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BackgroundDuring the early phase of the Covid-19 pandemic, reductions of hospital admissions with a focus on emergencies have been observed for several medical and surgical conditions, while trend data during later stages of the pandemic are scarce. Consequently, this study aims to provide up-to-date hospitalization trends for several conditions including cardiovascular, psychiatry, oncology and surgery cases in both the in- and outpatient setting.Methods and findingsUsing claims data of 86 Helios hospitals in Germany, consecutive cases with an in- or outpatient hospital admission between March 13, 2020 (the begin of the "protection" stage of the German pandemic plan) and December 10, 2020 (end of study period) were analyzed and compared to a corresponding period covering the same weeks in 2019. Cause-specific hospitalizations were defined based on the primary discharge diagnosis according to International Statistical Classification of Diseases and Related Health Problems (ICD-10) or German procedure classification codes for cardiovascular, oncology, psychiatry and surgery cases. Cumulative hospitalization deficit was computed as the difference between the expected and observed cumulative admission number for every week in the study period, expressed as a percentage of the cumulative expected number. The expected admission number was defined as the weekly average during the control period. A total of 1,493,915 hospital admissions (723,364 during the study and 770,551 during the control period) were included. At the end of the study period, total cumulative hospitalization deficit was -10% [95% confidence interval -10; -10] for cardiovascular and -9% [-10; -9] for surgical cases, higher than -4% [-4; -3] in psychiatry and 4% [4; 4] in oncology cases. The utilization of inpatient care and subsequent hospitalization deficit was similar in trend with some variation in magnitude between cardiovascular (-12% [-13; -12]), psychiatry (-18% [-19; -17]), oncology (-7% [-8; -7]) and surgery cases (-11% [-11; -11]). Similarly, cardiovascular and surgical outpatient cases had a deficit of -5% [-6; -5] and -3% [-4; -3], respectively. This was in contrast to psychiatry (2% [1; 2]) and oncology cases (21% [20; 21]) that had a surplus in the outpatient sector. While in-hospital mortality, was higher during the Covid-19 pandemic in cardiovascular (3.9 vs. 3.5%, OR 1.10 [95% CI 1.06-1.15], PConclusionsThere have been varying changes in care pathways and in-hospital mortality in different disciplines during the Covid-19 pandemic in Germany. Despite all the inherent and well-known limitations of claims data use, this data may be used for health care surveillance as the pandemic continues worldwide. While this study provides an up-to-date analysis of utilization of hospital care in the largest German hospital network, short- and long-term consequences are unknown and deserve further studies.

BackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.MethodsPeripheral blood samples of 48 patients (62±10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 23 patients with left atrial low voltage areas (LVA), defined as ResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (qConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation.

BACKGROUND:Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical routine. Left atrial (LA) electro-anatomical remodelling in AF patients indicates disease progression and is associated with poor therapeutic success. PR interval prolongation is associated with an increased risk for AF, however, the association between LA remodelling measured as low voltage areas (LVA) during catheter ablation and PR interval is unknown. The aim of this study was to investigate the association between PR interval prolongation and LVA in AF patients. METHODS:We studied 103 patients (62±12 years, 59% males, 34% persistent AF) undergoing first AF catheter ablation and presenting with sinus rhythm. PR interval prolongation was defined as PR >200ms and analysed in resting ECG before intervention. LVA were determined using high-density maps and defined as

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Reported prevalence rates vary substantially between 1:500 (0.2%) and 1:3,000 (0.03%), which may be attributed to different study designs and population characteristics. Prevalence data for Germany is not available. Consequently, this study aimed (1) to quantify age- and gender-specific clinically diagnosed HCM prevalence in Germany based on the analysis of health care claims data of > 5 million insurants in 2015, and (2) to analyze temporal prevalence trends from 2011 to 2015.Data were extracted from the InGef (Insitute for Applied Health Research) database, which is an anonymized healthcare claims database with longitudinal data from patients insured in one of approximately 70 German social health insurances (SHIs). Patients were classified as HCM prevalent, if they had at least one verified ambulatory or one hospital main- or secondary discharge diagnosis of HCM (I42.1 or I42.2).In 2015, HCM was prevalent in 4,000 out of 5,490,810 patients (0.07%; 1:1,372). HCM prevalence increased gradually with age from 7.4/100,000 persons (95% CI 5.2-10.1) in 0-9 years old to 298.7/100,000 persons (95% CI 276.4-322.4) in patients > 80 years. In all age categories, men had a numerically higher prevalence than women with significant differences in patients > 30 years. There was a gradual annual prevalence increase from 75.8 (95% CI 75.2-76.4) in 2011 to 84.2 (95% CI 83.5-84.8) in 2015 per 100,000 persons.Overall, prevalence of clinically diagnosed HCM in Germany is lower than in systematic population studies based on echocardiographic diagnosis. Prevalence increased with advancing age and showed a constant yearly rise. Those observations may improve our understanding of the burden of this genetic heart disease on the health care system in Germany, increase the diagnostic awareness among clinicians and shape future screening and management strategies.

Arrhythmia recurrences after catheter ablation occur in up to 50% within one year but their prediction remains challenging. Recently, we developed a novel score for the prediction of rhythm outcomes after single AF ablation demonstrating superiority to other scores. The current study was performed to 1) prove the predictive value of the APPLE score in patients undergoing repeat AF ablation and 2) compare it with the CHADS2 and CHA2DS2-VASc scores.Rhythm outcome between 3-12 months after AF ablation were documented. The APPLE score (one point for Age >65 years, Persistent AF, imPaired eGFR (

Rare variants of genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF, which is in part based on the fact that "there is no therapeutic impact derived from AF genetic test results". However, there are no studies available supporting this recommendation. Consequently, this study analyzed the impact of rare variants affecting the cardiac sodium channel on rhythm outcome of AF catheter ablation.In 137 consecutive patients with lone AF enrolled in the Leipzig Heart Center AF ablation registry, screening for mutations in SCN5A, SCN1B - 4B, CAV3, GPD1L, SNTA1 and MOG1 was performed. We identified 3 rare non-synonymous variants in SCN5A, 5 in SCN1B, 1 in SCN4B, 1 in CAV3, 6 in GPD1L, 3 in SNTA1 and 3 in MOG1 (16%). Variant carriers were otherwise comparable with non-variant carriers. Analysis of AF recurrence rates after radiofrequency AF catheter ablation by serial 7-day Holter ECG monitoring between 3 and 12 months revealed no difference between groups, i.e. 45% in variant carriers vs. 49% in non-variant carriers.Rare variants in genes encoding the cardiac sodium channel and associated compounds are frequently found in lone AF but were not found to impact the outcome of AF catheter ablation. This finding supports current recommendations not to screen for rare variants for the ablation outcome in AF. Nevertheless, it may at least be helpful for understanding AF mechanisms and larger studies are needed to further explore the possible association between genotype and response to AF therapies.

Left atrial enlargement and persistent atrial fibrillation (AF) are well-known predictors for arrhythmia recurrence after AF catheter ablation (LRAF). In this study, by using pathway enrichment analysis of GWAS data, we tested the hypothesis that genetic pathways associated with these phenotypes are also associated with LRAF.Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing de-novo AF catheter ablation were genotyped for ~1,000,000 SNPs. SNPs found to be significantly associated with left atrial diameter (LAD) or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG). Associated genes were tested for pathway enrichment using WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), the Gene Annotation Tool to Help Explain Relationships (GATHER) and the databases provided by Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second step, the association of consistently enriched pathways and LRAF was tested.By using sequential 7-day Holter ECGs, LRAF between 3 and 12 months was observed in 48% and was associated with LAD (B = 1.801, 95% CI 0.760-2.841, p = 1.0E-3) and persistent AF (OR = 2.1; 95% CI 1.567-2.931, p = 2.0E-6). WebGestalt (adj. p = 2.7E-22) and GATHER (adj. p = 5.2E-3) identified the calcium signaling pathway (hsa04020) as the only consistently enriched pathway for LAD, while the extracellular matrix (ECM) -receptor interaction pathway (hsa04512) was the only consistently enriched pathway for AF type (adj. p = 2.1E-15 in WebGestalt; adj. p = 9.3E-4 in GATHER). Both calcium signaling (adj. p = 2.2E-17 in WebGestalt; adj. p = 2.9E-2 in GATHER) and ECM-receptor interaction (adj. p = 1.2E-10 in WebGestalt; adj. p = 2.9E-2 in GATHER) were significantly associated with LRAF.Calcium signaling and ECM-receptor interaction pathways are associated with LAD and AF type and, in turn, with LRAF. Future and larger studies are necessary to replicate and apply these findings.

BACKGROUND:Galectin-3 (Gal-3) is an emerging biomarker in heart failure that is involved in fibrosis and inflammation. However, its potential value as a prognostic marker in atrial fibrillation (AF) is unknown. The aim of this study was to assess the impact of AF catheter ablation on Gal-3 and evaluate its prognostic impact for predicting rhythm outcome after catheter ablation. METHODS:Gal-3 was measured at baseline and after 6 months using specific ELISA. AF recurrences were defined as any atrial arrhythmia lasting longer than 30 sec within 6 months after ablation. RESULTS:In 105 AF patients (65% males, age 62±9 years, 52% paroxysmal AF) undergoing catheter ablation, Gal-3 was measured at baseline and after 6 months and compared with an AF-free control cohort (n=14, 50 % males, age 58±11 years). Gal-3 was higher in AF patients compared with AF-free controls (7.8±2.9 vs. 5.8±1.8, ng/mL, p=0.013). However, on multivariable analysis, BMI (p=0.007) but not AF (p=0.068) was associated with Gal-3. In the AF cohort, on univariable analysis higher Gal-3 levels were associated with female gender (p=0.028), higher BMI (p=0.005) and both CHADS2 (p=0.008) and CHA2DS2-VASC (p=0.016) scores, however, on multivariable analysis only BMI remained significantly associated with baseline Gal-3 (p=0.016). Gal-3 was similar 6 months after AF catheter ablation and was not associated with sinus rhythm maintenance. CONCLUSIONS:Although galectin-3 levels are higher in AF patients, this is driven by cardiometabolic co-morbidities and not heart rhythm. Gal-3 is not useful for predicting rhythm outcome of catheter ablation.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is associated with inflammatory response, endothelial damage and with increased risk of thrombosis. However, whether these processes differ in peripheral and cardiac circulation is unknown. METHODS: Plasma markers (von Willebrand factor (vWf), soluble P-selectin (sPsel) and interleukin-6 (IL-6)) were measured by ELISA at three time points in 80 patients (62±10 years, 63% males, 41% paroxysmal AF) undergoing CA. These were at baseline--from femoral vein (FV) and left atrium (LA) before ablation; directly after ablation--from the pulmonary vein (PV), LA and FV; and 24 hours after procedure--from a cubital vein (CV). RESULTS: The levels of vWF and IL6--but not sP-sel--increased significantly 24 h after procedure (p

AIMS: This study investigated the possible association between hs-CRP as well as hs-CRP changes and rhythm outcome after AF catheter ablation. METHODS: We studied 68 consecutive patients with AF undergoing catheter ablation. hs-CRP levels were measured using commercially available assays before and 6 months after catheter ablation. Serial 7-day Holter ECGs were used to detect AF recurrences. RESULTS: Early AF recurrence (ERAF, within one week) was observed in 38%, while late AF recurrence (LRAF, between 3 and 6 months) occurred in 18% of the patients. None of the baseline clinical or echocardiographic variables was predictive of ERAF or LRAF. Baseline hs-CRP measured 2.07 ± 1.1 µg/ml and was not associated with ERAF and LRAF. At 6 months, hs-CRP levels were comparable with baseline values (2.14±1.19 µg/ml, p = 0.409) and were also not related with LRAF. However, patients with LRAF showed an hs-CRP increase from 2.03 ± 0.61 to 2.62 ± 1.52 µg/ml (p = 0.028). Patients with an hs-CRP change in the upper tertile (>0.2 µg/ml) had LRAF in 32% as opposed to 11% (p = 0.042) in patients in the lower (