Long COVID is a multisystemic condition with heterogeneous clinical presentations lacking diagnostic biomarkers with discriminatory capacity. This study screened circulating microRNAs as candidate biomarkers for long COVID detection by miRNA sequencing, followed by targeted qPCR quantification focusing on miRNA ratios to reduce technical variability. Overall, 206 long COVID patients ( > 12 weeks after acute infection) and 71 uninfected, unvaccinated healthy controls were recruited through our prospective POSTCOV registry. Candidate microRNAs were screened by microRNA sequencing and quantified by targeted quantitative polymerase chain reaction, focusing on microRNA ratios expressed as cycle-threshold differences. In a training cohort, we developed a logistic regression model based on two microRNA ratios with age and sex as covariates. Internal validation was evaluated using cross validation and bootstraping. We then test the model in an independent external validation cohort processed with the same normalization and ratio definition. Here we show both microRNA ratios (hsa-miR-484/hsa-miR-126-3p, hsa-miR-345-5p/hsa-miR-223-3p) are inversely associated with long COVID. Discrimination in the training cohort is moderate (AUC: 0.760), with acceptable calibration (intercept ~0, slope ~1, Brier score 0.131). In external validation, discrimination decreases (AUC: 0.676) and calibration reveals systematic risk overestimation (intercept −1.88, slope 0.77). Nevertheless, both ratios are consistently lower in long COVID compared to controls. Consistent between-group ratio differences support these microRNAs as candidate biomarkers, whereas limited external model performance highlights the challenges of transportability in heterogeneous long COVID cohorts. Target enrichment indicates inflammatory signaling pathways and integration with drug perturbation profiles suggests compounds for future validation and repurposing studies. Han et al. present a study of serum microRNAs as potential biomarkers of long COVID using machine learning in both training and validation cohorts. They find that consistent differences exist between long COVID patients and controls, but that further validation is required in larger populations. Long COVID is a serious condition resulting from SARS-CoV-2 infection. It is associated with persistent symptoms affecting multiple organ systems, yet objective blood-based markers that could support clinical assessment remain limited. This study evaluates whether small molecules measurable in blood, known as microRNAs, differ between individuals with long COVID and non-long COVID controls. We used a stepwise approach: an initial screen to identify candidate microRNAs, confirmation by a method called RT-qPCR, and testing of a microRNA ratio-based prediction model in an independent validation cohort. Several microRNA ratios show consistent differences between long COVID and controls, while the model performance was decreased in external validation, suggesting sensitivity to cohort and/or technical differences. These findings suggest that measuring circulating microRNAs could eventually help with diagnosis, but further validation in larger, well-matched populations is required before clinical implementation.

Cardioprotection induced by repetitive ischemia/reperfusion (I/R) is not confined to the ischemic region but may extend to distant myocardial territories, a phenomenon termed intracardiac remote ischemic preconditioning (icRIPC). The present study aimed to evaluate the delayed effects of icRIPC on infarct size (IS), left ventricular (LV) function (LVF), and myocardial gene and protein expression. icRIPC was induced in 13 pigs by 3 cycles of 10 min ischemia/10 min reperfusion of the left anterior descending coronary artery (LAD) (conditioning) territory, followed 24 h later by reperfused acute myocardial infarction (AMI) of the left circumflex artery (LCx) (infarcted) territory, induced by 90-min percutaneous balloon occlusion of the mid LCx followed by reperfusion (group icRIPC-AMI). Thirteen additional pigs underwent a sham icRIPC procedure followed by reperfused LCx AMI 24 h later and served as controls (group AMI). Five pigs from each group were euthanized at 3 days, and myocardial expression of nine selected genes was quantified by RT-qPCR in the distal LAD and LCx territories. Protein expression of the two significantly upregulated genes was assessed by Western blot. The remaining eight pigs in each group were followed for 1 month. At 3 days after reperfused AMI, superoxide dismutase-2 (SOD2) protein expression was increased in the infarcted LCx territory of the icRIPC-AMI group, whereas inducible nitric oxide synthase (iNOS/NOS2) protein expression was increased in the distal LAD territory. At 1 month, IS was lower in the icRIPC-AMI than in the AMI group (8.4±3.7

Background Subtype is a key prognostic factor for breast cancer. In HER2-positive disease, HER2-directed therapies have improved outcomes, though they can cause cardiac side effects, potentially leading to emergency department (ED) visits. Objectives To assesses reasons for ED presentations in breast cancer patients, highlighting subtype-specific differences in reason for presentation, 3-month mortality (3MM) and the possible association of cardiologic visits with HER2-directed therapy. Methods In this retrospective study, visits by breast cancer patients at an Austrian tertiary care ED were analysed. Subtype frequency rates and subtype-specific 3MM rates were calculated using Chi-Square tests (separately for early and advanced disease). A possible association between HER2-directed therapies and cardiologic ED visits was investigated using a Fisher’s exact test and a multinomial logistic regression controlling for age. Results There was a total of 463 ED visits among 322 patients between August 2016 and December 2019. Subtype distribution was as follows: 42% (n=135) luminal B-like/HER2- negative, 23% (n=74) triple negative, 16% (n=50) luminal B-like/HER2-positive, 10% (n=33) luminal A-like and 9% (n=30) HER2-positive (non-luminal). In patients with advanced BC, subtype was significantly associated with 3MM (p=0.006), with the highest mortality rate observed in TNBC (54%). Active HER2-directed therapy (n=70) was associated with increased cardiologic ED visits (OR = 4.536 [95%CI, 1.850- 11.125]). Conclusions BC subtype influenced the frequency of ED visits and patient survival. HER2-directed therapy was associated with an increased risk for cardiologic ED visits among real-world cancer patients, emphasizing the need for tailored cardio-oncologic care strategies to optimize tolerability and reduce healthcare burdens.

Circular RNAs (circRNAs) are looped RNA molecules with regulatory roles in myocardial infarction and post-infarction cascades. We aimed to (i) confirm the circularity of novel circRNAs (CDR1as, circ-RCAN2, circ-C12orf29) implicated in myocardial infarction, (ii) examine cell-specific regulation patterns under hypoxia, and (iii) assess their effects on cell viability and downstream miRNA targets. Experiments were conducted on porcine cardiac progenitor cells (pCPCs), bone marrow mesenchymal stem cells (pMSCs) and cardiac fibroblasts (pCFs). Circularity was assessed by RNase R treatment, subsequent qPCR, gel electrophoresis and Sanger sequencing. Hypoxia experiments with/without serum deprivation mimicked ischemia. Effects on viability with/without hypoxia (MTT assay) and downstream miRNA targets were assessed via short interfering RNA (siRNA)-mediated knockdown of circ-RCAN2 and circ-C12orf29. Following RNase R treatment, qPCR product electrophoresis demonstrated amplification of singular products for all circRNAs, with backsplice junction amplification confirmed via Sanger sequencing. Serum deprivation and hypoxia resulted in cell-specific circRNA expression patterns, with an upregulation of all candidates in pCPCs across all intervals of hypoxia, an upregulation of circ-RCAN2 and circ-C12orf29 in pMSCs with prolonged hypoxia, and no detectable dysregulation in pCFs. siRNA knockdown of circ-RCAN2 reduced pCF- and increased pMSC-viability. circ-C12orf29 knockdown increased pCPC- and reduced pMSC-viability. circ-C12orf29 knockdown also upregulated ssc-miR-21-5p and ssc-miR-181c in pCPCs, with no detectable targets for circ-RCAN2. In conclusion, CDR1as, circ-RCAN2 and circ-C12orf29 are circular and dysregulated in a time- and cell-type-specific manner following hypoxia. circ-RCAN2 and circ-C12orf29 exhibit cell-type specific effects on viability, with circ-C12orf29 also targeting downstream miRNAs.

Cardiac miR-132 has been proposed as a target for heart failure (HF) therapy. CDR132L, a rationally designed synthetic oligonucleotide inhibitor of miR-132 has proved pre-clinical efficacy in non-ischaemic and ischaemic large animal HF models. The safety and tolerability of CDR132L were tested in chronic HF patients in a Phase 1b study (NCT04045405) and is currently being tested in a Phase 2 trial in post-MI HF patients (NCT05350969). The aim of the current study was to gain further data on myocardial function and efficacy of CDR132L by analysing left ventricular (LV) and atrial (LA) wall motion by serial cardiac magnetic resonance (cMRI) strain imaging in a clinically relevant large animal (pig) model of chronic HF. Animals (15 per group) were randomized 1-month post-MI and received five intravenous (i.v.) monthly treatments with CDR132L (5 mg/kg) or placebo and were followed up for 6-month post-MI. LV and LA strain parameters were deteriorated after MI over time but significantly ameliorated by CDR132L treatment, compared with placebo. Strain parameters showed significant correlations with pharmacodynamic measures such as ejection fraction, NT-proBNP, and cardiac interstitial fibrosis in remodelling hearts 6 months post-MI. LV and LA motion and contractility were improved by repeated monthly dosing of CDR132L in a large animal model of HF with reduced ejection fraction model with first dose given one month post-MI. The results highlight the translational value and usability of MRI-based cardiac strain imaging in HF drug development and support further clinical development of CDR132L.

Sodium-glucose cotransporter 2-Inhibitors (SGLT2i) have demonstrated benefits for patients with heart failure (HF), regardless of their diabetes status and left ventricular ejection fraction (LVEF). Cancer therapy induced cardiac dysfunction (CTRCD) encompasses a broad spectrum of cardiovascular complications resulting from cancer treatments including myocardial ischemia, coronary vasospasm, and arrhythmias. Recent retrospective clinical studies suggest a benefit in cancer patients with diabetes and chemotherapy with concomitanty SGLT-2i therapy (1). Translational studies suggest an anticancer effect e.g. by antiangiogenesis and mitochondrial effects (2). This study aimed to assess the cardiac effectiveness and overall safety of SGLT2 inhibitors in patients undergoing cancer treatment. Prospective cancer patients with different malignancies or survivors of childhood cancer, undergoing cancer treatment with radiotherapy and/or additional chemo- or immune therapy, who received a SGLT2i therapy were evaluated at baseline and at 6 months follow-up. 61 of the 83 patients received chemotherapy with, for example, anthracyclines , alkylating agents and targeted therapy. Transthoracic echocardiography, speckle tracking strain and laboratory assessments were performed in all patients at baseline and follow-up at our cardio-oncology clinic. Here we present preliminary data of the ongoing study. A total of 83 Patients (51% female, 49% male, range 28-85 years) with SGLT2i treatment were analyzed. The most common primary cancer types included cancer of the lungs (23 patients, 28%), breast cancer (23 patients, 28%) followed by the hematologic system (15 patients, 18%), the abdominal system (8 patients, 10%), the skin (7 patients, 8%), cancer in the neck area (3 patients, 4%) and the urogenital system (3 patients, 4%). The median NT-proBNP level at baseline was 490.5 pg/mL (IQR 205-1169). During the treatment with SGLT2i the median NT-proBNP decreased to a level of 436.5 pg/mL (IQR 168-1236) (p=0.021). In echocardiography, reduced systolic left ventricular function was present in 63 patients (76%) and reduced right ventricular function was present in 20 patients (24%). During the study period the mean creatinine stayed stable with an average of 0.8 ± 0.55 mg/dL at baseline and 1.1 ± 0.50 mg/dL at follow-up (p=0.299). The use of SGLT2-Inhibitors is associated with a tendency to improvement in NT-proBNP levels in patients with heart failure undergoing cancer treatment. The treatment with SGLT2-Inhibitors is well tolerated in patients undergoing cancer treatment and no clinically relevant side effects were observed.Cardioprotective Mechanisms of SGLT2i Strain was highly reduced

In cancer survivors, radiotherapy, particularly thoracic radiotherapy, is linked to an increased risk of cardiovascular diseases, including radiotherapy-associated valve disease. Radiotherapy is also associated with an increased risk of coronary heart disease. The co-occurrence of radiotherapy associated valve disease and radiotherapy-associated coronary heart disease is underexplored. Given the growing number of long-term cancer survivors, understanding this relationship is valuable in identifying patients that would benefit from coronary imaging or functional testing when radiotherapy-associated valvular disease is detected on echocardiography. Patients with radiotherapy-associated valvular disease presenting to our cardio-oncology outpatient clinic were included in this study. This includes patients that have a history of thoracic radiotherapy and valve disease consistent with radiotherapy-associated damage. Available thoracic CT imaging data was analyzed for coronary calcifications according to the guidelines on coronary artery calcium scoring of noncontrast noncardiac chest CT-scans [1]. Briefly, each vessel (LM, LAD, LCX, RCA) was visually scored from 0 (none) to 3 (severe) based on the presence of calcifications in <1/3 (1), 1/3-2/3 (=2) or >2/3 (=3) of the vessel. The score was then added up with a maximum score of 12. 44 patients with radiotherapy-associated valvular disease and interpretable CT imaging were included in the study (mean age 65 ± 12.4 years, 61% male, 39% female). The total calcium scores were as follows; none in 27% (n = 12), mild in 23% (n =10), moderate in 9% (n = 4) and severe in 41% (n = 18). Altogether 50% of patients had moderate to severe coronary calcium scores (Table 1). Half of all patients with radiotherapy-associated valvular disease had moderate to severe coronary artery calcifications according to noncontrast, noncardiac chest CT scans. This increased pre-test probability should be considered when evaluating coronary imaging or functional testing in patients in whom radiotherapy-associated valvular disease is detected during routine echocardiography.CAC Severity Table CAC Severity Graph

Background/Objective: The measurement of troponin is recommended for acute myocardial infarction (AMI) diagnosis. Yet, hs-cardiac troponin T (hs-cTnT) can be elevated due to non-cardiac conditions, such as skeletal muscle injury, chronic kidney disease (CKD) or pulmonary embolism. The aim of our study was to compare the diagnostic accuracy of a bedside rapid hs-cardiac troponin I (hs-cTnI) assay (Quidel TriageTrue®) with hs-cTnT measured in a routine laboratory (Roche Elecsys). Methods: This prospective monocentric study was conducted in an acute cardiac outpatient unit at a tertiary hospital. Hs-cTnI was measured via a point-of-care test from whole blood, while hs-cTnT was measured from plasma through the routine laboratory facility. Results: In 129 patients (65.1% male, 61.8 ± 15.6 years) with acute chest pain, results for hs-cTnI were available 14 ± 11 min after the first clinical presentation, which was 74 ± 54 min earlier than for hs-cTnT. Coronary angiography confirmed AMI in 17 patients (13.28%). The relative risk of AMI patients with elevated hs-cTnI results was 6.59 compared to 2.29 for hs-cTnT. Hs-cTnI exhibited an equivalent negative predictive value to hs-cTnT (99%) for AMI but had a comparatively higher positive predictive value (50.0 vs. 25.8%). In 39 patients with at least CKD stage 3a, median hs-cTnT was pathological (27.0 ng/L), in contrast with hs-cTnI (11.2 ng/L). Further, hs-cTnI was less likely elevated in patients with CKD and no AMI. Conclusions: The diagnostic value of hs-cTnI was comparable to that of hs-cTnT, and the blood sampling-to-result time was shorter than routine hs-cTnT.

Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item “Problems in performing usual activities”.

Carcinoid heart disease (CHD) caused by neuroendocrine tumors (NET) is associated with increased morbidity and mortality due to valvular dysfunction and right-sided heart failure. This study aims to assess the prevalence and one-year incidence of CHD in NET patients. Tumor characteristics, laboratory measurements, and echocardiographic findings were examined to identify predictors of CHD development. The study was an investigator-initiated, monocentric, prospective trial. Patients with gastroenterological NET without previously diagnosed CHD were included and underwent oncological and cardiological diagnostics. Transthoracic echocardiography (TTE) and blood test were performed at baseline. Thirty-nine NET patients (mean age 67 ± 11 years) were enrolled into the study and received TTE. A total of four patients exhibited signs of CHD (mean age 69 ± 8.8 years). Four patients showed classical right sided carcinoid heart disease with high-grade tricuspid regurgitation. Two of these patients also exhibited mild to moderate right ventricular dysfunction. One NET patient exhibited aortic stenosis and another had a history of an Ebstein Anomaly. In such cases, the differentiation between preexisting or concomitant valvular disease and its interaction with NET and carcinoid heart disease is difficult. NT-proBNP was significantly elevated in CHD patients compared to NET patients without CHD (810.25 pg/mL ± 651.7 vs. 175.15 pg/mL ± 149.3, p = 0.02) as was 5-Hydroxyindoleacetic acid (5-HIAA) in 24h urine (67 mg ± 26 vs. 11 mg ± 8, p < 0.01) and Troponin T (21 ng/L ± 5 vs. 10.6 ng/L ± 4, p < 0.01). Chromogranin A showed no significant difference (889.25 ng/mL ± 1040.93 vs. 584.54 ng/mL ± 1066.76, p = 0.64) between groups. 10.26% (n = 4) of NET patients showed signs of CHD, all of which showed right-sided carcinoid heart disease. CHD patients exhibited significantly elevated cardiac biomarkers such as proBNP and Troponin T, as well as increased 5-HIAA in 24h urine. The comparatively mild severity of CHD in our patient collective might be due to improvements in the pharmacological treatment of NETs. One CHD patient underwent TriClip implantation with a good result, highlighting the possibility of interventional treatment in these patients.TTE and TEE in CHD Boxplots CHD

Immune checkpoint inhibitors (ICI) have significantly improved outcomes for several malignancies. Despite these benefits, patients with cancer face an increased risk for the development of cardiovascular disease due to mutual risk factors, similar biological mechanisms, as well as cardiotoxic side effects of therapy. Therefore, there is a pressing need for effective risk stratification strategies. This study aimed to explore the association between NT-proBNP levels and the risk of acute cardiovascular hospitalizations and death in patients who receive ICI. We used electronic health records of patients treated with ICI who had available baseline NT-proBNP levels at our Hospital, a tertiary academic center, between January 2017 and July 2022. The primary outcome of interest was the composite of acute cardiovascular hospitalization or death. The associations between NT-proBNP and outcomes were analyzed using cox regression models adjusted for age, sex, serum creatinine, diabetes, HF, CAD, hypertension, AF, LDL-C, and CRP. In total, 550 patients (35% female, median age 65 yrs) were included in the study. The median NT-proBNP levels were 272 pg/mL (IQR 102-742 pg/mL) and 388 (71%) patients had NT-proBNP levels ≥125 pg/mL. During a median FU of 67 weeks, 190 patients (35%) died, and 103 CV hospitalizations occurred in 76 patients (14%). Compared with patients with NT-proBNP concentrations <125, those with NT-proBNP concentrations ≥125 pg/ml had significantly higher event rates of the combined endpoint (12-Month KM event rates: 38% vs 21%, P<0.001). After multivariable adjustment, NT-proBNP remained independently associated with an increased risk of cardiovascular hospitalization and death (Adjusted HR for 1-SD increase in log-transformed biomarker 1.64, 95% CI 1.24 to 2.14; Figure). These data highlight NT-proBNP levels as a valuable marker for identifying patients at increased risk of cardiovascular complications during ICI therapy.Figure

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Cardio-oncology, a burgeoning subspecialty, addresses the complex interplay between cardiology and oncology, particularly in light of increased cardiovascular (CV) disease mortality in cancer patients. This review provides a comprehensive overview of cardio-oncology with a focus on the therapies used in hematological malignancies. We explore the bidirectional relationship between heart failure and cancer, emphasizing the need for collaborative care. The review discusses risk stratification, highlighting the importance of baseline CV risk assessment and personalized surveillance regimens. Primary and secondary prevention strategies, including pharmacological interventions, are outlined. The review also delves into the cardiotoxicity associated with hematological cancer therapies, focusing on anthracyclines, Bruton kinase inhibitors, BCR-ABL tyrosine kinase inhibitors, CAR-T cell therapy, immune checkpoint inhibitors, multiple myeloma treatments, and hematopoietic stem cell transplantation. We then highlight the high risk of venous and arterial thromboembolisms in cancer patients and the challenges of anticoagulation management in cardio-oncology. Finally, the review touches on the importance of long-term follow-up and appropriate screening in cancer survivors at high risk of CV morbidity and mortality, based on their CV risk profile and the type and dose of cardiotoxic therapies they received such as anthracyclines or high radiation doses.

Combined [18F]FDG PET-cardiac MRI imaging (PET/CMR) is a useful tool to assess myocardial viability and cardiac function in patients with acute myocardial infarction (AMI). Here, we evaluated the prognostic value of PET/CMR in a porcine closed-chest reperfused AMI (rAMI) model. Late gadolinium enhancement by PET/CMR imaging displayed tracer uptake defect at the infarction site by 3 days after the rAMI in the majority of the animals (group Match, n = 28). Increased [18F]FDG uptake at the infarcted area (metabolism/contractility mismatch) with reduced tracer uptake in the remote viable myocardium (group Mismatch, n = 12) 3 days after rAMI was observed in the animals with larger infarct size and worse left ventricular ejection fraction (LVEF) (34 ± 8.7 vs 42.0 ± 5.2

Abstract Background Along with the aging population, the incidence of concomitant heart failure with preserved ejection fraction (HFpEF) and cancer, is increasing. However, little is known about the typical characteristics of patients with both HFpEF and a history of oncologic disease. Aim We aimed to characterize the distinctive characteristics and outcomes of patients with a history of cancer within a prospective HFpEF registry. Methods We analyzed data from 491 unselected HFpEF patients from our tertiary university center between 2010 and 2022 and followed the patients until 2023. Laboratory parameters and comorbidities were assessed. Patients were categorized into those with and without a history of cancer, including various malignancies, survivors of childhood cancer, radiation therapy, with or without chemotherapy. Kaplan-Meier estimates were used to explore the association between cancer history, as well as previous radiotherapy, and a combined endpoint of heart failure hospitalization and/or all-cause death. Results In this analysis of 491 HFpEF patients, a total of 101 patients (21%); had a history of cancer [mean age 74±7 years; female 72 (72%), male 29 (29%)]. The median time from cancer diagnosis to the initial HFpEF visit was 7.0 years (IQR 13-0.5 years). The most prevalent primary cancer sites included the chest wall (32%) comprising 4 adenocarcinomas of the lung and 28 cases of breast cancer, followed by the gastric (28%), urogenital system (18%), hematologic and lymphatic system (16%), cancers located at the head and neck (5%) and endocrine malignancies (1%). Radiotherapy (39%) and chemotherapy (26%) were common. Notably, no significant differences were observed, between patients with or without a history of cancer, in terms of median NT-proBNP levels [1037 (IQR 416-2075) vs. 1060 pg/ml (IQR 462-2013)] and the frequency of key cardiovascular comorbidities (all p>0.05, see Table 1). Over the study period [median follow-up 50 months (IQR 18-76)], 64 (64%) of cancer patients met the combined endpoint, with no statistically significant difference in outcomes between HFpEF patients with and without a cancer history (log-rank p=0.222, see Figure 1). Furthermore, there was no significant difference in the combined endpoint between patients who had undergone radiotherapy and those without (log-rank p=0.162). Conclusion Our findings highlight a high coexistence of cancer and HFpEF, which can frequently occur after oncology therapies. The data suggest that the presence of a history of cancer or previous radiotherapy did not significantly impact overall outcomes in HFpEF patients compared to those without cancer during the study period. Further research is needed to characterize patients with both disease entities in detail. Due to modern cardiovascular therapy in a university and cardio-oncology clinic setting, outcomes for cancer patients appear better than expected.

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-DΔNΔC(AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina.MethodsReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated.ConclusionsThe phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present a new case and systematically summarize the available literature. PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. Eighty-one papers were identified, describing 86 cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12 months. Patients mainly complained of dyspnea and chest pain, 60.8

PURPOSE:Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present a new case and systematically summarize the available literature. MATERIALS AND METHODS:PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. RESULTS:Eighty-one papers were identified, describing 86 cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12 months. Patients mainly complained of dyspnea and chest pain, 60.8% had pathologic ECG (electrocardiographic) findings. The cardiac mass was most frequently detected by transthoracic echography. The most common tumor histology was squamous cell carcinoma. Chemotherapy and surgical interventions were the main treatment modalities. Median survival after diagnosis of cardiac metastasis was 3 months. CONCLUSION:This largest review on cardiac metastases from cervical cancer confirmed the heart as a very infrequent site of metastasis. There are < 100 cases described in the literature, with very poor prognosis and undefined clinical management.

Abstract Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms. Here we evaluated reactivation of parvovirus B19 and several viruses of the herpes family in patients with long-COVID syndrome, how vaccination affected viral interference, and how virus reactivation influenced clinical conditions. Clinical and laboratory data on 252 consecutive patients (97 vaccinated and 155 non-vaccinated) were recorded between April 2021–May 2022 (median 243 days post-COVID-19 infection). Viral IgG and IgM titers were compared between vaccinated or non-vaccinated patients, and age and sex-matched healthy controls. Vaccination was associated with significantly less frequent fatigue and multiorgan symptoms (P < 0.001), significantly less cumulative IgM positivity of the investigated viruses, significantly lower plasma levels of IgG subfractions 2 and 4, and significantly lower quantitative Cytomegalovirus (CMV) IgG, CMV IgM, and EBV IgM titers. These results indicate that anti-SARS-CoV2 vaccination interrupts viral crosstalk in patients with long-COVID syndrome. (ClinicalTrials.gov Identifier: NCT05398952)

Abstract Background Heart rate variability (HRV) correlates with the severity and mortality of heart failure. Respiratory sinus arrhythmia (RSA) is defined by the dynamic increase and decrease in heart rate between breaths. Restoration of RSA might be beneficial in patients with heart failure and/or patients in need of permanent pacing. Purpose The aim of this translational, proof-of-principle study was to investigate the effect of pacing with or without RSA using a newly designed pacing device on the left ventricular contractility and cardiac output. Methods The project was initiated with the aim of designing a new pacing device capable of restoring RSA in paced hearts with the help of lung inflation sensors. Neuronal networks were designed to reconstruct the human brain using ultra-low energy-consuming technology. The lung inflation sensor fed the detected inspiration data back to the pacing device, which paced the heart via pacing leads (DDD) in the right atrium and ventricle. In total, 5 intubated but spontaneously breathing landrace pigs were paced without RSA (fixed-rate pacing) and with restored RSA. Stroke volume and cardiac output were measured by echocardiography (diameter of left ventricular outflow tract and velocity time integral measured by pulsed wave doppler averaged over three heart beats). Preload-independent cardiac contractility was measured via a pressure-volume loop catheter in the left ventricle during occlusion of the inferior vena cava. Fig. 1 indicates the setup of the trial. The trials were conducted according to the relevant rules (NIH Publication no. 85-23 revised 1985) and in accordance with national law. Results Echocardiography (n=5) showed a mean left ventricular outflow tract diameter of 21 ± 0.1 mm. The mean intrinsic heart rate was 87 ± 14 bpm, and the mean paced heart rate was 104 ± 5 bpm in the pigs (65 ± 3 kg). The main outcomes are displayed in Fig. 2: The left ventricular stroke volume increased by 11ml (+21%, p=0.036) with 100% RSA compared to pacing without RSA, while cardiac output increased by 1.14 l/min (+21%, p=0.037). The pressure volume area is proportional to the total myocardial oxygen consumption and decreased by 6234 mmHg*ml (-39%, p=0.004). Cardiac efficiency represents the relative amount of blood being pumped consuming one unit energy and increased by 0.163 (+72%, p=0.033). End-systolic pressure volume relationship demonstrated a non-significant increase by 0.183 mmHg/ml (+45%, p=0.25). Parameters of diastolic function (Tau) did not differ between the groups. Conclusion Restoration of RSA by our newly developed pacing device significantly improved the cardiac contractility/output in our proof-of-principle large animal translational model. Chronic trials will be required to definitively confirm the positive effects of RSA on cardiac remodeling.Fig. 1: Set-up of the animal trials.Fig. 2: Main results (mean/std error)