Long-term outcomes following mitral valve replacement in children at heart center Leipzig: a 20-year analysis.

BACKGROUND: Although mitral valve repair is the preferred surgical strategy in children with mitral valve disease, there are cases of irreparable severe dysplastic valves that require mitral valve replacement. The aim of this study is to analyze long-term outcomes following mitral valve replacement in children in a tertiary referral center. METHODS: A total of 41 consecutive patients underwent mitral valve replacement between February 2001 and February 2021. The study data was prospectively collected and retrospectively analyzed. Primary outcomes were in-hospital mortality, long-term survival, and long-term freedom from reoperation. RESULTS: Median age at operation was 23 months (IQR 5-93), median weight was 11.3 kg (IQR 4.8-19.4 kg). One (2.4%) patient died within the first 30 postoperative days. In-hospital mortality was 4.9%. Four (9.8%) patients required re-exploration for bleeding, and 2 (4.9%) patients needed extracorporeal life support. Median follow-up was 11 years (IQR 11 months - 16 years). Long-term freedom from re-operation after 1, 5, 10 and 15 years was 97.1%, 93.7%, 61.8% and 42.5%, respectively. Long-term survival after 1, 5, 10 and 15 years was 89.9%, 87%, 87% and 80.8%, respectively. CONCLUSION: If MV repair is not feasible, MV replacement offers a good surgical alternative for pediatric patients with MV disease. It provides good early- and long-term outcomes.

Early and long-term outcomes following redo mitral valve surgery in patients with prior minimally invasive mitral valve surgery.

OBJECTIVES: The frequency of minimally invasive mitral valve surgery (MVS) has steadily increased over the last decades and therefore surgeons are now encountering an increasing number of patients requiring mitral valve (MV) reoperations post-minimally invasive MVS. The aim of this study was to analyse the early postoperative outcomes and the long-term survival in patients who undergo reoperative MVS following previous minimally invasive surgery. METHODS: Patients who underwent redo MVS following prior minimally invasive MVS between January 2002 and December 2021 were included in our analysis. Study data were prospectively collected and retrospectively analysed. The primary outcomes were 30-day mortality and long-term survival. RESULTS: Among the 187 included patients, 34 (18.2%) underwent repeat MV repair and 153 (81.8%) MV replacement. The median age was 66 years (interquartile range 56-74) and 80 (42.8%) patients were female. Redo MVS was performed through median sternotomy in 169 patients (90.4%). A total of 77 (41.2%) patients had additional concomitant procedures. The median intensive care unit stay was 1 day (1-5). The 30-day mortality was 6.4% (12/187). Estimated survival at 5 and 12 years was 61.8% and 38.3%, respectively. Preoperative stroke (hazard ratio 3.28, 95% confidence interval 1.37-7.85, P = 0.007) as well as infective endocarditis (hazard ratio 1.85; 95% confidence interval 1.09-3.11, P = 0.021) were independent predictors of long-term mortality. CONCLUSIONS: Redo MVS following prior minimally invasive MVS can be performed safely with low early perioperative mortality and acceptable long-term survival. Preoperative stroke, infective endocarditis and concomitant tricuspid valve surgery are independent predictors of long-term mortality.

Long-Term Results Following Combined Repair of Atrioventricular Septal Defect with Tetralogy of Fallot.

Atrioventricular septal defect (AVSD) in association with tetralogy of Fallot (TOF) is a rare and complex congenital cardiac malformation. We report our institutional experience and outcomes following surgical correction over a 20-year period. Patients who underwent combined surgical AVSD and TOF correction between October 2001 and February 2020 were included for analysis. All patients underwent primary repair. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were in-hospital mortality and long-term freedom from reoperation. During the study period, a total of 10 consecutive patients underwent combined surgical AVSD and TOF correction. Median age at operation was 307 days (IQR 228-457) and median weight was 7.7 kg (IQR 6.7-9.5). Down Syndrome was present in six of the patients. In-hospital mortality was 0%. One patient required re-exploration due to bleeding. Median follow-up was 11 years (IQR 11 months -16 years). There was one case of reoperation due to significant residual ventricular septal defect after 2 months. None of the patients died during follow-up. Combined primary AVSD and TOF repair can be performed with low early mortality and morbidity, as well as a high long-term freedom from reoperation.

Long-term results following atrioventricular septal defect repair.

BACKGROUND: Atrioventricular septal defects (AVSD) represent 4-7% of congenital cardiac malformations. Definitive early repair is favored over prior pulmonary artery banding and delayed definitive repair in many centers. The aim of this study was to analyze long-term outcomes following AVSD repair over a 21-year period. METHODS: A total of 202 consecutive patients underwent surgical AVSD correction between June 1999 and December 2020. Surgery was performed using the double-patch technique. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were In-hospital mortality and overall long-term freedom from reoperation. RESULTS: Median age at operation was 120 days (IQR 94-150), median weight was 5.0 kg (4.2-5.3). None of the patients died within the first 30 postoperative days. In-hospital mortality was 0.5% (1/202 patients). Median follow-up was 57 months (11-121). Overall freedom from reoperation at 5, 10 and 15 years was 91.8%, 86.9% and 86.9%, respectively. CONCLUSION: AVSD repair with the double-patch technique is a safe and effective procedure with good early postoperative outcomes and low long-term reoperation rates.

Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance.

For a majority of patients with non-small cell lung cancer with EGFR mutations, treatment with EGFR inhibitors (EGFRi) induces a clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to disease relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister cells and deciphering how drug-tolerant cells evolve in response to treatment could help identify strategies to improve the efficacy of EGFRi. In this study, we tracked the origins and clonal evolution of drug-tolerant cells at a high resolution by using an expressed barcoding system coupled with single-cell RNA sequencing. This platform enabled longitudinal profiling of gene expression and drug sensitivity in response to EGFRi across a large number of clones. Drug-tolerant cells had higher expression of key survival pathways such as YAP and EMT at baseline and could also differentially adapt their gene expression following EGFRi treatment compared with sensitive cells. In addition, drug combinations targeting common downstream components (MAPK) or orthogonal factors (chemotherapy) showed greater efficacy than EGFRi alone, which is attributable to broader targeting of the heterogeneous EGFRi-tolerance mechanisms present in tumors. Overall, this approach facilitates thorough examination of clonal evolution in response to therapy that could inform the development of improved diagnostic approaches and treatment strategies for targeting drug-tolerant cells. SIGNIFICANCE: The evolution and heterogeneity of EGFR inhibitor tolerance are identified in a large number of clones at enhanced cellular and temporal resolution using an expressed barcode technology coupled with single-cell RNA sequencing.

Very late arrhythmia recurrences in patients with sinus rhythm within the first year after catheter ablation: The Leipzig Heart Center AF Ablation Registry.

AIMS: Arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) still remain an important management issue. Recently, the APPLE score had been introduced to predict rhythm outcomes within 12 months after catheter ablation, while the simple MB-LATER score was developed for the prediction of very late recurrence of AF (VLRAF) occurring after 12 months. The aim of this study was to compare APPLE and MB-LATER scores in predicting VLRAF. METHODS AND RESULTS: The study population included arrhythmia-free patients within first 12 months after first radiofrequency catheter ablation from The Heart Center Leipzig AF Ablation Registry. The APPLE [one point for Age >65 years, Persistent AF, imPaired eGFR <60 mL/min/1.73 m2, Left atrial (LA) diameter ≥43 mm, EF <50%] and MB-LATER scores [one point for Male gender, Bundle branch block or QRS >120 ms, LA diameter ≥47 mm, AF Type (persistent AF), Early Recurrence <3 months] were calculated before and 3 months after ablation, respectively. We followed 482 patients {age 61 [interquartile range (IQR) 54-68] years, 66% males, 32% persistent AF} for median 40 (IQR 35-50) months. There were 184 patients (38.3%) with arrhythmia recurrences within 13-60 months after ablation. On multivariate analysis, APPLE [odds ratio (OR) 1.517, 95% confidence interval (CI) 1.244-1.850, P < 0.001] and MB-LATER (OR 1.437, 95% CI 1.211-1.705, P < 0.001) scores and diabetes mellitus (OR 2.214, 95% CI 1.353-3.625, P = 0.002) were significantly associated with arrhythmia recurrences. Receiver operating characteristic curve analyses demonstrated moderate prediction for both scores [area under the curve (AUC) 0.607, P < 0.001 for APPLE score, AUC 0.604, P < 0.001 for MB-LATER]. CONCLUSION: Prediction of VLRAF is similar for both APPLE and MB-LATER scores. A better score remains still a clinical unmet need.

Time-dependent prediction of arrhythmia recurrences during long-term follow-up in patients undergoing catheter ablation of atrial fibrillation: The Leipzig Heart Center AF Ablation Registry.

The prediction of arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) remains challenging. The aim of current analysis was to investigate the time-dependent prediction of arrhythmia recurrences after AF catheter ablation during long-term follow-up. The study included 879 patients (61 ± 10 years; 64% males; 39% persistent AF) undergoing first AF catheter ablation. Rhythm outcomes were documented using 7-days Holter monitoring. The APPLE score (Age, Persistent AF, imPaired eGFR, Left atrium (LA), EF) was calculated at baseline, while MB-LATER score (Male gender, Bundle branch block, LA, AF Type, Early Recurrences) 3 months after ablation. The median follow-up time was 37 months [95%CI 35;39]. ERAF and LRAF occurred in 45% and 64%, respectively. On multivariable analysis, ERAF (HR 2.095, 95%CI 1.762-2.490, p < 0.001) was strongly associated with LRAF. The APPLE (HR 1.385, 95%CI 1.276-1.505, p < 0.001) and MB-LATER (HR 1.326, 95%CI 1.239-1.419, p < 0.001) scores significantly predicted LRAF during follow-up. On the ROC analysis, APPLE (AUC 0.640, 95%CI 0.602-0.677, p < 0.001) and MB-LATER (AUC 0.654, 95%CI 0.616-0.691, p < 0.001) demonstrated moderate prediction. Summarizing, ERAF was the strongest predictor for LRAF in time-dependent manner. The APPLE and MB-LATER scores demonstrated moderate prediction of arrhythmia recurrences during long term follow-up.

Prediction of electro-anatomical substrate using APPLE score and biomarkers.

AIMS: Low voltage areas (LVAs) represent advanced remodelling processes in left atrium in patients with atrial fibrillation (AF) and are associated with higher rates of arrhythmia recurrences. However, the prediction of LVA based on clinical parameters is understudied. Recently, we introduced APPLE score to predict rhythm outcomes after catheter ablation. The aim of this study was to analyse (i) LVA prediction using APPLE score and (ii) differences in biomarker profiles according to APPLE score in AF patients. METHODS AND RESULTS: Patients undergoing first AF ablation were included. The APPLE score (one point for Age >65 years, Persistent AF, imPaired eGFR <60 mL/min/1.73 m2, LA diameter ≥43 mm, EF <50%) was calculated before ablation. Blood plasma samples from femoral vein were collected before ablation. Low voltage area were determined using high-density maps and defined as <0.5 mV. NT-proANP, NT-proBNP, L-Selectin, and vascular cell adhesion protein 1 (VCAM-1) were studied using commercially available assays. We studied 214 patients [age median (interquartile range) 65 (57-72) years, 59% males, 59% persistent AF, 27% LVA]. There were 42% patients with APPLE ≥3. The levels of NT-proANP (P < 0.001), NT-proBNP (P = 0.016), and VCAM-1 (P = 0.040) increased with each APPLE point. In the univariable analysis, APPLE score [odds ratio (OR) 1.921, 95% confidence interval (CI) 1.453-2.538; P < 0.001], female gender (OR 2.283, 95% CI 1.280-4.071; P = 0.005), and NT-proANP (OR 1.031, 95% CI 1.008-1.054; P = 0.007) were significant predictors for LVA. On the multivariable analysis, only APPLE score and female gender remained associated with LVA. CONCLUSION: The APPLE score can be used for prediction of LVA before AF ablation. There was a positive correlation between biomarker levels and APPLE score.

Clinical scores used for the prediction of negative events in patients undergoing catheter ablation for atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults. Catheter ablation (CA) is one of the most important management strategies to reduce AF burden and AF-associated complications. In order to stratify the risk of adverse events and to predict treatment success in AF patients undergoing CA, several risk stratification scores had been developed during the last decade. The aim of this review is to provide an overview of the most important clinical risk scores predicting rhythm outcomes, electro-anatomical substrate and mortality in AF.

Association between PR interval prolongation and electro-anatomical substrate in patients with atrial fibrillation.

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 <0.5 mV. RESULTS: There were 24 patients (23%) with PR interval prolongation and 18 patients (17%) with LVA. There were significant correlations between PR prolongation with LVA, CHA2DS2-VASc score and eGFR (r2 = 0.230, 0.216, and 0.307, all p<0.05). PR interval prolongation (OR 3.450, p = 0.024), persistent AF (OR 5.391, p = 0.002), and LA size (OR 1.117, p = 0.018) were significant predictors for LVA, while age (OR 1.072, p = 0.005), LVA (OR 3.450 p = 0.024) and eGFR (OR 0.962, p = 0.004) were associated with PR interval prolongation. CONCLUSIONS: Beside persistent AF and LA size, PR interval prolongation might be useful for the prediction of electro-anatomical substrate in AF patients. Larger studies are needed to confirm these results.

Association Between Cardiovascular Magnetic Resonance-Derived Left Atrial Dimensions, Electroanatomical Substrate and NT-proANP Levels in Atrial Fibrillation.

Background Enlargement of left atrial ( LA ) size indicates advanced disease stage in patients with atrial fibrillation ( AF ) and is associated with poor success of different AF therapies. Two dimensional echocardiographic LA measurements do not reliably reflect the true size of LA anatomy. The aim of the current study was: 1) to analyze cardiovascular magnetic resonance ( CMR )-derived LA dimensions and their association with low voltage areas ( LVA ); and 2) to investigate the association between these parameters and NT -pro ANP (N-terminal proatrial natriuretic peptide) levels. Methods and Results Patients undergoing first AF catheter ablation were included. All patients underwent CMR imaging (Ingenia 1.5T Philips) before intervention. CMR data ( LA volume, superior-inferior, transversal and anterior-posterior LA diameters) were measured in all patients. LVA were determined using high-density maps and a low voltage threshold <0.5 mV. Blood plasma samples from femoral vein were collected before catheter ablation. NT -pro ANP levels were studied using commercially available assays. There were 216 patients (65±11 years, 59% males, 56% persistent AF , 26% LVA ) included into analyses. NT -pro ANP levels in patients with LVA were significantly higher than in those without (median/interquartile range 22 [13-29] versus 15 [9-22] pg/mL, P=0.004). All CMR derived LA diameters correlated significantly with persistent AF ( r²=0.291-0.468, all P<0.001), LVA ( r²=0.187-0.306, all P<0.001), and NT -pro ANP levels ( r²=0.258-0.352, P<0.01). On logistic regression multivariable analysis, age (odds ratio=1.090, 95% confidence interval: 1.030-1.153, P=0.003), females (odds ratio=2.686, 95% confidence interval: 1.047-6.891, P=0.040), and LA volume (odds ratio=1.022, 95% confidence interval: 1.009-1.035, P=0.001) remained significant predictors for LVA . Conclusions Left atrial CMR parameters are associated with persistent AF , low voltage areas and NT -pro ANP levels. LA volume is the most significant predictor for LVA .

Heart Failure and Stroke.

PURPOSE: Ischemic stroke significantly contributes to morbidity and mortality in heart failure (HF). The risk of stroke increases significantly, with coexisting atrial fibrillation (AF). An aggravating factor could be asymptomatic paroxysms of AF (so-called silent AF), and therefore, the risk stratification in these patients remains difficult. This review provides an overview of stroke risk in HF, its risk stratification, and stroke prevention in these patients. RECENT FINDINGS: Stroke risk stratification in HF patients remains an important issue. Recently, the CHA2DS2-VASc score, originally developed to predict stroke risk in AF patients, had been reported to be a predictive for strokes in HF patients regardless of AF being present. Furthermore, there are several independent risk factors (e.g., hypertension, diabetes mellitus, prior stroke) described. Based on the current evidence, HF should be considered as an independent risk factor for stroke. The CHA2DS2-VASc score might be useful to predict stroke risk in HF patients with or without AF in clinical routine. However, there is only a recommendation for the oral anticoagulation use in patients with concomitant HF and AF, while in patients with HF and no AF, individualized risk stratification is preferred. Current guidelines recommend to prefer non-vitamin Kantagonist anticoagulants over warfarin.

Prediction of electro-anatomical substrate and arrhythmia recurrences using APPLE, DR-FLASH and MB-LATER scores in patients with atrial fibrillation undergoing catheter ablation.

Arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) cause intensive treatment costs. Left atrial electro-anatomical remodeling measured as low voltage areas (LVA) during catheter ablation indicates advanced disease stage and is associated with poor ablation success. The aim of this study was to analyze the prediction of LVA and arrhythmia recurrences using APPLE, DR-FLASH and MB-LATER scores. APPLE, DR-FLASH scores were calculated at baseline and MB-LATER at 3 months post-ablation in AF patients undergoing first catheter ablation. LVA was determined using high-density maps and defined as <0.5 mV. Early (ERAF, <3 months) and late (LRAF, 3-12 months) were analyzed during follow-up. The study population included 241 patients (age 64 ± 11 years, 59% males, 59% persistent AF, 27% LVA, 27% LRAF). LVA were significantly associated with recurrences (OR 2.081, p = 0.026). While on univariable analysis, all scores were significantly associated with LVA, on multivariable analysis only APPLE (OR 1.789, p < 0.001) and DR-FLASH (OR 2.144, p < 0.001) remained significant predictors. However, MB-LATER (OR 1.445, p = 0.034) and ERAF (OR 5.078, p < 0.001) remained associated with LRAF on the multivariable analysis. These results were validated in a subgroup of 873 patients (age 61 ± 10, 63% males, 39% persistent AF, 34% LRAF, 27% LVA) from The Leipzig Heart Center AF Ablation Registry. All scores were significantly associated with recurrences. However, ERAF was the most powerful predictor for later rhythm outcomes. Summarizing, a clinical score useful for prediction for both LVA and rhythm outcomes in AF patients remains a clinical unmet need.

[Biomarkers and atrial fibrillation : Prediction of recurrences and thromboembolic events after rhythm control management]. / Biomarker und Vorhofflimmern : Vorhersage von Rezidiven und thromboembolischen Ereignissen nach rhythmuserhaltender Therapie.

Atrial fibrillation (AF) is the most common arrhythmia in clinical praxis and is associated with an increased risk for cardio- and cerebrovascular complications leading to an increased mortality. Catheter ablation represents one of the most important and efficient therapy strategies in AF patients. Nevertheless, the high incidence of arrhythmia recurrences after catheter ablation leads to repeated procedures and higher treatment costs. Recently, several scores had been developed to predict rhythm outcomes after catheter ablation. Biomarker research is also of enormous interest. There are many clinical and blood biomarkers pathophysiologically associated with AF occurrence, progression and recurrences. These biomarkers-including different markers in blood (e. g. von Willebrand factor, D­dimer, natriuretic peptides) or urine (proteins, epidermal grown factor receptor) but also cardiac imaging (echocardiography, computed tomography, magnetic resonance imaging)-could help to improve clinical scores and be useful for individualized AF management and optimized patients' selection for different AF treatment strategies. In this review, the role of diverse biomarkers and their predictive value related to AF-associated complications are discussed.

Role of NT-proANP and NT-proBNP in patients with atrial fibrillation: Association with atrial fibrillation progression phenotypes.

BACKGROUND: Electroanatomic remodeling in atrial fibrillation (AF) leads to disease initiation and perpetuation. Although atrial natriuretic peptide (ANP) is specifically expressed in the atria and is involved in atrial remodeling, B-type natriuretic peptide (BNP) is associated with mortality and cardiovascular events in AF. OBJECTIVE: The purpose of this study was to investigate the association between N-terminal (NT)-proBNP and NT-proANP levels with 3 AF progression phenotypes: persistent AF, left atrial diameter (LAD) dilation, and left atrial low-voltage areas (LVAs). METHODS: We studied NT-proBNP and NT-proANP in a discovery cohort (n = 51) and replicated the findings in a validation cohort (n = 241) undergoing first AF catheter ablation. Blood plasma samples from femoral vein were collected before catheter ablation. LVAs were determined using high-density maps and defined as <0.5 mV. RESULTS: In our pilot cohort (age 62 ± 10 years; 63% male; 59% persistent AF; 22% LVA), NT-proANP-but not NT-proBNP-levels were significantly higher in LVA patients (14.1 vs 8.6 ng/mL; P = .009) and correlated with LAD (r2 = 0.362; P = .011). These results were replicated in the validation cohort (age 64 ± 11 years; 59% male; 59% persistent AF; 27% LVA) (12.7 vs 8.8 ng/mL; P = .016) and correlated with LAD (r2 = 0.180; P = .019). NT-proANP levels increased according to 4 disease progression groups: paroxysmal AF without LVA, persistent AF without LVA, paroxysmal AF with LVA, and persistent AF with LVA (mean 15, 20, 19, and 27 ng/mL, respectively; P = .004). CONCLUSION: Natriuretic peptides show different sensitivity for phenotypes of AF progression. The clinical impact of NT-proANP in refining individualized therapy and disease prevention should be addressed in larger studies.

Characteristics of PR interval as predictor for atrial fibrillation: association with biomarkers and outcomes.

The PR interval may be considered as a simple and easily obtainable predictor for adverse events, including atrial fibrillation (AF), pacemaker implantation, and mortality. Interestingly, both high and low extremes of the PR duration are associated with AF risk. However, the results regarding PR prolongation as a risk factor for AF are inconsistent. Some studies have analyzed the impact of P duration (as a part of the PR interval) and demonstrated that the P-duration contributes to the length of PR interval and adverse outcomes. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by myocardial fibrosis and vascular inflammation. Furthermore, due to PR prolongation chronically raised intra-atrial pressure and consequential neuro-hormonal activation predispose systemic vascular endothelial dysfunction and explain the associations with adverse vascular events. In this review, we discuss the association between biomarkers with PR interval in AF.

[Improving the visibility of rare diseases in health care systems by specific routine coding]. / Verbesserung der Sichtbarkeit seltener Erkrankungen in Gesundheitssystemen durch spezifische Routinekodierung.

The evaluation of healthcare providers' routine data is an important basis for the analysis, planning and evaluation of measures in public health. The representation of rare diseases in the classifications that are used to record health data is not adequate. Coding rare diseases in a specific way is a challenge all around the world. There is still no general international solution for the routine coding of rare diseases.The double coding of rare diseases with ICD-10 Codes and Orphacodes is a short-term and low-cost alternative solution. Furthermore, this double coding enables international comparability. The specific encoding of rare diseases through this double coding can improve their capturing for statistical analysis and thus their visibility in healthcare systems. Nevertheless, the provision of a new classification is not enough to gather valid data. Some measures have already been adopted in Germany (and at the European level) in order to support the implementation of this double coding. Subsequently it would be possible to adopt more specific public health measures, based on better data, in order to provide better care to the more than four million people in Germany affected by rare diseases.