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Fragestellung: Diese Arbeit setzt sich mit der optimalen Gestaltung der Rückkehr zur sportlichen Betätigung nach einer Infektion mit dem Virus SARS-CoV-2 auseinander. Da die meisten Infektionen bei Athlet*innen, die die Zielgruppe dieser Arbeit darstellen, asymptomatisch oder mildsymptomatisch ablaufen, ist der Fokus der Arbeit auf diese Schwere der Erkrankung gesetzt. Es werden Empfehlungen zur optimalen Wahl der sportfreien Zeit und zur Durchführung von kardialem Screening erarbeitet. Bezüglich des kardialen Screenings wird auf die Auswahl geeigneter Methoden und die Frage, welche Indikationen es für kardiales Screening gibt, eingegangen. Methodik: Als Design wurde eine systematische Literaturarbeit gewählt, dazu wurde eine Literaturrecherche durchgeführt. Diese fand vorwiegend in den Datenbanken PUBMED, PEDro und Cochrane Covid-19 Study Register statt. Durch vorab ausgewählte Ein- und Ausschlusskriterien wurden die Studien gefiltert und passende für die Arbeit herangezogen. Ergebnisse: Aus insgesamt 455 Treffern der Literatursuche wurden insgesamt zehn Studien für die Arbeit herangezogen. Fünf dieser Studien sind in Form einer Expert*innenkonsensuserklärung oder einer Leitlinie verfasst, fünf weitere sind Beobachtungsstudien, die zur Überprüfung der in den Erklärungen und Leitlinien verfassten Empfehlungen dienen sollen. Schlussfolgerung: Laut aktueller Empfehlungen, gepaart mit den Ergebnissen der inkludierten Beobachtungsstudien, ist eine sichere Rückkehr zum Sport bei asymptomatischen Athlet*innen drei Tage nach der Diagnosestellung, bei mildsymptomatischen drei Tage nach den letzten Symptomen möglich. Ein kardiales Screening soll bei asymptomatischen oder mildsymptomatischen Athlet*innen in Ausnahmefällen angedacht, aber nicht routinemäßig bei allen durchgeführt werden. Eine kardiale Diagnostik wäre auf jeden Fall bei kardiopulmonalen Symptomen indiziert, weshalb es für Physiotherapeut*innen bei der Rückkehr zum Sport besonders wichtig ist auf ein Auftreten dieser zu achten. Wenn die Indikation für ein kardiales Screening getroffen wurde, soll dieses, laut aktueller Literatur, aus einer Triade, bestehend aus einer Bestimmung des kardialen Troponins im Blut, einer Echokardiografie und EKG-Testungen in Ruhe und Belastung zusammengesetzt sein und bei Auffälligkeiten durch ein KMR erweitert werden. Topic: This paper focuses on the optimal return to sports after infection with the SARS-CoV-2 virus for asymptomatic and mildly symptomatic athletes. Recommendations are developed for the optimal choice of sports-free time and for the performance of cardiac screening. Regarding cardiac screening, the selection of suitable methods and the question of which indications for cardiac screening exist are addressed. Methodology: A systematic literature review was chosen as the design of this study, and a literature search was conducted. For the search the databases PUBMED, PEDro, and Cochrane Covid-19 Study Register were used. The studies were filtered through pre-selected inclusion and exclusion criteria, and only those deemed suitable for the purpose of this paper were used. Results: Out of a total of 455 hits from the literature search, ten studies were used for the paper. Five of these studies are in the form of an expert consensus statement or a guideline, and five are observational studies, which are intended to verify the recommendations made in the statements and guidelines. Conclusion: According to current recommendations, coupled with the results of the included observational studies, a safe return to sports activities is possible three days after diagnosis for asymptomatic athletes, and three days after the last symptoms for mildly symptomatic athletes. Cardiac screening should only be considered in exceptional cases for asymptomatic or mildly symptomatic athletes and should not be routinely performed on all athletes. Cardiac diagnostics are, for example, indicated in case of cardio-pulmonary symptoms, which is why physiotherapists should watch out for their occurrence. Cardiac screening should consist of a triad, including a determination of cardiac troponin, an echocardiogram, and ECG tests at rest and under stress. Additionally, it may be extended by an MRI in case of abnormalities.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being administered on an unprecedented scale. Assessing the risks of side effects is needed to aid clinicians in early detection and treatment. This study examined the risk of inflammatory heart disease, including pericarditis and myocarditis, after SARS-CoV-2 vaccination. Methods Intermountain Healthcare patients with inflammatory heart disease from December 15, 2020 to June 15, 2021, and with or without preceding SARS-CoV-2 vaccinations, were studied. Relative rates of inflammatory heart disease were examined for vaccinated patients compared to unvaccinated patients. Results Of 67 patients identified with inflammatory heart disease, 21 (31.3%) had a SARS-Cov-2 vaccination within the previous 60 days. Overall, 914 611 Intermountain Healthcare patients received a SARS-CoV-2 vaccine, resulting in an inflammatory heart disease rate of 2.30 per 100 000 vaccinated patients. The relative risk of inflammatory heart disease for the vaccinated patients compared to the unvaccinated patients was 2.05 times higher rate within the 30-day window (P = .01) and had a trend toward increase in the 60-day window (relative rate = 1.63; P = .07). All vaccinated patients with inflammatory heart disease were treated successfully with 1 death related to a pre-existing condition. Conclusions Although rare, the rate of inflammatory heart disease was greater in a SARS-CoV-2-vaccinated population than the unvaccinated population. This risk is eclipsed by the risk of contracting coronavirus disease 2019 and its associated, commonly severe outcomes. Nevertheless, clinicians and patients should be informed of this risk to facilitate earlier recognition and treatment.

Background Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS‐C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. Methods and Results We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS‐C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive‐inotropic requirements. Compared with controls, cases with MIS‐C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS‐C had abnormal left ventricular function ( | global longitudinal strain | Conclusions Myocardial function is globally decreased in MIS‐C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin‐6 and interleukin‐8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS‐C.

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disorder associated with premature atherosclerosis and increased cardiovascular risk. Systemic inflammation is an emerging risk factor for coronary microvascular dysfunction (CMD). We aimed to test whether CMD, defined as abnormal myocardial flow reserve (MFR) by positron emission tomography‐computed tomography, would be independently associated with SLE after adjusting for nonobstructive atherosclerotic burden and common cardiovascular risk factors. Methods and Results Consecutive patients with SLE who underwent symptom‐prompted stress cardiac positron emission tomography‐computed tomography were included (n=42). Obstructive coronary artery disease and systolic dysfunction were excluded. MFR was quantified by positron emission tomography‐computed tomography, and CMD was defined as MFR P P =0.017). Conclusions We demonstrated that patients with SLE with cardiac symptoms without obstructive coronary artery disease have a high prevalence of coronary vasomotor abnormalities. In comparison with symptomatic matched controls, patients with SLE have a more severe reduction in MFR that is not accounted for by common cardiovascular factors or atherosclerotic burden.

Background Transcriptomic studies have contributed to fundamental knowledge of myocardial remodeling in human heart failure (HF). However, the key HF genes reported are often inconsistent between studies, and systematic efforts to integrate evidence from multiple patient cohorts are lacking. Here, we aimed to provide a framework for comprehensive comparison and analysis of publicly available data sets resulting in an unbiased consensus transcriptional signature of human end‐stage HF. Methods and Results We curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts. First, we evaluated the degree of consistency between studies by using linear classifiers and overrepresentation analysis. Then, we meta‐analyzed the deregulation of 14 041 genes to extract a consensus signature of HF. Finally, to functionally characterize this signature, we estimated the activities of 343 transcription factors, 14 signaling pathways, and 182 micro RNAs, as well as the enrichment of 5998 biological processes. Machine learning approaches revealed conserved disease patterns across all studies independent of technical differences. These consistent molecular changes were prioritized with a meta‐analysis, functionally characterized and validated on external data. We provide all results in a free public resource ( https://saezlab.shinyapps.io/reheat/ ) and exemplified usage by deciphering fetal gene reprogramming and tracing the potential myocardial origin of the plasma proteome markers in patients with HF. Conclusions Even though technical and sampling variability confound the identification of differentially expressed genes in individual studies, we demonstrated that coordinated molecular responses during end‐stage HF are conserved. The presented resource is crucial to complement findings in independent studies and decipher fundamental changes in failing myocardium.

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2‐dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross‐sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction 3 versus Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.

Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one‐disease continuum has been discussed. Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% (P

Background Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis. Methods and Results We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7–11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3–134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2–28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%–26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes. Conclusions The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.

Background Risk stratification of Chagas disease patients in the limited‐resource setting would be helpful in crafting management strategies. We developed a score to predict 2‐year mortality in patients with Chagas cardiomyopathy from remote endemic areas. Methods and Results This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi‐Trop cohort (The São Paulo‐Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all‐cause mortality. The patients were classified into 3 risk categories at baseline (low

Background Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) share many histopathologic and clinical features. Whether they are parts of a one‐disease continuum has been discussed. Methods and Results We compared medical record data of 351 CS and 28 GCM cases diagnosed in Finland since the late 1980s and followed until February 2018 for a composite end point of cardiac death, aborted sudden death, and heart transplantation. Heart failure was the presenting manifestation in 50% versus 15% ( P P =0.044), of GCM and CS, respectively. At presentation, left ventricular ejection fraction was ≤50% in 81% of cases of GCM versus in 48% of CS ( P =0.004). The median (interquartile range) of plasma NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was 5273 (2782–11309) ng/L on admission in GCM versus 859 (290–1950) ng/L in CS ( P P P Conclusions GCM differs from CS in presenting with more extensive myocardial injury and having worse long‐term outcome. Yet the key determinant of prognosis appears to be the extent of myocardial injury rather than the histopathologic diagnosis.

Background Increasing studies demonstrated that the cardiac involvements are related to coronavirus disease 2019 (COVID‐19). Thus, we investigated the clinical characteristics of patients with COVID‐19 and further determined the risk factors for cardiac involvement in them. Methods and Results We analyzed data from 102 consecutive laboratory‐confirmed and hospitalized patients with COVID‐19 (52 women aged 19–87 years). Epidemiologic and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, chest imaging findings, management methods, and clinical outcomes were collected. Patients were divided into acute cardiac injury, with and without cardiac marker abnormities groups according to different level of cardiac markers. In this research, cardiac involvement was found in 72 of the 102 (70.6%) patients: tachycardia (n=20), electrocardiography abnormalities (n=23), echocardiography abnormalities (n=59), elevated myocardial enzymes (n=55), and acute cardiac injury (n=9). Eight patients with acute cardiac injury were aged >60 years; seven of them had ≥2 underlying comorbidities (hypertension, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and chronic kidney disease). Novel coronavirus pneumonia was much more severe in the patients with acute cardiac injury than in patients with nondefinite acute cardiac injury ( P Conclusions Cardiac involvements are common in patients with COVID‐19. Elevated CRP levels, old age, underlying comorbidities, and novel coronavirus pneumonia severity are the main risk factors for cardiac involvement in patients with COVID‐19. More attention should be given to cardiovascular protection during COVID‐19 treatment for mortality reduction. Registration URL: https://www.chictr.org ; Unique identifier: ChiCTR2000029955.

Background Patients with rheumatoid arthritis are at twice the risk of ventricular arrhythmia and sudden cardiac death as the general population. We hypothesize that β‐blocker treatment of rheumatoid arthritis is antiarrhythmic by producing synergistic anticatecholaminergic and anti‐inflammatory effects. Methods and Results Collagen‐induced arthritis (CIA) was induced in Lewis rats by immunization with type II collagen in Freund's incomplete adjuvant. The treatment with propranolol (4 mg/kg) started on the first day of immunization. We evaluated the ventricular vulnerability to ventricular arrhythmia using in vivo programmed stimulation and performed ex vivo optical mapping to measure the electrical remodeling of the heart. The ventricular tissue was further processed for immunohistochemical staining and protein array analysis. The assessment of ventricular vulnerability showed that the number and duration of the induced ventricular arrhythmia episodes were increased in CIA rats, which were improved with propranolol treatment. The sympathovagal index and the plasma level of catecholamines significantly increased in CIA rats, whereas the use of propranolol attenuated sympathetic hyperactivity. In the optical mapping study, electrical remodeling, characterized by prolonged action potential duration, slow conduction velocity, and steepened action‐potential duration restitution, were noted in CIA rats and reversed in the propranolol‐treatment group. The propranolol treatment was associated with decreases in paw thickness, fewer inflammatory cell infiltrations in the heart, reduced levels of cardiac inflammatory cytokines, and less cardiac fibrosis as compared with the CIA group. Conclusions CIA increased ventricular arrhythmia vulnerability through sympathetic hyperinnervation and proarrhythmic ventricular electrophysiological remodeling. Treatment with propranolol in CIA rats was both anti‐inflammatory and antiarrhythmic.

Background Inflammation may contribute to incident heart failure ( HF ). Rheumatoid arthritis ( RA ), a prototypic inflammatory condition, may serve as a model for understanding inflammation‐related HF risk. Methods and Results Using the Vanderbilt University Medical Center electronic health record, we retrospectively identified 9889 patients with RA and 9889 control patients without autoimmune disease matched for age, sex, and race. Prevalent HF at entry into the electronic health record or preceding RA diagnosis was excluded. Incident HF was ascertained using International Classification of Diseases, Ninth Revision (ICD‐9), codes and medications. Over 177 566 person‐years of follow‐up, patients with RA were at 21% greater risk of HF (95% CI, 3–42%) independent of traditional cardiovascular risk factors. Among patients with RA , higher CRP (C‐reactive protein) was associated with greater HF risk ( P HF risk ( P =0.021). In a second cohort (n=115) of prospectively enrolled patients with and without RA , we performed proteomics and cardiac magnetic resonance imaging to discover circulating markers of inflammation associated with cardiac structure and function. Artemin levels were higher in patients with RA compared with controls ( P =0.009), and higher artemin levels were associated with worse ventricular end‐systolic elastance and ventricular‐vascular coupling ratio ( P =0.044 and P =0.031, respectively). Conclusions RA , a prototypic chronic inflammatory condition, is associated with increased risk of HF . Among patients with RA , higher levels of CRP were associated with greater HF risk, while methotrexate was associated with lower risk.

Inflammatory heart disease (IHD) is a group of diseases that includes pericarditis, myocarditis, and endocarditis. Although males appear to be more commonly affected than females, IHD can be seen in any age group. While the disease can be self-limiting leading to full recovery, affected individuals can develop chronic disease, suggesting that identification of primary triggers is critical for successful therapies. Adding to this complexity, however, is the fact that IHD can be triggered by a variety of infectious and non-infectious causes that can also occur as secondary events to primary insults. In this review, we discuss the immunological insights into the development of IHD as well as a mechanistic understanding of the disease process in animal models.

Background Troponin levels are frequently obtained in pediatric patients, but the benefit remains unclear. Methods and Results This retrospective study included 1993 patients aged 0 to 21 years without history of cardiac disease in whom troponin levels were obtained during clinical evaluation of cardiac and noncardiac presentations. Troponin was elevated (≥0.1 ng/mL) in 182 patients (9%). A cardiac diagnosis was made in 109 (60%) of those with elevated troponin and in 208 (12%) of those without ( P Conclusions Troponin can be a useful adjunctive test in the evaluation of children when the differential diagnosis includes cardiac etiologies. Serial measurement was not helpful when troponin was elevated at presentation but may merit consideration when the initial level is not elevated and there is ongoing concern about cardiac involvement. Lower reference values may be appropriate when evaluating children in contrast to adults.

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy–related cardiac dysfunction ( CTRCD ) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high‐sensitivity cardiac troponin T (hs‐ cTnT ), NT ‐pro BNP (N‐terminal pro‐B‐type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value CTRCD . Early increases in all biomarkers occurred with anthracycline‐based regimens. hs‐ cTnT levels >14 ng/L at anthracycline completion were associated with a 2‐fold increased CTRCD risk (hazard ratio, 2.01; 95% CI , 1.00–4.06). There was a modest association between changes in NT ‐pro BNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI , −1.8 to –0.4] with each NT ‐pro BNP doubling). Increases in NT ‐pro BNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI , 1.32–1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI , 1.04–1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01173341.

Background Coronary artery aneurysms and myocarditis are well‐recognized complications of Kawasaki disease ( KD ) but no systematic evaluation of the consequences of myocarditis has been performed in the subset presenting with low ejection fraction ( EF ). We postulated that more severe myocardial inflammation as evidenced by low EF during the acute phase could lead to late myocardial fibrosis. Methods and Results We measured the carboxyterminal propeptide of procollagen type I ( PIPC ), soluble suppressor of tumorigenicity 2, galectin‐3 (Gal‐3), growth‐differentiation factor‐15, and calprotectin by ELISA in late convalescent blood samples from 16 KD patients who had an EF ≤55% on their initial echocardiogram. Results were compared with samples from sex‐ and age‐matched KD patients with initial EF >60%. In the univariate analysis, the median Gal‐3 and PIPC levels in the low EF group were significantly higher than those in the normal EF group (Gal‐3: low EF 6.216 versus normal EF 4.976 mg/dL P =0.038, PIPC : low EF 427.4 versus normal EF 265.2 mg/dL, P =0.01). In a multivariable analysis, there were significant differences for Gal‐3 and PIPC levels between the low and normal EF groups, adjusting for age, sex, and worst z score. Conclusions Convalescent KD patients with a history of low EF during the acute illness had significantly elevated levels of Gal‐3 and PIPC when compared with matched‐control KD patients with normal EF . These findings raise concern for myocardial fibrosis as a potential late sequela of the more severe myocarditis experienced by a subset of KD patients during the acute phase.

Background The SNRK (sucrose‐nonfermenting–related kinase) enzyme is critical for cardiac function. However, the underlying cause for heart failure observed in Snrk cardiac conditional knockout mouse is unknown. Methods and Results Previously, 6‐month adult mice knocked out for Snrk in cardiomyocytes (CMs) displayed left ventricular dysfunction. Here, 4‐month adult mice, on angiotensin II (Ang II) infusion, show rapid decline in cardiac systolic function, which leads to heart failure and death in 2 weeks. These mice showed increased expression of nuclear factor κ light chain enhancer of activated B cells (NF‐κB), inflammatory signaling proteins, proinflammatory proteins in the heart, and fibrosis. Interestingly, under Ang II infusion, mice knocked out for Snrk in endothelial cells did not show significant systolic or diastolic dysfunction. Although an NF‐κB inflammation signaling pathway was increased in Snrk knockout endothelial cells, this did not lead to fibrosis or mortality. In hearts of adult mice knocked out for Snrk in CMs, we also observed NF‐κB pathway activation in CMs, and an increased presence of Mac2+ macrophages was observed in basal and Ang II–infused states. In vitro analysis of Snrk knockdown HL‐1 CMs revealed similar upregulation of the NF‐κB signaling proteins and proinflammatory proteins that was exacerbated on Ang II treatment. The Ang II–induced NF‐κB pathway–mediated proinflammatory effects were mediated in part through protein kinase B or AKT, wherein AKT inhibition restored the proinflammatory signaling protein levels to baseline in Snrk knockdown HL‐1 CMs. Conclusions During heart failure, SNRK acts as a cardiomyocyte‐specific repressor of cardiac inflammation and fibrosis.

Background Heart failure (HF) is one of the most significant causes of morbidity and mortality for the cardiovascular risk population. We found previously that extracellular HSP70 (heat shock protein) is an important trigger in cardiac hypertrophy and fibrosis, which are associated with the development of heart dysfunction. However, the potential role of HSP70 in response to HF and whether it could be a target for the therapy of HF remain unknown. Methods and Results An HF mouse model was generated by a single IP injection of doxorubicin at a dose of 15 mg/kg. Ten days later, these mice were treated with an HSP70 neutralizing antibody for 5 times. We observed that doxorubicin treatment increased circulating HSP70 and expression of HSP70 in myocardium and promoted its extracellular release in the heart. Blocking extracellular HSP70 activity by its antibody significantly ameliorated doxorubicin‐induced left ventricular dilation and dysfunction, which was accompanied by a significant inhibition of cardiac fibrosis. The cardioprotective effect of the anti‐HSP70 antibody was largely attributed to its ability to promote the resolution of myocardial inflammation, as evidenced by its suppression of the toll‐like receptor 2–associated signaling cascade and modulation of the intracellular distribution of the p50 and p65 subunits of nuclear factor‐κB. Conclusions Extracellular HSP70 serves as a noninfectious inflammatory factor in the development of HF, and blocking extracellular HSP70 activity may provide potential therapeutic benefits for the treatment of HF.

Background: Sarcoidosis is a multisystem granulomatous disease of not sufficiently understood origin. Some patients develop cardiac involvement in course of the disease which is mostly responsible for adverse outcome. In addition to complications like high degree atrioventricular (AV) block or ventricular tachyarrhythmias, there is a certain percentage of patients developing atrial tachyarrhythmias. Data is limited and the role of catheter ablation uncertain. Therefore, we studied sarcoid patients who presented with supraventricular tachyarrhythmias. Hypothesis: Treatment and ablation of supraventricular tachycardia could be hampered by inflammation in patients with cardiac sarcoidosis. Methods: We enrolled 37 consecutive patients with cardiac sarcoidosis who presented with atrial tachyarrhythmias and underwent an electrophysiologic study over a period of 6 years (03/2013-04/2019). In total, 16 catheter ablations for atrial tachyarrhythmias were performed. Mean follow-up duration was 2.5 years. Results: Most common ablation performed was cavo-tricuspid isthmus ablation for typical atrial flutter in seven patients (54%). Pulmonary vein isolation for treatment of atrial fibrillation (AF) was performed in five patients (38%). Two patients received slow-pathway modulation for treatment of recurrent atrioventricular nodal reentry tachycardia (AVNRT). All but two patients with AF had no clinical recurrence during follow-up. Two patients had recurrence of AF but still reported markedly improved european heart rhythm association (EHRA) class. Periprocedural safety was very high. There were no adverse events related to the ablation procedure. One patient died during follow-up in the presence of electrical storm. Conclusion: Catheter ablations of supraventricular tachycardias seem to be safe and effective in patients with cardiac sarcoidosis. Outcome is comparable to patients without inflammatory heart disease, although data from larger patient collectives are mandatory to make recommendations in this special entity., Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.