Search

Abstract We describe a case of a 20‐year‐old healthy man developing chest pain and classical symptoms of vaccine reactogenicity 12 h after receiving the first dose of mRNA‐1273 (Moderna). Cardiac troponin T was increased, and subepicardial inflammation and focal contractile dysfunction were detected by cardiac magnetic resonance imaging and echocardiography. We confirmed the diagnosis of acute myocarditis by endomyocardial biopsy demonstrating significant infiltration of monocytes and T lymphocytes. Although we detected IgG against nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) indicating prior infection, the patient repeatedly tested negative for SARS‐CoV‐2 and had been asymptomatic for several months. Furthermore, viral genome analysis of endomyocardial biopsy samples was negative for SARS‐CoV‐2 and other potential cardiotropic viruses. These findings and the strong temporal relation between the vaccination and the symptom onset imply a potential side effect of mRNA‐1273.

Abstract Background This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest. Methods We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event. Results Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592–0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320–0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed. Conclusions A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.

Abstract Aims Patients with heart failure (HF) suffer from reduced quality‐of‐life (QoL). We aimed to compare QoL, depression, and anxiety scores among outpatients with preserved (HFpEF) and reduced (HFrEF) ejection fraction and non‐HF controls and its relationship to coordination capacity. Methods and results Fifty‐five participants were recruited prospectively at the University Hospital Jena, Germany (17 HFpEF, 18 HFrEF, and 20 non‐HF controls). All participants underwent echocardiography, cardiopulmonary exercise testing (CPET), 10 m walking test (10‐MWT), isokinetic muscle function and coordination tests, and QoL assessments using the short form of health survey (SF‐36), and hospital anxiety and depression scale (HADS). Furthermore, inflammatory biomarkers such as growth differentiation factor‐15 (GDF‐15) were assessed. Patients with HFpEF showed compared with HFrEF and non‐HF controls reduced QoL [mental component score (MCS): 43.6 ± 7.1 vs. 50.2 ± 10.0 vs. 50.5 ± 5.0, P = 0.03), vitality (VT): 47.5 ± 8.4 vs. 53.6 ± 8.6 vs. 57.1 ± 5.2, P = 0.004), and elevated anxiety (6.5 ± 3.2 vs. 3.3 ± 2.8 vs. 3.8 ± 2. 8, P = 0.02) and depression scores (6.5 [3.5–10.0] vs. 3.0 [1.0–6.5] vs. 2.0 [0.75–3.0], P = 0.01)]. After adjusting to multiple comparisons, anxiety remained higher in HFpEF patients compared with HFrEF (ppost‐hoc = 0.009). HFpEF and HFrEF patients showed reduced coordination capacity compared with non‐HF controls (P

Abstract Aims Allograft rejection following heart transplantation (HTx) is a serious complication even in the era of modern immunosuppressive regimens and causes up to a third of early deaths after HTx. Allograft rejection is mediated by a cascade of immune mechanisms leading to acute cellular rejection (ACR) and/or antibody‐mediated rejection (AMR). The gold standard for monitoring allograft rejection is invasive endomyocardial biopsy that exposes patients to complications. Little is known about the potential of circulating miRNAs as biomarkers to detect cardiac allograft rejection. We here present a systematic analysis of circulating miRNAs as biomarkers and predictors for allograft rejection after HTx using next‐generation small RNA sequencing. Methods and results We used next‐generation small RNA sequencing to investigate circulating miRNAs among HTx recipients (10 healthy controls, 10 heart failure patients, 13 ACR, and 10 AMR). MiRNA profiling was performed at different time points before, during, and after resolution of the rejection episode. We found three miRNAs with significantly increased serum levels in patients with biopsy‐proven cardiac rejection when compared with patients without rejection: hsa‐miR‐139‐5p, hsa‐miR‐151a‐5p, and hsa‐miR‐186‐5p. We identified miRNAs that may serve as potential predictors for the subsequent development of ACR: hsa‐miR‐29c‐3p (ACR) and hsa‐miR‐486‐5p (AMR). Overall, hsa‐miR‐486‐5p was most strongly associated with acute rejection episodes. Conclusions Monitoring cardiac allograft rejection using circulating miRNAs might represent an alternative strategy to invasive endomyocardial biopsy.

Background: Left ventricular assist devices (LVAD) and extracorporeal membrane oxygenation (ECMO) are well established therapies in heart failure (HF) management. Their use is generally associated with a sudden increase in inflammatory mediators, which are often already elevated in patients with HF prior to device implantation. An exaggerated release of proinflammatory cytokines is associated with organ dysfunction and increased mortality. Hemoadsorption has been shown to reduce inflammatory mediators during cardiopulmonary bypass. Objective: To investigate the role of hemoadsorption during the management of acute or chronic heart failure with mechanical circulatory support and its impact on survival. Methods: We systematically searched MEDLINE selecting all studies comparing the use of hemoadsorption during LVAD implantation or veno-arterial (v.a.) ECMO therapy. Records were screened by two different investigators. Reports without a control group and duplicates were excluded. Results: Our search delivered six studies. One was randomized and five were retrospective studies, of which three were risk-adjusted. During LVAD implantation, one study showed no difference in mortality but higher incidence of respiratory insufficiency in the hemoadsorption group (54% vs 30%, p = 0.024) and the other study found higher mortality in the hemoadsorption group (33% vs 0%, p = 0.01). During ECMO therapy, three of four studies including the randomized one found no difference in survival or major adverse cardiac events between the hemoadsorption and the control groups. Only one study found lower mortality in the hemoadsorption group (20% vs 60%. p = 0.02). Conclusions: The results of this literature review suggest that the use of hemoadsorption in patients undergoing LVAD implantation might be associated with higher morbidity and mortality. The majority of studies on the use of hemoadsorption during v.a. ECMO therapy showed no effect on mortality or organ dysfunction, while only one small study showed that hemoadsorption was able to reduce mortality. The results are limited by the retrospective nature and the small sample sizes of the majority of the studies included.

Despite considerable progress in treating cardiac disorders, the prevalence of heart failure (HF) keeps growing, making it a global medical and economic burden. HF is characterized by profound metabolic remodeling, which mostly occurs in the mitochondria. Although it is well established that the failing heart is energy-deficient, the role of mitochondria in the pathophysiology of HF extends beyond the energetic aspects. Changes in substrate oxidation, tricarboxylic acid cycle and the respiratory chain have emerged as key players in regulating myocardial energy homeostasis, Ca2+ handling, oxidative stress and inflammation. This work aims to highlight metabolic alterations in the mitochondria and their far-reaching effects on the pathophysiology of HF. Based on this knowledge, we will also discuss potential metabolic approaches to improve cardiac function.

Abstract Background Colchicine has been used as anti-inflammatory agent in pericardial effusion (PE). We sought to perform a meta-analysis of randomized trials assessing the efficacy and safety of colchicine in patients with pericarditis or postpericardiotomy syndrome (PPS). Methods In the systematic literature search following the PRISMA statement, 10 prospective randomized controlled studies with 1981 patients with an average follow-up duration of 13.6 months were identified. Results Colchicine reduced the recurrence rate of pericarditis in patients with acute and recurrent pericarditis and reduced the incidence of PPS (RR: 0.57, 95% CI: 0.44–0.74). Additionally, the rate of rehospitalizations as well as the symptom duration after 72 h was significantly decreased in pericarditis (RR 0.33; 95% CI 0.18–0.60; and RR 0.43; 95% CI 0.34–0.54; respectively), but not in PPS. Treatment with colchicine was associated with significantly higher adverse event (AE) rates (RR 1.42; 95% CI 1.05–1.92), with gastrointestinal intolerance being the leading AE. The reported number needed to treat (NNT) for the prevention of recurrent pericarditis ranged between 3 and 5. The reported NNT for PPS prevention was 10, and the number needed to harm (NNH) was 12, respectively. Late colchicine administration ≥ 7 days after heart surgery did not reduce postoperative PE. Conclusions Our meta-analysis confirms that colchicine is efficacious and safe for prevention of recurrent pericarditis and PPS, while it reduces rehospitalizations and symptom duration in pericarditis. The clinical use of colchicine for the setting of PPS and postoperative PE after heart surgery should be investigated in further multicenter RCT.

(1) Background: Pulmonary arterial hypertension (PAH) is a serious condition that is associated with many cardiopulmonary diseases. Invasive right heart catheterization (RHC) is currently the only method for the definitive diagnosis and follow-up of PAH. In this study, we sought a non-invasive hemodynamic biomarker for the diagnosis of PAH. (2) Methods: We applied prospectively respiratory and cardiac gated 4D-flow MRI at a 9.4T preclinical scanner on three different groups of Sprague Dawley rats: baseline (n = 11), moderate PAH (n = 8), and severe PAH (n = 8). The pressure gradients as well as the velocity values were analyzed from 4D-flow data and correlated with lung histology. (3) Results: The pressure gradient between the pulmonary artery and vein on the unilateral side as well as the time-averaged mean velocity values of the small pulmonary arteries were capable of distinguishing not only between baseline and severe PAH, but also between the moderate and severe stages of the disease. (4) Conclusions: The current preclinical study suggests the pulmonary arteriovenous pressure gradient and the time-averaged mean velocity as potential biomarkers to diagnose PAH.

Background: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. Materials and Methods: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. Results: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. Conclusion: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Blood urea nitrogen (BUN) was reported to be associated with mortality in heart failure patients. We aimed to evaluate admission BUN concentration in a heterogeneous critically ill patient collective admitted to an intensive care unit (ICU) for prognostic relevance.A total of 4176 medical patients (67±13 years) admitted to a German ICU between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. Association of admission BUN and both intra-hospital and long-term mortality were investigated by Cox regression. An optimal cut-off was calculated by means of the Youden-Index.Patients with higher admission BUN concentration were older, clinically sicker and had more pronounced laboratory signs of multi-organ failure including kidney failure. Admission BUN was associated with adverse long-term mortality (HR 1.013; 95%CI 1.012-1.014; p28 mg/dL to case-controls ≤ 28mg/dL corrected for APACHE2 scores: BUN above 28 mg/dL remained associated with adverse outcome in a paired analysis with the difference being 5.85% (95%CI 1.23-10.47%; p = 0.02).High BUN concentration at admission was robustly associated with adverse outcome in critically ill patients admitted to an ICU, even after correction for co-founders including renal failure. BUN might constitute an independent, easily available and important parameter for risk stratification in the critically ill.

After publication of the original article [1], we were notified that an author’s name is not complete.

Patients with end-stage liver disease in need of liver transplantation increasingly are older with a greater burden of cardiac disease and other co-morbidities, which may increase perioperative risk and adversely affect long-term prognosis. Cirrhosis of any etiology manifests hemodynamically as a state of low systemic vascular resistance, with high peripheral, but low central blood volume, leading to a state of neurohormonal activation and high cardiac output, which may adversely affect cardiac reserve under extreme perioperative stress, aptly termed cirrhosis-associated or cirrhotic cardiomyopathy. Evidence of asymptomatic cirrhotic cardiomyopathy may be found in subtle electrocardiographic and echocardiographic changes, but may progress to severe heart failure under the demands of bleeding and transfusions, vasopressors, rebounding peripheral vascular resistance, withdrawal of cardioprotective beta-blockers and mineralocorticoid antagonists, exacerbated by sepsis or systemic inflammatory response syndrome. This review will add to the current body of literature on cirrhotic cardiomyopathy by focusing on the role of advanced echocardiographic imaging techniques, cardiac biomarkers, and advanced heart failure therapies available to manage patients with cirrhotic cardiomyopathy while waiting for liver transplant and during the perioperative period.