Acute and short-term fluctuations in gravity are associated with changes in circulatory plasma protein levels.

Gravitational changes between micro- and hypergravity cause several adaptations and alterations in the human body. Besides muscular atrophy and immune system impairment, effects on the circulatory system have been described, which can be associated with a wide range of blood biomarker changes. This study examined nine individuals (seven males, two females) during a parabolic flight campaign (PFC). Thirty-one parabolas were performed in one flight day, resulting in ~22 s of microgravity during each parabola. Each participant was subjected to a single flight day with a total of 31 parabolas, totaling 11 min of microgravity during one parabolic flight. Before and after (1 hour (h) and 24 h), the flights blood was sampled to examine potential gravity-induced changes of circulating plasma proteins. Proximity Extension Assay (PEA) offers a proteomic solution, enabling the simultaneous analysis of a wide variety of plasma proteins. From 2925 unique proteins analyzed, 251 (8.58%) proteins demonstrated a differential regulation between baseline, 1 h and 24 h post flight. Pathway analysis indicated that parabolic flights led to altered levels of proteins associated with vesicle organization and apoptosis up to 24 h post microgravity exposure. Varying gravity conditions are associated with poorly understood physiological changes, including stress responses and fluid shifts. We provide a publicly available library of gravity-modulated circulating protein levels illustrating numerous changes in cellular pathways relevant for inter-organ function and communication.

Outcome of Patients Managed by Percutaneous Left Ventricular Assist Device Implantation During On-Hours and Off-Hours.

Percutaneous left ventricular assist devices (pVADs) may be used in patients with cardiogenic shock (CS) to stabilize hemodynamics and maintain sufficient end-organ perfusion. Vascular complications are commonly observed in patients with pVAD support. We aimed to assess the relationship between pVAD implantation time and access-site complication rates. This retrospective observational study included all patients who underwent pVAD insertion for the treatment of CS at our university hospital between 2014 and 2021 (n = 224). Depending on the pVAD insertion time, the patients were assigned to the on-hours (n = 120) or off-hours group (n = 104). Both groups had comparable baseline characteristics and comorbidities. The rate of access-site-related complications was higher in the off-hours group than in the on-hours group (26% vs. 10%, p = 0.002). Premature discontinuation of pVAD support to prevent limb ischemia or manage access-site bleeding was required more often in the off-hours group than in the on-hours group (14% vs. 5%, p = 0.016). Pre-existing peripheral artery disease and implantation time off-hours were independent predictors for access-siterelated vascular complications. In conclusion, patients with CS in whom pVAD was inserted during off-hours had higher rates of access-site-related complications and premature discontinuation of pVAD support than those in whom pVAD was inserted during on-hours.

Evaluation of risk factors for cytomegalovirus DNAemia after end of regular prophylaxis after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid (CMV-DNAemia) within the first weeks after HTx is recommended. METHODS: All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV-DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV-DNAemia (CMV group) and were compared to patients without CMV-DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data. RESULTS: Positive donors and negative recipients (D+/R-) and negative donors and positive recipients (D-/R+) serology was significantly increased and D-/R- decreased in the CMV group (p < .01). Furthermore, the mean age was 57.7 ± 8.7 years but only 53.6 ± 10.0 years for controls (p = .03). Additionally, the intensive care unit (p = .02) and total hospital stay (p = .03) after HTx were approximately 50% longer. Interestingly, the incidence of CMV-DNAemia during prophylaxis was only numerically increased in the CMV group (5.7%, respectively, 0.7%, p = .10), the same effect was also observed for postoperative infections. Multivariate analyses confirmed that D+/R- and D-/R+ CMV immunoglobulin G match were independent risk factors for postprophylaxis CMV-DNAemia. CONCLUSION: Our data should raise awareness of CMV-DNAemia after the termination of regular prophylaxis, as this affects one in five HTx patients. Especially old recipients as well as D+/R- and D-/R+ serology share an elevated risk of late CMV-DNAemia. For these patients, prolongation, or repetition of CMV prophylaxis, including antiviral drugs and CMV immunoglobulins, may be considered.

Comparison of costs associated with transcatheter mitral valve repair: PASCAL vs MitraClip in a real-world setting.

AIMS: We aimed to conduct a clinical process cost analysis to evaluate all upcoming costs of mitral valve transcatheter edge-to-edge repair (M-TEER) treatment using the MitraClip and the PASCAL repair system. METHODS: First, we prospectively enrolled 107 M-TEER patients treated with either the PASCAL or MitraClip system and compared all upcoming costs during the M-TEER procedure and the associated in-hospital stay. Second, we retrospectively analysed 716 M-TEER procedures with regard to the occurrence of complications and their associated costs. All materials used in the catheterization laboratory for the procedures were evaluated. The cost analysis considered various expenses, such as general in-hospital costs, device costs, catheter laboratory and material costs. RESULTS: In the prospective study, 51 patients were treated using the PASCAL system, and 56 were treated using the MitraClip system. The two groups had comparable baseline characteristics and comorbidities. The total in-hospital costs were 25 414 (Interquartile range (IQR) 24 631, 27 697) € in the PASCAL group and 25 633 (IQR 24 752, 28 256) € in the MitraClip group (p = 0.515). The major cost driver was initial material expenditure, mostly triggered by device costs, which were similar to the PASCAL and MitraClip systems. Overall intensive care unit and general ward costs did not differ between the PASCAL and MitraClip groups. In the retrospective analysis, M-TEER-related complications were rare but were associated with higher costs, mainly due to prolonged hospitalisation. CONCLUSION: The major cost driver of M-TEER was the material expenditure, which was mostly triggered by high device costs. The costs of treating patients were similar for the PASCAL and MitraClip systems. M-TEER-related complications are associated with higher costs, mainly due to prolonged hospitalisation. This analysis provides valuable insights into reducing expenses by modifying the process of M-TEER.

Synchronous Donor Heart and Lung Procurement Does Not Impair Outcomes After Heart Transplant.

OBJECTIVES: Donor hearts frequently originate from donors whose lungs are also recovered for transplant. Synchronous heart and lung procurement is more complex than procurement ofthe heart alone, and the effects on outcomes are debated. This study examines the effect of synchronous procurement on outcomes in heart transplant recipients. MATERIALS AND METHODS: This single-center study included patients who received a heart transplant from September 2010 to June 2022. Main outcomes were overall mortality and mortality at 30 days, 3 months, 1 year, and 3 years and morbidity within the first year. We analyzed overall mortality using KaplanMeier survival analysis. Logistic regression was used for the remaining outcomes, adjusting for covariates. P < .05 was considered significant. RESULTS: Our study included 253 heart transplant recipients (72.3% male, mean age 55.0 years), of which 184 patients (72.7%) received hearts from donors of heart and lung, and 69 (27.3%) received hearts from donors of only hearts. Heart-and-lung donors were younger than heart-only donors (43.2 vs 47.2 years; P = .017). Transplant recipient baseline characteristics were not different between the 2 groups. Receipt of hearts from heart-and-lung donors was not associated with higher overall mortality (P = .33) or mortality at 3 months (P = .199), 1 year (P = .348), or 3 years (P = .375), and even showed better 30-day survival than receipt of hearts from heart-only donors (p=0.035). Recipients of hearts from heart-and-lung donors did not have higher rates of postoperative mechanical circulatory support, resternotomy, or pacemaker implantation within the first year. CONCLUSIONS: Our study confirms that synchronous heart and lung procurement for transplant is not associated with worse outcomes in heart transplant recipients and that hearts originating from heart-andlung donors may even be associated with improved outcomes.

Early Postoperative Neurologic Events Are Associated With Worse Outcome and Fatal Midterm Survival After Adult Heart Transplantation.

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P<0.001), and higher need for blood transfusion, and need for hemodialysis after HTx was substantially higher (81% versus 55%; P=0.01). Resternotomy (36% versus 26%; P=0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P=0.02) were also significantly higher in patients with neurologic events. Covariable-adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30-day (hazard ratio [HR], 2.5 [95% CI, 1.0-6.0]; P=0.049), 1-year (HR, 2.2 [95% CI, 1.1-4.3]; P=0.019), and overall (HR, 2.5 [95% CI, 1.5-4.2]; P<0.001) mortality after HTx and reduced Kaplan-Meier survival up to 5 years after HTx (P<0.001). Conclusions Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Reply to Thet et al. Comment on "Oehler et al. Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit. Life 2022, 12, 1053".

Myat Soe Thet et al. published a letter [...].

The impact of gender and frailty on the outcome of older patients with functional mitral regurgitation.

AIMS: Functional mitral regurgitation (MR) is the second most common valvular heart disease worldwide and is increasing with age. The present study investigates the gender distribution and 1 year prognosis of older patients (≥65 years) with pharmacologically treated MR in a real-world population with moderate to severe functional MR. METHODS AND RESULTS: This a single-centre retrospective observational cohort study and included 243 medically treated patients with moderate to severe MR from 2014 to 2020. Echocardiography was performed at baseline. The combined endpoint was hospitalization due to heart failure and all-cause death. There were more female than male patients (42% vs. 58%) without differences regarding age (81 ± 7 years in males vs. 82 ± 8 years in females, P = 0.24). Heart failure symptoms were distributed equally in both groups. Almost half of the patients evidenced a high EuroSCORE II (41%/42%). Atrial fibrillation was frequent, affecting 65% male and 64% female patients (P = 0.89). There were no differences regarding medical treatment. In both genders, two-thirds of the patients displayed MR grade II° (71% (72), and 69% (97)), and one-third showed MR grade III° (29% (30) vs. 31% (44), respectively, P = 0.76). Although males had larger left ventricular end-diastolic diameter, lower ejection fraction (39% (16) vs. 48% (14), P < 0.001), and more dilated left atria. After 1 year, genders did not differ regarding the combined primary endpoint of hospitalization due to heart failure and all-cause mortality (32% (33) for males vs. 29% (41) for females, P = 0.61). One-year mortality was low and equal in both cohorts (11% in males and 9% in females, P = 0.69). In univariate Cox regression proportion hazard model, being female was not associated with the primary endpoint (hazard ratio 0.87 (95% confidence interval 0.55 to 1.37), P = 0.54). Multivariable adjustment for EuroSCORE II and frailty did not result in a significant change regarding the impact of the female gender. CONCLUSIONS: Despite better left ventricular systolic function, mortality in medically treated older female patients suffering from functional mitral regurgitation is not lower than in males. In this real-world cohort, frailty was a stronger predictor of clinical outcome than gender.

Lactate to Albumin Ratio for Predicting Clinical Outcomes after In-Hospital Cardiac Arrest.

In-hospital cardiac arrest (IHCA) is associated with high mortality and poor neurological outcomes. Our objective was to assess whether the lactate-to-albumin ratio (LAR) can predict the outcomes in patients after IHCA. We retrospectively screened 75,987 hospitalised patients at a university hospital between 2015 and 2019. The primary endpoint was survival at 30-days. Neurological outcomes were assessed at 30 days using the cerebral performance category scale. 244 patients with IHCA and return of spontaneous circulation (ROSC) were included in this study and divided into quartiles of LAR. Overall, there were no differences in key baseline characteristics or rates of pre-existing comorbidities among the LAR quartiles. Patients with higher LAR had poorer survival after IHCA compared to patients with lower LAR: Q1, 70.4% of the patients; Q2, 50.8% of the patients; Q3, 26.2% of the patients; Q4, 6.6% of the patients (p = 0.001). Across increasing quartiles, the probability of a favourable neurological outcome in patients with ROSC after IHCA decreased: Q1: 49.2% of the patients; Q2: 32.8% of the patients; Q3: 14.7% of the patients; Q4: 3.2% of the patients (p = 0.001). The AUCs for predicting 30-days survival using the LAR were higher as compared to using a single measurement of lactate or albumin. The prognostic performance of LAR was superior to that of a single measurement of lactate or albumin for predicting survival after IHCA.

Impact of circadian rhythm and daytime variation on outcome after heart transplantation.

INTRO: Recently, the impact of circadian rhythm and daytime variation on surgical outcomes has attracted interest. Although studies for coronary artery and aortic valve surgery report contrary results, effects on heart transplantation have not been studied. METHODS: Between 2010 and February 2022, 235 patients underwent HTx in our department. The recipients were reviewed and categorized according to the start of the HTx procedure - between 04:00 am and 11:59 am (morning, n = 79), 12:00 pm and 07:59 pm (afternoon, n = 68) or 08:00 pm and 03:59 am (night, n = 88). RESULTS: The incidence of high urgency status was slightly but not significantly increased (p = .08) in the morning (55.7%), compared to the afternoon (41.2%) or night (39.8%). The most important donor and recipient characteristics were comparable among the three groups. The incidence of severe primary graft dysfunction (PGD) requiring extracorporeal life support (morning: 36.7%, afternoon: 27.3%, night: 23.0%, p = .15) was also similarly distributed. In addition, there were no significant differences for kidney failure, infections, and acute graft rejection. However, the incidence of bleeding that required rethoracotomy showed an increased trend in the afternoon (morning: 29.1%, afternoon: 40.9%, night: 23.0%, p = .06). 30-day survival (morning: 88.6%, afternoon: 90.8%, night: 92.0%, p = .82) and 1-year survival (morning: 77.5%, afternoon: 76.0%, night: 84.4%, p = .41) were comparable between all groups. CONCLUSION: Circadian rhythm and daytime variation did not affect the outcome after HTx. Postoperative adverse events as well as survival were comparable throughout day- and night-time. As the timing of the HTx procedure is rarely possible and depends on the timing of organ recovery, these results are encouraging, as they allow for the continuation of the prevalent practice.

Donor Noradrenaline Support Is Not Associated with Decreased Survival in Heart Transplant Recipients.

Objective: Although the application of higher doses of norepinephrine (NE) in potential organ donors is a frequent reason for heart decline, its associations with outcomes after heart transplantation (HTx) are discussed controversially. Therefore, we aimed to explore donor NE support's potential impact on outcomes in our single-center heart transplant cohort. Methods: All patients who had undergone HTx in our center between September 2010 and April 2022 (n = 241) were screened for eligibility. From those, all patients with complete data on donor NE support (n = 238) were included. Recipients were divided into three groups according to their donor NE support: without support (n = 26), with low support of 0.01−0.2 µg/kg/min (n = 132), and with high support of > 0.2 µg/kg/min (n = 80). Receiver operating characteristics (ROC) and Kaplan Meier analysis was used to investigate the association of donor NE support and mortality after heart transplantation. Recipient and donor variables, including peri- and postoperative characteristics, were reviewed and compared. Results: NE support in donors ranged between 0 and 2.94 µg/kg/min (median 0.13 µg/kg/min, IQR 0.05−0.26 µg/kg/min). No association between donor NE support and mortality after HTx was observed (AUC for overall survival 0.494). Neither Kaplan-Meier analysis in survival up to 5 years after transplantation (Log Rank p = 0.284) nor group comparisons showed significant differences between the groups. With few exceptions, baseline characteristics in recipients and donors were comparable between the groups. Regarding peri- and postoperative parameters, increasing donor NE support was associated with a longer duration of mechanical ventilation (68 h and 95 h vs. 47 h), longer postoperative IMC/ICU stay (14 vs. 15 vs. 19 days), and a higher need for mechanical life support post-HTx (26% and 39% vs. 12%). Conclusion: In this retrospective analysis, NE support in donors prior to heart transplantation was unrelated to differing survival after heart transplantation. However, higher doses of donor NE were associated with prolonged ventilation, longer duration on IMC/ICU, and a higher need for extracorporeal life support in recipients post-HTx.

Virtual and augmented reality in critical care medicine: the patient's, clinician's, and researcher's perspective.

Virtual reality (VR) and augmented reality (AR) are aspiring, new technologies with increasing use in critical care medicine. While VR fully immerses the user into a virtual three-dimensional space, AR adds overlaid virtual elements into a real-world environment. VR and AR offer great potential to improve critical care medicine for patients, relatives and health care providers. VR may help to ameliorate anxiety, stress, fear, and pain for the patient. It may assist patients in mobilisation and rehabilitation and can improve communication between all those involved in the patient's care. AR can be an effective tool to support continuous education of intensive care medicine providers, and may complement traditional learning methods to acquire key practical competences such as central venous line placement, cardiopulmonary resuscitation, extracorporeal membrane oxygenation device management or endotracheal intubation. Currently, technical, human, and ethical challenges remain. The adaptation and integration of VR/AR modalities into useful clinical applications that can be used routinely on the ICU is challenging. Users may experience unwanted side effects (so-called "cybersickness") during VR/AR sessions, which may limit its applicability. Furthermore, critically ill patients are one of the most vulnerable patient groups and warrant special ethical considerations if new technologies are to be introduced into their daily care. To date, most studies involving AR/VR in critical care medicine provide only a low level of evidence due to their research design. Here we summarise background information, current developments, and key considerations that should be taken into account for future scientific investigations in this field.

Donor hypernatremia is associated with increased mortality after heart transplantation: A retrospective study.

BACKGROUND AND AIMS: Donor hypernatremia has been associated with primary graft dysfunction in heart transplantation (HTx) and is correlated with impaired outcome following liver and renal transplantation. However, controversial data exist regarding the impact of sodium dysregulation on survival. This study aims to investigate the impact of donor sodium levels on early morbidity and short- and midterm survival following HTx. METHODS: Between September 2010 and June 2021, a total of n = 218 patients underwent HTx in our center. From those, 214 could be included retrospectively in our study. For each donor, sodium levels were collected and different cut-off levels from 145 to 159 mmol/L were investigated by Kaplan-Meier-analysis. Then, recipients were divided in three groups regarding donor sodium: Normonatremia (133-145 mmol/L, n = 73), mild hypernatremia (146-156 mmol/L, n = 105) and severe hypernatremia (>156 mmol/L, n = 35). Recipient and donor variables were reviewed and compared, including peri- and postoperative characteristics and recipient survival after up to 5 years after transplantation. RESULTS: All patients were comparable regarding baseline characteristics and perioperative parameters. Regarding early mortality, 90-day survival was significantly reduced only in patients with severe donor hypernatremia in comparison to normonatremia (90% vs. 71%, p = .02), but not in mild hypernatremia (89%, p = .89). One-year survival was comparable in all groups (p > .28). CONCLUSION: Severe donor hypernatremia was associated with reduced short-term survival, while the correlation weakens > 1 year after HTx. As our study is limited due to the nature of its retrospective, single-center approach, future prospective studies are needed to evaluate the importance of donor management with regard to hypernatremia.

Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit.

Prolonged treatment of organ donors in the intensive care unit (ICU) may be associated with complications influencing the outcome after heart transplantation (HTx). We therefore aim to explore the potential impact of the donor length of stay (LOS) in the ICU on outcomes in our cohort. We included all patients undergoing HTx in our center between September 2010 and April 2022 (n = 241). Recipients were divided around the median into three groups regarding their donor LOS in the ICU: 0 to 3 days (≤50th percentile, n = 92), 4 to 7 days (50th-75th percentile, n = 80), and ≥8 days (≥75th percentile, n = 69). Donor LOS in the ICU ranged between 0 and 155 days (median 4, IQR 3-8 days). No association between the LOS in the ICU and survival after HTx was observed (AUC for overall survival 0.514). Neither the Kaplan-Meier survival analysis up to 5 years after HTx (Log-Rank p = 0.789) nor group comparisons showed significant differences. Baseline recipient characteristics were comparable between the groups, while the donor baselines differed in some parameters, such as less cardiopulmonary resuscitation prior to HTx in those with a prolonged LOS. However, regarding the recipients' peri- and postoperative parameters, the groups did not differ in all of the assessed parameters. Thus, in this retrospective analysis, although the donors differed in baseline parameters, the donor LOS in the ICU was not associated with altered recipient survival or outcome after HTx.

[COVID-19 after heart transplantation: experiences from a German transplantation center]. / COVID-19 nach Herztransplantation: Erfahrungen eines deutschen Transplantationszentrums.

Background: The pandemic caused by SARS-CoV­2 (severe acute respiratory syndrome coronavirus type 2) has led to hospitalizations and increased mortality worldwide. With potentially high prevalence and severity of COVID-19 in cardiac transplantation, there is a great need to generate data in this at-risk cohort. Objective: We report here our experience with COVID-19 (coronavirus disease 2019) in heart transplant recipients at a German transplantation center longitudinally over the previous pandemic waves and place it in context to published experiences of other centers. Material and methods: All adult patients who had received a heart transplant at our center and had confirmed COVID-19 infection (n = 12) were included and retrospectively characterized. Results: The mean age was 61.5 (49-63) years, and the majority were male (83%). Comorbidities such as diabetes (42%), arterial hypertension (43%), and chronic renal failure (67%) were found. Passive immunization (convalescent plasma/monoclonal antibodies) was performed in 50%. Oxygen administration was required in 33% of patients; only one patient required noninvasive ventilation (8%), and no patient required invasive ventilation or mechanical cardiovascular support (ECMO). No new cardiovascular or thromboembolic events were found. Conclusion: We could longitudinally not detect severe courses or increased mortality of COVID-19 in heart transplant patients. Prospective studies are needed to make better prognostic estimates of COVID-19 in (heart) transplant patients in the future.

Ischemic Versus Nonischemic Recipient Indication Does Not Impact Outcome After Heart Transplantation.

OBJECTIVES: Heart transplant is the treatment of choice for patients with end-stage heart failure who remain symptomatic despite optimal medical therapy. The primary indications for heart transplant worldwide have been nonischemic cardiomyopathy and ischemic cardiomyopathy. For the 2 indications, patients differ in underlying pathomechanisms leading to their disease and consecutively in relevant comorbidities. However, the influence of an indication of ischemic or nonischemic cardiomyopathy for heart transplant on recipient outcomes posttransplant remains controversial. Here, we investigated whether ischemic or nonischemic cardiomyopathy indication were associated with patient morbidity and mortality after heart transplant. MATERIALS AND METHODS: We included all patients undergoing heart transplant in our center between September 2010 and June 2021 (n = 218). Recipients were divided into 2 groups related to their indication: ischemic (n = 92; 42%) and nonischemic cardiomyopathy (n = 126; 58%). Recipient and donor variables were reviewed and compared, including peri- and postoperative characteristics and recipient survival up to 5 years posttransplant. RESULTS: Although patients with nonischemic cardiomyopathy were significantly younger (51.7 vs 59.1 years; P < .001), had fewer previous cardiac surgeries (56% vs 75%; P = .01), and less frequent severe infections or sepsis (19% vs 32%; P = .03), other outcome-related parameters such as need for extracorporeal life support posttransplant (26% vs 33%), rejection within index stay (7% vs 8%), and survival after 30 days (88% vs 92%), 90 days (85% vs 88%) or 1 year (76% vs 77%) were different. CONCLUSIONS: In this retrospective analysis, although barring different baseline characteristics, ischemic versus nonischemic recipient diagnosis was not associated with outcome or survival after heart transplant.

Fatal outcome of isolated patients who suffered an in-hospital cardiac arrest.

AIM: Isolation of patients in single-patient rooms for infection control precautions leads to less contact with medical staff. Our objective was to assess whether isolated patients who suffer an in-hospital cardiac arrest (IHCA) have lower survival as non-isolated IHCA patients. METHODS: We screened for IHCA occurrence and the isolation state in 75.987 patients that had been hospitalized from 2016 to 2019 at the university hospital. Primary endpoint was survival to discharge. Neurological outcome was assessed using the cerebral performance category scale. RESULTS: In five consecutive years, 4,249 out of 75,987 patients (5.6%) had to be isolated for infection control precautions. In-hospital cardiac arrest occurred in 32 (0.8%) of these isolated patients and in 410 out of 71,738 non-isolated patients (0.6%) (p = 0.130). Propensity score matching yielded 30 isolated and 30 non-isolated patients who suffered an IHCA, without a difference in baseline characteristics and characteristics of cardiac arrests between the groups. Only one out of 30 isolated patients (3.3%) survived to discharge after IHCA compared to 11 non-isolated patients (36.6%) (risk difference, 33.3% [95% CI, 14.9%-51.7%]. None of the 30 isolated patients were discharged with good neurological outcomes compared to nine out of 30 non-isolated IHCA patients (30%) (risk difference, 30% [95% CI, 13.6%-46.4%]). In the multivariate analysis, patient isolation was an independent predictor of poor survival after IHCA (OR, 18.99; 95% CI, 2.467-133.743). CONCLUSIONS: Isolation of patients for infection control precautions is associated with considerable poorer survival and neurological outcome in case these patients are suffering an IHCA.

IgM-enriched immunoglobulin as adjuvant therapy for heart transplant after infection of left ventricular assist devices.

Patients undergoing heart transplantation (HTx) with active infection of left ventricular assist devices (LVAD) are at high risk for postoperative infections. Between 2021 and 2022, five (P1-P5) of a total of n = 44 patients underwent HTx in our department while suffering from LVAD infection. Postoperatively, patients received adjuvant IgM-enriched human intravenous immunoglobulin (IGM-IVIG), consisting of 76% IgG, 12% IgM, and 12% IgA as a novel approach to prevent infective complications. While in P1, P2, and P4, LVAD driveline infection was known before HTx; in P3 and P5, abscess of device pocket was found incidentally during HTx. After a single dose of IGM-IVIG, all patients showed adequate rise in serum immunoglobulins. In the postoperative course, no patient developed infective complications. All patients were successfully discharged and in good condition at the last follow-up. Therefore, IGM-IVIG seems to be an effective adjuvant treatment for patients undergoing HTx with LVAD infections.

Full-length transcriptomic analysis in murine and human heart reveals diversity of PGC-1α promoters and isoforms regulated distinctly in myocardial ischemia and obesity.

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction. RESULTS: Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice. CONCLUSIONS: We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.