Multi‐organ dysfunction syndrome in patients undergoing extracorporeal life support

Background Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. Methods Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. Results The median follow-up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30-day survival and 1-year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR = 2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). Conclusion MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi-organ dysfunction

Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment and haemodynamic factors are associated with increased cardiac mRNA expression of angiotensin-converting enzyme 2 in patients with cardiovascular disease

Aims Coronavirus disease 2019 (COVID-19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic. Methods and results We have measured ACE2 mRNA expression using real-time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB vs. 19 patients that were not ACEi/ARB-treated. We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent of potential confounding comorbidities. Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end-stage heart failure that were treated with ACEi/ARB. On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression. Conclusion Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery disease and in patients with end-stage heart failure. Further trials are needed to test whether this association is deleterious for patients with COVID-19, or possibly protective. Nevertheless, haemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression

Abnormal P‐wave terminal force in lead V 1 is a marker for atrial electrical dysfunction but not structural remodelling

Aims There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V1 (PTFV1) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV1 as a marker for functional, electrical, and structural atrial remodelling. Methods and results Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV1 was assessed as the product of negative P-wave amplitude and duration in lead V1 and defined as abnormal if ≥4000 ms*μV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV1. In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV1 (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV1 showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: −7.336, 95% confidence interval −13.577 to −1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV1 (P = 0.047). This increase in patients with an abnormal PTFV1 was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV1 (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV1 to be a marker for electrical but not structural remodelling. Conclusions Abnormal PTFV1 is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV1 may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation

Outcome after veno‐venous extracorporeal membrane oxygenation in elderly compared to younger patients: A 14‐year retrospective observational study

Background The outcome after veno-venous extracorporeal membrane oxygenation in elderly patients is supposed to be unsatisfactory. Our primary aim was to determine the influence of advanced age on short- and long-term outcomes; the secondary aim was to analyze risk factors for impaired outcomes. Methods Between January 2006 and June 2020, 755 patients received V-V ECMO support at our department. Patients were grouped according to age (18–49.9, 50–59.9, 60–69.9, ≥70 years old), and then retrospectively analyzed for short- and long-term outcomes. Risk factors for in-hospital mortality and death during follow-up were assessed using multivariate regression analysis. Results Duration of V-V ECMO support was comparable between all groups median (8–10 days, p = 0.256). Likewise, the weaning rate was comparable in all age groups 68.2%–76.5%; (p = 0.354), but in-hospital mortality was significantly climbing with increasing age (<50 years 30.1%/n = 91 vs. 50–59.9 years 37.1%/n = 73, vs. 60–69.9 years 45.6%/n = 78 vs. ≥70 years 51.8%/n = 44; p < 0.001). Older age groups also showed significantly reduced cerebral performance category scores. The multivariate logistic analysis yielded age, acute and chronic hemodialysis, bilirubin on day 1 of support, malignancy, and primary lung disease as relevant risk factors for in-hospital mortality. Age, coronary artery disease, presence of another primary lung disease, malignancy, and immunosuppression were risk factors for death during follow-up. Conclusion In V-V ECMO patients, advanced age is associated with more comorbidity, impaired short- and long-term outcome, and worse neurological outcome

Outcome after veno‐arterial extracorporeal membrane oxygenation in elderly patients: A 14‐year single‐center experience

Background Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients is controversial because of presumed poor outcome. Our primary aim was to determine the influence of advanced age on short- and long-term outcome; the secondary aim was to analyze risk factors for impaired outcome. Methods Between January 2006 and June 2020, 645 patients underwent VA-ECMO implantation in our department. The patients were categorized into four groups:<50, 50–59.9, 60–69.9 and ≥70 years old. Data were retrospectively analyzed for short- and long-term outcome. Risk factors for in-hospital mortality and mortality during follow-up were assessed using multivariate regression analysis. Results VA-ECMO support duration was comparable in all age groups (median 3 days). Weaning rates were 60.8%/n = 104 (<50 years), 51.4%/n = 90 (50–59.9 years), 58.8%/n = 107 (60–69.9), and 67.5%/n = 79 (≥70, p = 0.048). Hospital mortality was highest in the patients aged 50–59.9 years (68%/n = 119), but not in the elderly patients (60–69.9, ≥70:62.1%/n = 113, 58,1%/n = 68). At discharge, the cerebral performance category scores were superior in the patients <50 years. Multivariate logistic regression analysis revealed chronic kidney failure requiring hemodialysis, duration of cardiopulmonary resuscitation, and elevated blood lactate levels before VA-ECMO, but not age as predictors of in-hospital mortality. Cox's regression disclosed age as relevant risk factor for death during follow-up. The patients' physical ability was comparable in all age groups. Conclusion VA-ECMO support should not be declined in patients only because of advanced age. Mortality and neurological status at hospital discharge and during follow-up were comparable in all age groups

Perforation of myocardial wall and great vessels after cardiovascular interventions—a 5-year analysis

Background: Less invasive procedures have replaced open surgical treatment in many cardiovascular disorders. During these interventions, iatrogenic cardiac perforation may ensue, which is a severe complication and requires immediate diagnostic assessment and treatment. Methods: From March 2011 to April 2016, all patients referred to the Dept. of Cardio-thoracic Surgery with the diagnosis of iatrogenic perforation of myocardial wall or great vessels were included into the retrospective study. Complications during transapical transcutaneous aortic valve replacements (TAVR) procedures and percutaneous coronary intervention (PCI) were excluded from analysis. Symptoms, therapeutic strategy, intraoperative findings, and outcome were evaluated. Results: Forty-four patients suffered from myocardial wall or vessel perforation. Most common site of perforation were right (n=26; 59.1%) and left (n=8; 18.2%) ventricle. Other structures were involved in ten cases (22.7%). Open surgical treatment was required in 27 cases (61.4%). Mortality after left and right ventricular laceration was 75.0% and 11.5%, respectively. Most common cause of death was cardiocirculatory failure (n=5). Conclusions: Iatrogenic perforation of myocardial wall or central vessels during percutaneous interventional procedures is a rare but life-threatening complication. Despite immediate treatment efforts, mortality is high, particularly after left ventricular laceration

Conventional or minimized cardiopulmonary bypass support during coronary artery bypass grafting? – An analysis by means of perfusion and body mass index

The use of minimized cardiopulmonary bypass support to reduce the side effects of extracorporeal circulation is still contradictorily discussed. This study compares perfusion operated by conventional (CCPB) and minimized (MCPB) cardiopulmonary bypass support during coronary artery bypass grafting (CABG). This study includes the data of 5164 patients treated at our department between 2004 and 2014. Tissue perfusion during cardiopulmonary bypass support and cardiac arrest was assessed by means of body mass index, hemodilution, blood pressure with corresponding pump flow and venous oxygen saturation, serum lactate, and serum pH. Hemodilution was more pronounced after CCPB: hemoglobin had dropped to 4.47 +/- 0.142 g/dL after CCPB and to 2.77 +/- 0.148 g/dL after MCPB (P = 0.0022). Despite the higher pump flow in conventional circuits (4.86-4.95 L/min vs. 4.1-4.18 L/min), mean blood pressure was higher during minimized bypass support (53 +/- 10 vs. 56 +/- 13 mm Hg [aortic clamping], 57 +/- 9 vs. 61 +/- 12 mm Hg [34 degrees C], 55 +/- 9 vs.59 +/- 11 mm Hg [aortic clamp removal], P 70% during both conventional and minimized cardiopulmonary bypass support. The increase in serum lactate was more pronounced after CCPB (8.98 +/- 1.28 vs. 3.66 +/- 1.25 mg/dL, P = 0.0079), corresponding to a decrease in serum pH to acidotic levels (7.33 +/- 0.06 vs. 7.35 +/- 0.06, P < 0.0001). These effects were evident in all BMI ranges. Minimized cardiopulmonary bypass support provides efficient perfusion in all BMI ranges and is thus equivalent to conventional circuits

Is there really a benefit of using minimized cardiopulmonary bypass in CABG? A retrospective propensity score-matched study with 5000 cases

The concept of minimized cardiopulmonary bypass targets at reduction of adverse effects triggered by extracorporeal circulation. In this study, benefits of minimized bypass in CABG were evaluated under particular consideration of patient body mass index and surgeon impact. From 2004 to 2014, 5164 patients underwent coronary bypass surgery (CABG). Conventional cardiopulmonary bypass (CCPB) was used in 2376 patients, minimized cardiopulmonary bypass (MCPB) in 2788 cases. Multivariate regression models were used in the entire cohort and in a propensity score-matched subgroup after expert CABG to figure out clinical differences such as mortality, postoperative renal function, and thromboembolic events. Overall mortality was 1.5% (n = 41) in the MCPB group and 3.5% (n = 82) in CCPB patients (p < 0.001). Postoperative renal failure and hemodialysis occurred in 2.6% (n = 72/MCPB) vs. 5.3% (n = 122/CCPB (p < 0.001). Multivariable regression revealed use of CCPB as risk factor for increased mortality (OR 2.01, p = 0.001), renal failure (OR 1.79, p < 0.001), and myocardial infarction (OR 1.98, p < 0.001) comparable to risk factors such as preoperative ventilation (OR 2.26, p = 0.048), diabetes mellitus (OR 1.68, p = 0.001), and cardiogenic shock (OR 3.81, p = 0.002). Body mass index had no effect on the analyzed outcome parameters (OR 0.92, p = 0.002). Propensity score-matching analysis of an expert CABG subgroup revealed CCPB as risk factor for mortality (OR 2.26, p = 0.004) and postoperative hemodialysis (OR 1.74, p = 0.017). Compared to conventional circuits, minimized bypass use in CABG is associated with lower mortality and less postoperative renal failure. A high body mass index is feasible and not a risk factor for MCPB surgery

Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients

Aims!#!Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.!##!Methods and results!#!A total of 50 transplant patients [1-3 years post heart (42), lung (7), or heart-lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average &amp;gt; tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness.!##!Conclusions!#!The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients