Multiomic analyses uncover immunological signatures in acute and chronic coronary syndromes.

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS (n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort (n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies.

Heparin dosing in patients with Impella-supported cardiogenic shock.

BACKGROUND: Impella™ is increasingly used in cardiogenic shock. However, thromboembolic and bleeding events are frequent during percutaneous mechanical circulatory support (pMCS). OBJECTIVE: Therefore, we aimed to explore the optimal anticoagulation regime for pMCS to prevent thromboembolism and bleedings. METHODS: This hypothesis-generating multi-center cohort study investigated 170 patients with left-Impella™ support. We (A) compared bleeding/thrombotic events in two centers with therapeutic range (TR-aPTT) activated partial thromboplastin time (60-80s) and (B) compared events of these centers with one center with intermediate range aPTT (40-60s). RESULTS: After matching, there were no differences in patients' characteristics. In centers aiming at TR-aPTT, major bleeding was numerically lower with aPTT <60s within 48 h of left-Impella™ support, versus patients that achieved the aimed aPTT of ≥60s [aPTT ≥60s: 22 (37.3%) vs. aPTT<60s 14 (23.7%); Hazard ratio [HR], 0.62 (95%) CI, 0.28-1.38; p = 0.234]. Major cardiovascular and cerebrovascular adverse events (MACCE) did not differ between groups. In comparison of centers, TR-aPTT strategy showed higher major bleeding rates [TR: 8 (47.1%) vs. intermediate range: 1 (5.9%); HR, 0.06 (95%) CI, 0.01-0.45; p = 0.006]. MACCE were lower in the intermediate range aPTT group as well [TR 12 (70.6%) vs. intermediate range 5 (29.4%) HR, 0.32 (95%) CI, 0.11-0.92; p = 0.034]. CONCLUSION: This pilot analysis showed that lowering UFH-targets in left-Impella™ supported CS patients seems to be a safe and promising strategy for reducing major bleedings without increasing MACCE. This needs to be validated in larger, randomized clinical trials.

Jak2 V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk.

ABSTRACT: JAK2 V617F (JAK2VF) clonal hematopoiesis (CH) has been associated with atherothrombotic cardiovascular disease (CVD). We assessed the impact of Jak2VF CH on arterial thrombosis and explored the underlying mechanisms. A meta-analysis of 3 large cohort studies confirmed the association of JAK2VF with CVD and with platelet counts and adjusted mean platelet volume (MPV). In mice, 20% or 1.5% Jak2VF CH accelerated arterial thrombosis and increased platelet activation. Megakaryocytes in Jak2VF CH showed elevated proplatelet formation and release, increasing prothrombogenic reticulated platelet counts. Gp1ba-Cre-mediated expression of Jak2VF in platelets (VFGp1ba) increased platelet counts to a similar level as in 20% Jak2VF CH mice while having no effect on leukocyte counts. Like Jak2VF CH mice, VFGp1ba mice showed enhanced platelet activation and accelerated arterial thrombosis. In Jak2VF CH, both Jak2VF and wild-type (WT) platelets showed increased activation, suggesting cross talk between mutant and WT platelets. Jak2VF platelets showed twofold to threefold upregulation of COX-1 and COX-2, particularly in young platelets, with elevated cPLA2 activation and thromboxane A2 production. Compared with controls, conditioned media from activated Jak2VF platelets induced greater activation of WT platelets that was reversed by a thromboxane receptor antagonist. Low-dose aspirin ameliorated carotid artery thrombosis in VFGp1ba and Jak2VF CH mice but not in WT control mice. This study shows accelerated arterial thrombosis and platelet activation in Jak2VF CH with a major role of increased reticulated Jak2VF platelets, which mediate thromboxane cross talk with WT platelets and suggests a potential beneficial effect of aspirin in JAK2VF CH.

Comparison of balanced and unbalanced crystalloids as resuscitation fluid in patients treated for cardiogenic shock.

BACKGROUND: The efficacy and safety of saline versus balanced crystalloid solutions in ICU-patients remains complicated by exceptionally heterogenous study population in past comparative studies. This study sought to compare saline and balanced crystalloids for fluid resuscitation in patients with cardiogenic shock with or without out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively analyzed 1032 propensity score matched patients with cardiogenic shock from the Munich University Hospital from 2010 to 2022. In 2018, default resuscitation fluid was changed from 0.9% saline to balanced crystalloids. The primary endpoint was defined as 30-day mortality rate. RESULTS: Patients in the saline group (n = 516) had a similar 30-day mortality rate as patients treated with balanced crystalloids (n = 516) (43.1% vs. 43.0%, p = 0.833), but a higher incidence of new onset renal replacement therapy (30.2% vs 22.7%, p = 0.007) and significantly higher doses of catecholamines. However, OHCA-patients with a lactate level higher than 7.4 mmol/L had a significantly lower 30-day mortality rate when treated with saline (58.6% vs. 79.3%, p = 0.013). In addition, use of balanced crystalloids was independently associated with a higher mortality in the multivariate cox regression analysis after OHCA (hazard ratio 1.43, confidence interval: 1.05-1.96, p = 0.024). CONCLUSIONS: In patients with cardiogenic shock, use of balanced crystalloids was associated with a similar all-cause mortality at 30 days but a lower rate of new onset of renal replacement therapy. In the subgroup of patients after OHCA with severe shock, use of balanced crystalloids was associated with a higher mortality than saline. TRIAL REGISTRATION: LMUshock registry (WHO International Clinical Trials Registry Platform Number DRKS00015860).

Immobility-associated thromboprotection is conserved across mammalian species from bear to human.

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

Suture-based vs. pure plug-based vascular closure devices for VA-ECMO decannulation-A retrospective observational study.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a valuable treatment option for patients in cardiogenic shock, but complications during decannulation may worsen the overall outcome. Therefore, the aim of this study was to compare the efficacy and safety of suture-based to pure plug-based vascular closure devices for VA-ECMO decannulation. Methods: In this retrospective study, the procedural outcome of 33 patients with suture-based Perclose ProGlide closure devices was compared to 38 patients with MANTA plug-based closure devices. Results: Rate of technically correct placement of closure devices was 88% in the suture-based group and 97% in the plug-based group (p = 0.27). There was a significant reduction of severe bleeding events during VA-ECMO decannulation in plug-based versus suture-based systems (3% vs. 21%, p = 0.04). Ischemic complications occurred in 6% with suture-based and 5% with plug-based device (p = 1.00). Pseudoaneurysm formation was detected in 3% in both groups (p = 1.00). No switch to vascular surgery due to bleeding after decannulation was necessary in both groups. Conclusion: Based on our retrospective analysis, we propose that plug-based vascular closure should be the preferred option for VA-ECMO decannulation. This hypothesis should be further tested in a randomized trial.

Heparin-Induced Thrombocytopenia in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation.

Background: Heparin-induced thrombocytopenia (HIT) is a serious, immune-mediated adverse drug reaction to unfractionated heparin (UFH) affecting also patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Although the association between VA-ECMO support and the development of thrombocytopenia has long been known and discussed, HIT as one underlying cause is still insufficiently understood. Therefore, the purpose of this study was to further investigate the epidemiology, mortality, diagnosis, and clinical management of HIT occurring in VA-ECMO patients treated with UFH. Methods: We conducted a retrospective single-center study including adult patients (≥18 years) with VA-ECMO support in the cardiac intensive care unit (ICU) of the University Hospital of Munich (LMU) between January 2013 and May 2022, excluding patients with a known history of HIT upon admission. Differences in baseline characteristics and clinical outcome between excluded HIT (positive anti-platelet factor 4 (PF4)/heparin antibody test but negative functional assay) and confirmed HIT (positive anti-PF4/heparin antibody test and positive functional assay) VA-ECMO patients as well as diagnosis and clinical management of HIT were analysed. Results: Among the 373 patients included, anti-PF4/heparin antibodies were detected in 53/373 (14.2%) patients. Functional HIT testing confirmed HIT in 13 cases (3.5%) and excluded HIT in 40 cases (10.7%), corresponding to a prevalence of confirmed HIT of 13/373 (3.5%) [1.6, 5.3] and a positive predictive value (PPV) of 24.5% for the antibody screening test. The platelet course including platelet recovery following argatroban initiation was similar between all groups. One-month mortality in patients with excluded HIT was 14/40 (35%) and 3-month mortality 17/40 (43%), compared to 5/13 (38%) (p > 0.999), and 6/13 (46%) (p > 0.999) in patients with confirmed HIT. Neurological outcome in both groups measured by the cerebral performance category of survivors on hospital discharge was similar, as well as adverse events during VA-ECMO therapy. Conclusions: With a prevalence of 3.5%, HIT is a non-frequent complication in patients on VA-ECMO and was not associated with a higher mortality rate. HIT was ultimately excluded by functional essay in 75% of VA-ECMO patients with clinical suspicion of HIT and positive anti-PF4/heparin antibody test. Argatroban seems to be an appropriate and safe therapeutic option for confirmed HIT-positive patients on VA-ECMO support.

High On-Treatment Platelet Reactivity: Aspirin versus Clopidogrel.

BACKGROUND: Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in combination with OAC is recommended after PCI for 6-12 months. Clopidogrel is used most frequently in this setting. However, data comparing P2Y12 inhibition with clopidogrel versus cyclooxygenase inhibition by acetylsalicylic acid (ASA, aspirin) is missing. It is well known that the antiplatelet effects of ASA and clopidogrel are frequently impaired (high on-treatment platelet reactivity [HTPR]). In this pilot investigation, we compared the antiplatelet effects of clopidogrel versus ASA. METHODS: In this retrospective single-center database analysis, we investigated platelet reactivity by light transmission aggregometry in patients under different antiplatelet regimes. Results were presented as maximum of aggregation (MoA). HTPR to ASA and to clopidogrel were assessed. RESULTS: 755 patients were enrolled. 677 were on ASA, 521 were on clopidogrel, and 198 had OAC. Overall mean age was 73 ± 13.4 years, and 458 (60.7%) were male. HTPR to ASA occurred in 94/677 patients (13.9%), and mean arachidonic acid-induced MoA was 14.15 ± 19.04%. HTPR to clopidogrel occurred in 241/521 patients (46.3%), and mean adenosine diphosphate-induced MoA was 50.06 ± 20.42%. HTPR to clopidogrel was significantly more frequent than HTPR to ASA; single antiplatelet therapy (SAPT)-mono ASA: 27/199 (13.6%) versus mono clopidogrel: 6/18 (33.3%); p = 0.037; SAPT with OAC-OAC with ASA: 8/35 (22.9%) versus OAC with clopidogrel: 27/60 (45%); p = 0.046. Same difference in HTPR contingency could be shown in subgroups of dual antiplatelet therapy and ASA + clopidogrel + OAC therapy. CONCLUSION: Impaired pharmacodynamic response to clopidogrel was more frequent as HTPR to ASA. Hence, ASA should be tested in combination with OAC post-PCI.

Venting during venoarterial extracorporeal membrane oxygenation.

Cardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics-possibly with concomitant pulmonary congestion and even lung failure-and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.

Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.

Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.

Targeted Temperature Management in Postresuscitation Care After Incorporating Results of the TTM2 Trial.

Cardiac arrest still accounts for a substantial proportion of cardiovascular related deaths and is associated with a tremendous risk of neurological injury and, among the few survivors, poor quality of life. Critical determinants of survival and long-term functional status after cardiac arrest are timely initiation of cardiopulmonary resuscitation and use of an external defibrillator for patients with a shockable rhythm. Outcomes are still far from satisfactory, despite ongoing efforts to improve cardiac arrest response systems, as well as elaborate postresuscitation algorithms. Targeted temperature management at the wide range between 32 °C and 36 °C has been one of the main therapeutic strategies to improve neurological outcome in postresuscitation care. This recommendation has been mainly based on 2 small randomized trials that were published 20 years ago. Most recent data derived from the TTM2 (Targeted Hypothermia Versus Targeted Normothermia After Out-of-Hospital Cardiac Arrest) trial, which included 1861 patients, challenge this strategy. It showed no benefit of targeted hypothermia at 33 °C over normothermia at 36 °C to 37.5 °C with fever prevention. Because temperature management at lower temperatures also correlated with an increased risk of side effects without any benefit in the TTM2 trial, a modification of the guidelines with harmonizing temperature management to normothermia might be necessary.

Staphylococcus aureus increases platelet reactivity in patients with infective endocarditis.

Thromboembolism is frequent in infective endocarditis (IE). However, the optimal antithrombotic regimen in IE is unknown. Staphylococcus aureus (SA) is the leading cause of IE. First studies emphasize increased platelet reactivity by SA. In this pilot study, we hypothesized that platelet reactivity is increased in patients with SA- IE, which could be abrogated by antiplatelet medication. We conducted a prospective, observatory, single-center cohort study in 114 patients with IE, with four cohorts: (1) SA coagulase positive IE without aspirin (ASA) medication, (2) coagulase negative IE without ASA, (3) SA coagulase positive IE with ASA, (4) coagulase negative IE with ASA. Platelet function was measured by Multiplate electrode aggregometry, blood clotting by ROTEM thromboelastometry. Bleeding events were assessed according to TIMI classification. In ASA-naïve patients, aggregation with ADP was increased with coag. pos. IE (coagulase negative: 39.47 ± 4.13 AUC vs. coagulase positive: 59.46 ± 8.19 AUC, p = 0.0219). This was abrogated with ASA medication (coagulase negative: 42.4 ± 4.67 AUC vs. coagulase positive: 45.11 ± 6.063 AUC p = 0.7824). Aspirin did not increase bleeding in SA positive patients. However, in SA negative patients with aspirin, red blood cell transfusions were enhanced. SA coagulase positive IE is associated with increased platelet reactivity. This could be abrogated by aspirin without increased bleeding risk. The results of this pilot study suggest that ASA might be beneficial in SA coagulase positive IE. This needs to be confirmed in clinical trials.

Fibrotic plaques in heart transplanted patients and their association with insulin resistance syndrome and Lp(a).

BACKGROUND: Angiographic evidence of cardiac allograft vasculopathy (CAVangio) is a major limiting factor to survival after heart transplantation (HTx). Prevention of CAVangio is therefore most relevant. Whether modifiable risk factors could be targeted for the prevention of fibrotic plaques, that are common and related to CAVangio, is not clear. METHODS AND RESULTS: In a cohort of 74 consecutive HTx patients (median post-transplant interval 9.2 [4.1-15.5] years), we used the high resolution of optical coherence tomography (OCT) to quantify angulation parameters (maximal and mean arc) and plaque load (mean arc*relative plaque length) of fibrotic plaques. Mean arc was defined as the mean value of all angulation measurements per patient. We assessed the association between cardiovascular risk factors and OCT findings. Linear regression analysis showed a significant association of TG/HDL-c with mean fibrotic arc (12.7 [3.9-21.5], p = 0.006) and fibrotic plaque load (2298 [617-3979], p = 0.009) after adjustment for recipient age and sex. We used the median value of fibrotic plaque load to define high fibrotic plaque load. In binary logistic regression analysis, TG/HDL-c (odds ratio [OR] 1.81 with 95% CI [1.09-3.03], p = 0.02) and Lp(a) (OR 1.02 [1.00-1.05], p = 0.02) were associated with high fibrotic plaque load. Multivariable logistic regression analysis confirmed Lp(a) as significant predictor of high fibrotic plaque load (OR 1.03 [1.01-1.05], p = 0.02). CONCLUSION: TG/HDL-c ratio, a surrogate of insulin resistance syndrome, and Lp(a) were significantly associated with fibrotic plaque in HTx patients. Insulin resistance syndrome and Lp(a) might therefore represent additional targets for CAV prevention.

Incidence and Outcome of Patients with Cardiogenic Shock and Detection of Herpes Simplex Virus in the Lower Respiratory Tract.

(1) Herpes simplex virus (HSV) reactivation in critically ill patients can cause infection in the lower respiratory tract, prolonging mechanical ventilation. However, the association of HSV reactivation with cardiogenic shock (CS) is unclear. As CS is often accompanied by pulmonary congestion and reduced immune system activity, the aim of our study was to determine the incidence and outcome of HSV reactivation in these patients. (2) In this retrospective, single-center study, bronchial lavage (BL) was performed on 181 out of 837 CS patients with mechanical ventilation. (3) In 44 of those patients, HSV was detected with a median time interval of 11 days since intubation. The occurrence of HSV was associated with an increase in C-reactive protein and the fraction of inspired oxygen at the time of HSV detection. Arterial hypertension, bilirubin on ICU admission, the duration of mechanical ventilation and out-of-hospital cardiac arrest were associated with HSV reactivation. (4) HSV reactivation could be detected in 24.3% of patients with CS on whom BL was performed, and its occurrence should be considered in patients with prolonged mechanical ventilation. Due to the limited current evidence, the initiation of treatment for these patients remains an individual choice. Dedicated randomized studies are necessary to investigate the efficacy of antiviral therapy.

Propofol versus midazolam sedation in patients with cardiogenic shock - an observational propensity-matched study.

PURPOSE: Benzodiazepines are recommended as first line sedative agent in ventilated cardiogenic shock patients, although data regarding the optimal sedation strategy are sparse. The aim of this study was to investigate the hemodynamic effects of propofol versus midazolam sedation in our cardiogenic shock registry. MATERIALS AND METHODS: Mechanically ventilated patients suffering from cardiogenic shock were retrospectively enrolled from the cardiogenic shock registry of the university hospital of Munich. 174 patients treated predominantly with propofol were matched by propensity-score to 174 patients treated predominantly with midazolam. RESULTS: Catecholamine doses were similar on admission but significantly lower in the propofol group on days 1-4 of ICU stay. Mortality rate was 38% in the propofol and 52% in the midazolam group after 30 days (p = 0.002). Rate of ≥BARC3 bleeding was significantly lower in the propofol group compared to the midazolam group (p = 0.008). Sedation with midazolam was significantly associated with ICU mortality. CONCLUSION: In this observational cohort study, sedation with propofol in comparison to midazolam was linked to a reduced dose of catecholamines, decreased mortality and bleeding rates for patients with cardiogenic shock. Based on this study and in contrast to current recommendations, propofol should be given consideration for sedation in cardiogenic shock patients.

Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on a range of novel platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently, a novel complication of SARS-CoV-2-targeted adenovirus vaccines has emerged: immune thrombocytopenia, either isolated, or accompanied by thrombosis (then termed VITT). This complication is characterized by low platelet counts, and in the case of VITT, also by platelet-activating platelet factor 4 antibodies reminiscent of heparin-induced thrombocytopenia, leading to a prothrombotic state with clot formation at unusual anatomic sites. Here, we detected antiplatelet antibodies targeting platelet glycoprotein receptors in 30% of patients with proven VITT (n = 27) and 42% of patients with isolated thrombocytopenia after ChAdOx1 nCov-19 vaccination (n = 26), indicating broad antiplatelet autoimmunity in these clinical entities. We use in vitro and in vivo models to characterize possible mechanisms of these platelet-targeted autoimmune responses leading to thrombocytopenia. We show that IV but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation in mice. After IV injection, these aggregates are phagocytosed by macrophages in the spleen, and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet-associated complications after ChAdOx1 nCov-19 administration and highlights accidental IV injection as a potential mechanism of platelet-targeted autoimmunity. Hence, preventing IV injection when administering adenovirus-based vaccines could be a potential measure against platelet-associated pathologies after vaccination.

Assessment of sex- and age-dependency of risk factors for intimal hyperplasia in heart transplant patients using the high resolution of optical coherence tomography.

BACKGROUND: Intimal hyperplasia in cardiac allograft vasculopathy (CAVIH) is limiting survival in pediatric and adult patients after heart transplantation (HTx). Analysis of risk factors for CAVIH using the high resolution of intracoronary optical coherence tomography (OCT) is scarce, particularly in children, and recommendations for CAV prevention are largely based on data obtained in adults. Whether the predictive value of risk factors is age- or sex-dependent is unknown. METHODS AND RESULTS: We used OCT to test the age- and sex-dependency of established risk factors regarding pathological CAVIH in a cohort of 102 pediatric and adult HTx patients (35% <18 years, 69% male). Modifiable parameters such as lipid values, and the diagnoses of dyslipidemia and diabetes showed age- and sex-dependent differences. Regarding CAVIH, receiver-operating characteristic analysis showed that LDL-c was relevant only in female patients (area under the curve [AUC] 0.79, p = 0.007), and total cholesterol in female (AUC 0.81; p = 0.004) and pediatric patients (AUC 0.73, p < 0.05). The association of dyslipidemia with CAVIH was stronger in adult (odds ratio [OR] 6.33) than in pediatric patients (OR 5.00) and in women (OR 6.00) than in men (OR 4.57). Diabetes was associated with CAVIH only in women (OR 11.25). CONCLUSION: In our cohort, modifiable risk factors, particularly total cholesterol and dyslipidemia, had a different impact depending on age and sex. Targeting risk factors in selected patients might improve individual CAVIH prevention.

Percutaneous Transvalvular Microaxial Flow Pump Support in Cardiology.

The Impella device (Impella, Abiomed, Danvers, MA) is a percutaneous transvalvular microaxial flow pump that is currently used for (1) cardiogenic shock, (2) left ventricular unloading (combination of venoarterial extracorporeal membrane oxygenation and Impella concept), (3) high-risk percutaneous coronary interventions, (4) ablation of ventricular tachycardia, and (5) treatment of right ventricular failure. Impella-assisted forward blood flow increased mean arterial pressure and cardiac output, peripheral tissue perfusion, and coronary blood flow in observational studies and some randomized trials. However, because of the need for large-bore femoral access (14 F for the commonly used Impella CP device) and anticoagulation, the incidences of bleeding and ischemic complications are as much as 44% and 18%, respectively. Hemolysis is reported in as many as 32% of patients and stroke in as many as 13%. Despite the rapidly growing use of the Impella device, there are still insufficient data on its effect on outcome and complications on the basis of large, adequately powered randomized controlled trials. The only 2 small and also underpowered randomized controlled trials in cardiogenic shock comparing Impella versus intra-aortic balloon pump did not show improved mortality. Several larger randomized controlled trials are currently recruiting patients or are in preparation in cardiogenic shock (DanGer Shock [Danish-German Cardiogenic Shock Trial; NCT01633502]), left ventricular unloading (DTU-STEMI [Door-To-Unload in ST-Segment-Elevation Myocardial Infarction; NCT03947619], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO], and REVERSE [A Prospective Randomised Trial of Early LV Venting Using Impella CP for Recovery in Patients With Cardiogenic Shock Managed With VA ECMO; NCT03431467]) and high-risk percutaneous coronary intervention (PROTECT IV [Impella-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function; NCT04763200]).

Manual Compression versus Suture-Mediated Closure Device Technique for VA-ECMO Decannulation.

Background: The impact of devices for vessel closure on the safety and efficacy of cannula removal in VA-ECMO patients is unknown. Methods: We retrospectively analyzed 180 consecutive patients weaned from VA-ECMO after cardiac arrest or cardiogenic shock from January 2012 to June 2020. In the first period (historical technique group), from January 2012 to December 2018, primary decannulation strategy was manual compression. In the second period (current technique group), from January 2019 to June 2020, decannulation was performed either by a conventional approach with manual compression or by a suture-mediated closure device technique. Results: A femoral compression system was necessary in 71% of patients in the historical group compared to 39% in the current technique group (p < 0.01). Vascular surgery was performed in 12% in the historical cohort and 2% in the current technique cohort, which indicated a clear trend, albeit it did not reach significance (p = 0.07). Conclusion: We illustrated that a suture-mediated closure device technique for VA-ECMO decannulation was feasible, safe, and may have reduced the need of surgical interventions compared to manual compression alone.