treatment. Left ventricular assist devices (LVAD) have offered a new treatment alternative in terminal heart failure patients with reduced ejection fraction (HFrEF), providing a unique combination of significant pressure and volume unloading together with an increase in CO. The small left ventricular cavity in HFpEF patients challenges left-sided pressure unloading, and new anatomical entry points need to be explored for mechanical pressure and volume unloading. Optimized and pressure/volume-adjusted mechanical circulatory support (MCS) devices for HFrEF patients may conceivably be customized for HFpEF anatomy and hemodynamics. We have developed a long-term MCS device for HFpEF patients with atrial unloading in a pulsed algorithm, leading to a significant reduction of filling pressure, maintenance of pulse pressure, and increase in CO demonstrated in animal testing. In this article, we will discuss HFpEF pathology, hemodynamics, and the principles behind our novel MCS device that may improve symptoms and prognosis in HFpEF patients. Data from mock-loop hemolysis studies, acute, and chronic animal studies will be presented.

Predictors of long intensive care need after lung transplantation.

BACKGROUND: While expected need for intensive care after lung transplantation (LTx) does not normally affect organ allocation, it would be useful to estimate whether intensive care capacity is limited. The aim of this study was to assess factors available before LTx to identify predictors of prolonged intensive care unit (ICU) length of stay (LOS) after LTx. METHODS: All bilateral LTx recipients excluding re-transplantation and multi-organ transplantation at Oslo University Hospital from 2000 to 2013 were included (n = 277). Predictive factors for ICU LOS were identified using pre- and perioperative variables. RESULTS: Univariate analyses showed that recipients with pulmonary arterial hypertension, young age, female gender, low body height, low pretransplant actual total lung capacity (aTLC), and recipients who received an oversized donor lung were at risk for long ICU LOS. Patients with emphysema had lower risk of long ICU LOS. In multivariate analyses, a lower aTLC (p < .001) and a higher mean pulmonary artery pressure (mPAP) (p = .004) predicted prolonged ICU LOS. CONCLUSIONS: We found that small recipient lung volume and high mPAP were predictors for prolonged ICU LOS. Our observations may be useful in planning use of resources in LTx, particularly in times of limited intensive care resources.

The Predictive Value of Depression in the Years After Heart Transplantation for Mortality During Long-Term Follow-Up.

OBJECTIVE: Current understanding of the prognostic impact of depression on mortality after heart transplantation (HTx) is limited. We examined whether depression after HTx is a predictor of mortality during extended follow-up. Subsequently, we explored whether different symptom dimensions of depression could be identified and whether they were differentially associated with mortality. METHODS: Survival analyses were performed in a sample of 141 HTx recipients assessed for depression, measured by self-report of depressive symptoms (Beck Depression Inventory - version 1A [BDI-1A]), at median 5.0 years after HTx, and followed thereafter for survival status for up to 18.6 years. We used uni- and multivariate Cox proportional hazard models to examine the association of clinically significant depression (BDI-1A total score ≥10), as well as the cognitive-affective and the somatic subscales of the BDI-1A (resulting from principal component analysis) with mortality. In the multivariate analyses, we adjusted for relevant sociodemographic and clinical variables. RESULTS: Clinically significant depression was a significant predictor of mortality (hazard ratio = 2.088; 95% confidence interval = 1.366-3.192; p = .001). Clinically significant depression also was an independent predictor of mortality in the multivariate analysis (hazard ratio = 1.982; 95% confidence interval = 1.220-3.217; p = .006). The somatic subscale, but not the cognitive-affective subscale, was significantly associated with increased mortality in univariate analyses, whereas neither of the two subscales was an independent predictor of mortality in the multivariate analysis. CONCLUSIONS: Depression measured by self-report after HTx is associated with increased mortality during extended follow-up. Clinical utility and predictive validity of specific depression components require further study.

Continuous-flow LVADs in the Nordic countries: complications and mortality and its predictors.

OBJECTIVES: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries. DESIGN: This was a retrospective, international, multicenter cohort study. RESULTS: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p < .001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively. CONCLUSION: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.

Hypothermia elongates the contraction-relaxation cycle in explanted human failing heart decreasing the time for ventricular filling during diastole.

Targeted temperature management is part of the standardized treatment for patients in cardiac arrest. Hypothermia decreases cerebral oxygen consumption and induces bradycardia; thus, increasing the heart rate may be considered to maintain cardiac output. We hypothesized that increasing heart rate during hypothermia would impair diastolic function. Human left ventricular trabeculae obtained from explanted hearts of patients with terminal heart failure were stimulated at 0.5 Hz, and contraction-relaxation cycles were recorded. Maximal developed force (Fmax), maximal rate of development of force [(dF/d t)max], time to peak force (TPF), time to 80% relaxation (TR80), and relaxation time (RT = TR80 - TPF) were measured at 37, 33, 31, and 29°C. At these temperatures, stimulation frequency was increased from 0.5 to 1.0 and to 1.5 Hz. At 1.5 Hz, concentration-response curves for the ß-adrenergic receptor (ß-AR) agonist isoproterenol were performed. Fmax, TPF, and RT increased when temperature was lowered, whereas (dF/d t)max decreased. At all temperatures, increasing stimulation frequency increased Fmax and (dF/d t)max, whereas TPF and RT decreased. At 31 and 29°C, resting tension increased at 1.5 Hz, which was ameliorated by ß-AR stimulation. At all temperatures, maximal ß-AR stimulation increased Fmax, (dF/d t)max, and maximal systolic force, whereas resting tension decreased progressively with lowering temperature. ß-AR stimulation reduced TPF and RT to the same extent at all temperatures, despite the more elongated contraction-relaxation cycle at lower temperatures. Diastolic dysfunction during hypothermia results from an elongation of the contraction-relaxation cycle, which decreases the time for ventricular filling. Hypothermic bradycardia protects the heart from diastolic dysfunction and increasing the heart rate during hypothermia should be avoided. NEW & NOTEWORTHY Decreasing temperature increases the duration of the contraction-relaxation cycle in the human ventricular myocardium, significantly reducing the time for ventricular filling during diastole. During hypothermia, increasing heart rate further reduces the time for ventricular filling and in some situations increases resting tension further impairing diastolic function. Modest ß-adrenergic receptor stimulation can ameliorate these potentially detrimental changes during diastole while improving contractile force generation during targeted temperature management.

Measurement of gaseous microemboli in the prime before the initiation of cardiopulmonary bypass.

INTRODUCTION: The use of cardiopulmonary bypass is associated with a risk of neurocognitive deficit caused by gaseous microemboli. Flushing the empty bypass circuit with carbon dioxide, which is more soluble than air, may reduce the amount of gaseous microemboli in the priming solution before the initiating of cardiopulmonary bypass. METHOD: We measured the amount of gaseous microemboli in twenty primed bypass circuits. Ten circuits were flushed with carbon dioxide before being primed and ten circuits were non-flushed. All circuits in both groups were primed with crystalloid priming. An ultrasonic clinical bubble counter was used to count gaseous microemboli in the prime for 20 minutes. RESULTS: The median numbers of gaseous microemboli counts were highest during the first minute in both groups, with a significantly lower median value in the group flushed with carbon dioxide (397.5) versus the non-flushed group (1900). In the 20th minute, the median values of gaseous microemboli were significantly lower (p<0.023) in the flushed (0.5) versus non-flushed (10.75) groups. The gaseous microembolic count in the flushed group remained lower than in the non-flushed group when tested minute by minute throughout the whole 20-minute period. CONCLUSION: Flushing the bypass circuits with carbon dioxide before priming significantly decreased the number of gaseous microemboli in the priming solution.

Cognitive function after heart transplantation: Comparing everolimus-based and calcineurin inhibitor-based regimens.

BACKGROUND: Studies have shown conflicting results concerning the occurrence of cognitive impairment after successful heart transplantation (HTx). Another unresolved issue is the possible differential impact of immunosuppressants on cognitive function. In this study, we describe cognitive function in a cohort of HTx recipients and subsequently compare cognitive function between subjects on either everolimus- or calcineurin inhibitor (CNI)-based immunosuppression. METHODS: Cognitive function, covering attention, processing speed, executive functions, memory, and language functions, was assessed with a neuropsychological test battery. Thirty-seven subjects were included (everolimus group: n=20; CNI group: n=17). The extent of cerebrovascular pathology was assessed with magnetic resonance imaging. RESULTS: About 40% of subjects had cognitive impairment, defined as performance at least 1.5 standard deviations below normative mean in one or several cognitive domains. Cerebrovascular pathology was present in 33.3%. There were no statistically significant differences between treatment groups across cognitive domains. CONCLUSIONS: Given the high prevalence of cognitive impairment in the sample, plus the known negative impact of cognitive impairment on clinical outcome, our results indicate that cognitive assessment should be an integrated part of routine clinical follow-up after HTx. However, everolimus- and CNI-based immunosuppressive regimens did not show differential impacts on cognitive function.

Cognitive function among long-term survivors of heart transplantation.

BACKGROUND: Cognitive impairment is documented early after heart transplantation (HTx), but we lack data on cognitive function beyond the fourth year post-transplant. Against the background of good long-term survival, this knowledge is necessary to improve clinical care throughout the entire post-transplant period. METHODS: We assessed cognitive function with a neuropsychological test battery in a sample of HTx recipients ≥16 years post-transplant. To improve clinical utility, we also applied adapted consensus criteria for Mild Cognitive Impairment (MCI). Furthermore, we explored sociodemographic and clinical characteristics possibly related to cognitive function. RESULTS: Thirty-seven subjects were included 20.3 (±3.8) years after HTx. Mean age was 57.5 (±14.2) years, and 18.9% were women. Up to 38.9% exhibited impaired test performance (ie, performance at least 1.5 standard deviations below the normative mean) on several individual cognitive measures, especially on measures of processing speed, executive functions, memory, and language functions. One subject was diagnosed with dementia, and 30.1% qualified for MCI. Those with MCI had lower hemoglobin than those without. CONCLUSIONS: A substantial proportion of long-term survivors of HTx might be cognitively impaired. The level of impairment appears comparable to what is defined as MCI in the literature. Modifiable factors related to cognitive impairment might exist.

Improved Detection Of Thromboembolic Complications In Left Ventricular Assist Device By Novel Accelerometer-Based Analysis.

We have previously demonstrated that accelerometer-based vibration analysis detects thromboembolism and pump thrombosis in HeartWare Left Ventricular Assist Device (HVAD) using the third harmonic frequency (pump_speedx3). Thromboembolism also affected the amplitude of the nonharmonic frequencies. The aim of this study was to determine whether nonharmonic-amplitude (NHA) analysis can improve the diagnosis of thromboembolic complications. An accelerometer was attached to HVAD in three in vitro and seven in vivo experiments. Control interventions, including load and pump speed alternations (n = 107), were followed by thromboembolic events (n = 60). A sliding fast-Fourier-transform was analyzed, and changes in NHAs were quantified in the acute phase and in a steady state. Receiver operating characteristic curves were constructed with cutoff values of NHA to detect thromboembolic events. Positive predictive values were calculated on the basis of a specificity of 1. In the acute phase, NHA change was 6.5 times higher under thromboembolism than under control interventions (p < 0.001). Most thromboembolic events lead to concomitant changes in both NHA and third-harmonic amplitude. Combining the two methods improved the PPV by 8.3%. At steady state, signal changes predominantly demonstrated either NHA or third-harmonic changes. Combined signal analysis improved the PPV by 36%. This method enhanced the detection of thromboembolism and pump thrombosis in the HVAD.

Obesity and outcomes after left ventricular assist device implantation: insights from the EUROMACS Registry.

OBJECTIVES: The objective was to analyse associations between obesity and outcomes after left ventricular assist device (LVAD) implantation. METHODS: A retrospective analysis of the EUROMACS Registry was performed. Adult patients undergoing primary implantation of a continuous-flow LVAD between 2006 and 2019 were included (Medtronic HeartWare® HVAD®, Abbott HeartMate II®, Abbott HeartMate 3™). Patients were classified into 4 different groups according to body mass index at the time of surgery (body mass index <20 kg/m2: n = 254; 20-24.9 kg/m2: n = 1281; 25-29.9 kg/m2: n = 1238; ≥ 30 kg/m2: n = 691). RESULTS: The study cohort was comprised of 3464 patients. Multivariable Cox proportional cause-specific hazards regression analysis demonstrated that obesity (body mass index ≥30 kg/m2) was independently associated with significantly increased risk of mortality (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 1.36, 95% confidence interval 1.18-1.57, overall P < 0.001). Moreover, obesity was associated with significantly increased risk of infection and driveline infection. The probability to undergo heart transplantation was significantly decreased in obese patients (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 0.59, 95% confidence interval 0.48-0.74, overall P < 0.001). CONCLUSIONS: Obesity at the time of LVAD implantation is associated with significantly higher mortality and increased risk of infection as well as driveline infection. The probability to undergo heart transplantation is significantly decreased. These aspects should be considered when devising a treatment strategy before surgery.

Acute renal failure early after heart transplantation: risk factors and clinical consequences.

Limited information exists about acute renal failure (ARF) early after heart transplantation (HTx). We correlated pre-, per-, and post-operative patient and donor parameters to the risk of developing ARF. We also analyzed the consequences of ARF on kidney function after HTx, risk of later need for chronic dialysis or kidney transplantation, and mortality. In a retrospective study from 1983 to 2007, 145 (25%) of 585 HTx recipients developed ARF, defined as ≥ 26.4 micromol/L or ≥ 50% increase in serum creatinine from pre-operatively to the seventh day post-HTx and/or the need of early post-operative dialysis. Independent risk factors for ARF were intravenous cyclosporine immediately post-operatively (odds ratio [OR] 2.16, 95% CI 1.34-3.50, p = 0.02), donor age (OR 1.02, 95% CI 1.00-1.04, p = 0.02), and pre-operative cardiac output (OR 1.38, 95% CI 1.12-1.71, p = 0.003). The development of ARF was a predictor for short-term survival (≤ 3 months) ranging from 98% for patients who improved their creatinine after HTx vs. 79% for those in need of dialysis (p < 0.001). However, ARF did not predict subsequent end stage renal disease in need of dialysis or renal transplantation. ARF is a common complication post-HTx. As ARF is associated with short-term survival, post-operative strategies of preserving renal function have the potential of reducing mortality. Of avoidable risk factors, the use of intravenous CsA should be discouraged.

Long-term continuous flow mechanical biventricular support: 9 years and counting.

We report 2 continuous flow HeartWareTM left ventricular assist devices successfully used in a patient with advanced heart failure of giant cell myocarditis origin in a biventricular configuration. Despite technical challenges of adapting a left ventricular assist device engineered for systemic pressure to function as a right ventricular assist device, the addition of dynamic banding on the right ventricular assist device outflow graft allowed successful adaptation of afterload. This patient has now been on biventricular configuration support for 9 years, and remains stable to this day.

Long-Term Survival of Patients With Advanced Heart Failure Receiving an Left Ventricular Assist Device Intended as a Bridge to Transplantation: The Registry to Evaluate the HeartWare Left Ventricular Assist System.

BACKGROUND: The paucity of available hearts for transplantation means that more patients remain on durable left ventricular support for longer periods of time. The Registry to Evaluate the HeartWare Left Ventricular Assist System was an investigator-initiated multicenter, prospective, single-arm database established to collect post-Conformité Européene mark clinical information on patients receiving the HeartWare ventricular assist device system as a bridge to transplantation. This registry represents the longest multicenter follow-up of primary left ventricular assist device outcomes. METHODS: Data were collected on 254 commercial implants performed between February 2009 and March 2012 from 9 centers in Europe (7) and Australia (2). Patients were followed to device explant, heart transplantation, or death. The outcomes of patients through July/August 2018 were analyzed. Summary statistics were used to describe patient demographics, adverse events, length of support, and outcomes for this extended-term cohort. RESULTS: A total of 122 patients were on support for >2 years, and 34 patients were on support for >5 years. Twenty nine patients are still alive on support (support ranging from 1213 to 3396 days), and 23 of those are on their original HeartWare ventricular assist device system. Kaplan-Meier survival through 7 years was 51%. Through 6 years, freedom from any stroke was 82%, while freedom from severely disabling stroke was 89%. CONCLUSIONS: Low rates of heart transplant now require longer periods of left ventricular assist device support in patients. This analysis demonstrates that long-term support using a HeartWare ventricular assist device system offers survival of 51% through 7 years.

Detection of Thromboembolic Events and Pump Thrombosis in HeartWare HVAD Using Accelerometer in a Porcine Model.

We have recently demonstrated that accelerometer-based pump thrombosis and thromboembolic events detection is feasible in vitro. This article focuses on detection of these conditions in vivo. In an open-chest porcine model (n = 7), an accelerometer was attached to the pump casing of an implanted HeartWare HVAD. Pump vibration was analyzed by Fast Fourier Transform of the accelerometer signals, and the spectrogram third harmonic amplitude quantified and compared with pump power. Interventions included injection of thrombi into the left atrium (sized 0.3-0.4 ml, total n = 35) and control interventions; pump speed change, graft obstruction, and saline bolus injections (total n = 47). Graft flow to cardiac output ratio was used to estimate the expected number of thrombi passing through the pump. Sensitivity/specificity was assessed by receiver operating characteristic curve. Graft flow to cardiac output ratio averaged 66%. Twenty-six of 35 (74%) thrombi caused notable accelerometer signal change. Accelerometer third harmonic amplitude was significantly increased in thromboembolic interventions compared with control interventions, 64.5 (interquartile range [IQR]: 18.8-107.1) and 5.45 (IQR: 4.2-6.6), respectively (p < 0.01). The corresponding difference in pump power was 3 W (IQR: 2.9-3.3) and 2.8 W (IQR: 2.4-2.9), respectively (p < 0.01). Sensitivity/specificity of the accelerometer and pump power to detect thromboembolic events was 0.74/1.00 (area under the curve [AUC]: 0.956) and 0.40/1.00 (AUC: 0.759), respectively. Persistent high third harmonic amplitude was evident at end of all experiments, and pump thrombosis was confirmed by visual inspection. The findings demonstrate that accelerometer-based detection of thromboembolic events and pump thrombosis is feasible in vivo and that the method is superior to detection based on pump power.

International experience using a durable, centrifugal-flow ventricular assist device for biventricular support.

BACKGROUND: Heart transplantation is limited by the scarcity of suitable donors. Patients with advanced biventricular failure may require biventricular support to provide optimal cardiac output and end-organ perfusion. We highlight the outcomes of using the HeartWare HVAD System (HVAD) in a biventricular configuration. METHODS: This retrospective study included patients implanted with HVAD as a biventricular assist device (BiVAD) between 2009 and 2017 at 12 participating centers. When used as a right ventricular assist device (VAD) (RVAD), the HVAD can be attached to the right ventricle (RV) or the right atrium (RA). Kaplan-Meier survival estimates were calculated comparing the 2 RVAD implant locations. Comparisons were also made between the timing of RVAD implantation (primary vs staged) on adverse event (AE) profiles and survival. RESULTS: Among the 93 patients who were implanted with a HVAD BiVAD, Kaplan-Meier survivals at 1-year and 2-year were 56% and 47%, respectively. Survival was independent of the location of the HVAD RVAD implant or whether there was an interval between left VAD and RVAD implantation. The most common AEs were bleeding (35.5%), infection (25.8%), and respiratory failure (20.4%). CONCLUSIONS: This study illustrated similar survival in patients receiving a primary or staged HVAD BiVAD implant at 1 year and 2 years. This study also established that the locations of the RVAD implant (RV or RA) result in similar AE profiles.

In vitro evaluation of PHISIO-coated sets for pediatric cardiac surgery.

OBJECTIVES: Phosphorylcholine coated cardiopulmonary bypass (CPB) circuits for children have been available for some years, but conflicting results regarding the inflammatory response have been reported. Accordingly, we aimed to investigate the effect of phosphorylcholine coating on the inflammatory response. DESIGN: Ten coated and nine uncoated pediatric CPB sets were tested in an in vitro CPB circuit model. The inflammatory response was assessed by serial assays of hemoglobin, hematocrit, leukocyte counts, platelet counts, activation of the complement system, activation of platelets measured as beta-thromboglobulin, activation of neutrophils measured as myeloperoxidase, activation of coagulation measured as prothrombin fragments 1+2, assessment of hemolysis measured as lactate dehydrogenase, and a panel of seven cytokines. Samples were obtained at baseline and after 15, 30, 60 and 120 minutes. RESULTS: There were no significant differences between the phosphorylcholine coated circuits and the uncoated circuits for any of the parameters during the observation period, although a potentially beneficial effect on platelets could not be ruled out. CONCLUSIONS: Phosphorylcholine coating of CPB equipment did not exert any beneficial effect on the inflammatory markers monitored.

Validation of a Holographic Display for Quantification of Mitral Annular Dynamics by Three-Dimensional Echocardiography.

BACKGROUND: Three-dimensional (3D) echocardiography with multiplanar reconstruction (MPR) is used clinically to quantify the mitral annulus. MPR images are, however, presented on a two-dimensional screen, calling into question their accuracy. An alternative to MPR is an autostereoscopic holographic display that enables in-depth visualization of 3D echocardiographic data without the need for special glasses. The aim of this study was to validate an autostereoscopic display using sonomicrometry as a gold standard. METHODS: In 11 anesthetized open-chest pigs, sonomicrometric crystals were placed along the mitral annulus and near the left ventricular apex. High-fidelity catheters measured left atrial and ventricular pressures. Adjustments of pre- and afterload were done by constriction of the inferior vena cava and the ascending aorta, respectively. Three-dimensional epicardial echocardiography was obtained from an apical view and converted to the autostereoscopic display. A 3D virtual semitransparent annular surface (VSAS) was generated to measure commissure width (CW), septal-lateral length, area of the mitral annular surface, nonplanarity angle, and the annular height-to-commissure width ratio in mid-systole and late diastole. RESULTS: Mitral annular measurements from the 3D VSAS derived from the 3D echocardiographic images and autostereoscopic display correlated well with sonomicrometry over a range of loading conditions: CW length (r = 0.98, P < .00001), septal-lateral length (r = 0.98, P < .00001), annular surface area (r = 0.93, P < .001), nonplanarity angle (r = 0.87, P < .001), and annular height-to-commissure width ratio (r = 0.85, P < .01). The 3D VSAS showed better agreement with the sonomicrometric measurements compared with MPR. CONCLUSIONS: Mitral annular measurements using 3D VSAS correlate well with sonomicrometry over a range of loading conditions and may represent a powerful tool for noninvasive quantification of mitral annular dynamics.

Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure.

BACKGROUND: Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses. AIMS: We sought to investigate a potential pathogenic role of LIGHT in chronic HF. METHODS: We used various clinical and experimental approaches including studies in post-infarction HF rats and in vitro studies of endothelial cells and peripheral blood mononuclear cells (PBMC). RESULTS: Our main findings were: (i) LIGHT and its receptors (i.e., HVEM and lymphotoxin-beta receptor) were regulated during experimental HF, with strong expression in the infarcted area accompanied by up-regulation of HVEM in cardiomyocytes and endothelial cells also in the non-ischaemic part of the left ventricle. (ii) Patients with chronic HF had significantly increased expression of LIGHT on CD3(+) T-cells accompanied by increased expression of HVEM on monocytes and within the failing myocardium. (iii) LIGHT induced interleukin (IL)-6 expression in endothelial cells. In HF patients, but not in healthy controls, such an IL-6-inducing effect was also seen in LIGHT activated PBMC. CONCLUSION: Our findings in both clinical and experimental HF may suggest a role for LIGHT signalling pathways in the progression of chronic HF involving IL-6-related mechanisms.

Urgent lung allocation system in the Scandiatransplant countries.

BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.