Community-based analysis of stroke prevention and effect of public interventions in atrial fibrillation: results from the ARENA project.

BACKGROUND: Community-based interventions may promote awareness and adherence to atrial fibrillation (AF)-related therapies, potentially reducing adverse events. The ARENA project investigated the health status, therapies and events in AF patients in the Rhein-Neckar Region, Germany. The subproject "ARENA intervention" studied the effect of community-based interventions on AF-associated outcomes. METHODS: From 2016 onward, patients with diagnosed AF were recruited for the observational ARENA registry. In 2018, an intervention period was initiated involving population-based information campaigns on AF diagnosis and therapies. The "control group" was recruited prior to initiation, and the "intervention group" afterward. Patients underwent standardized follow-up > 1 year after recruitment. Clinical outcomes, therapy and quality of life were compared between the two groups. RESULTS: A total of 2769 patients were included. This real-world cohort showed high adherence to oral anticoagulation therapy (OAC) and an increased use of NOACs over vitamin K antagonists over time. In the intervention group (n = 1362), more patients continued OAC at follow-up (87.1% vs. 81.5%, P = 0.002). However, this difference was not significant in the patient subgroup with class I/IIa indications for OAC (90.1% vs. 87.5%, P = 0.11). AF-related re-hospitalization was lower in the intervention group (6.8% vs. 12.3%, P < 0.001). There was no significant difference in quality of life. AF-related anxiety was reduced at follow-up. Of note, nearly a quarter of all patients stated that ARENA had influenced their health perception. CONCLUSION: Tailored community-based campaigns may raise awareness for AF-related health issues, supporting therapy adherence. Future public strategies to improve quality of life in AF patients should be investigated, as the ARENA project hints at a potential benefit of population-based campaigns. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02978248).

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

AIMS: Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. METHODS: Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6-12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6-12 months using two established methods: reference change value (RCV) and minimal important difference (MID). RESULTS: Median baseline hs-cTnT concentrations were 34.4 ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6 months (IQR: 6-7). Median concentration change was 1.9 ng/L (IQR: 0.7-3.2) and 0.8 ng/L (IQR: 0-7.0) at 60 min and 6-9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT ≥ 52 ng/L. Biological variabilities at 6-12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. CONCLUSIONS: The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. METHODS AND RESULTS: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p = .008). CONCLUSIONS: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous.

Catheter-based ablation to improve outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction: Rationale and design of the CABA-HFPEF-DZHK27 trial.

AIMS: Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation-based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA-HFPEF-DZHK27 (CAtheter-Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF. METHODS: CABA-HFPEF-DZHK27 (NCT05508256) is an investigator-initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two-sided alpha = 0.05, 1-beta = 0.8). CONCLUSION: CABA-HFPEF-DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF.

Increased expression of human endogenous retrovirus K in endomyocardial biopsies from patients with cardiomyopathy - a transcriptomics meta-analysis.

Most studied, investigating transcriptional changes in myocardial biopsies focus on human genes. However, the presence and potential consequence of persistent expression of viral genes within the myocardium is unclear. The aim of the study was to analyze viral gene expression in RNAseq data from endomyocardial biopsies. The NCBI Bioproject library was screened for published projects that included bulk RNA sequencing data from endomyocardial biopsies from both healthy and diseased patients with a sample size greater than 20. Diseased patients with hypertrophic, dilated, and ischemic cardiomyopathies were included. A total of 507 patients with 507 samples from 6 bioprojects were included and mapped to the human genome (hg38). Unmappable sequences were extracted and mapped to an artificial 'super-virus' genome comprising 12,182 curated viral reference genomes. Subsequently, the sequences were reiteratively permutated and mapped again to account for randomness. In total, sequences from 68 distinct viruses were found, all of which were potentially human pathogenic. No increase in cardiotropic viruses was found in patients with dilated cardiomyopathy. However, the expression levels of the particle forming human endogenous retrovirus K were significantly increased (q < 0.0003, ANOVA). Higher expression levels were associated with increased expression in mitochondrial pathways such as oxidative phosphorylation (p < 0.0001). In Conclusion, expression of human endogenous retrovirus K is significantly increased in patients with dilated cardiomyopathy, which in turn was associated with transcriptional alterations in major cellular pathways.

Syncope due to recurrent ventricular tachycardias after transcatheter aortic valve implantation with unexpected diagnosis in cardiac computed tomography: a case report.

Background: Delayed coronary obstruction (DCO) is a rare but potentially life-threatening complication after transcatheter aortic valve implantation (TAVI) mostly affecting the left main coronary artery (LMCA) and often caused by prosthesis endothelialization or thrombus formations. Herein, we report an unusual case of a delayed LMCA-obstruction caused by a calcium nodule, which was diagnosed 4 months after TAVI due to recurrent ventricular tachycardia (VT) episodes. Case summary: A 73-year-old patient was readmitted to an external hospital with syncope three months after TAVI. Fast VT could be induced in electrophysiological examination, why the patient received a two-chamber implantable cardioverter defibrillator (ICD). However, after 1 month the patient was readmitted to our department with another syncope. Implantable cardioverter defibrillator records revealed multiple fast VT episodes (200-220 b.p.m.). In addition, the patient reported new-onset exertional dyspnoea (New York Class Association Stage III) and elevated high-sensitive cardiac troponin of 115 ng/L. Due to the symptoms and laboratory markers indicating potential myocardial ischaemia, a cardiac computed tomography angiography (CCTA) was performed. Cardiac computed tomography angiography revealed obstruction of the LMCA likely caused by calcium shift during TAVI. After CCTA-guided percutaneous coronary intervention, patient's course remained uneventful. Discussion: The present case report highlights the role of CCTA as a powerful non-invasive diagnostic tool in complex settings after TAVI. Delayed coronary obstruction as a procedural complication can occur after TAVI and manifest with various symptoms, including new-onset or recurrent VTs, like in the present case. Cardiac computed tomography angiography provided accurate assessment of the implanted prosthesis and detection of DCO, thus guiding the subsequent PCI.

Personalized care in dilated cardiomyopathy: Rationale and study design of the activeDCM trial.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, particularly in younger individuals. Low physical strength is a global risk factor for cardiovascular mortality, and physical activity and a healthy lifestyle have been shown to improve outcomes in patients with heart failure. However, inappropriate exercise may increase the risk of arrhythmias in certain individuals with DCM. The determinants for predicting individual risks in this setting are poorly understood, and clinicians are hesitant to recommend sports for cardiomyopathy patients. The activeDCM trial aims to assess the safety and efficacy of a personalized exercise and activity programme for individuals with DCM. STUDY DESIGN: The activeDCM trial is a prospective, randomized, interventional trial with a 12 month follow-up. Three hundred patients, aged 18-75 years with DCM, left ventricular ejection fraction (LVEF) ≤ 50% and New York Heart Association (NYHA) classes I-III, will be enrolled. The intervention includes a personalized exercise and activity programme. The primary outcome is the increase in peak oxygen uptake (VO2max, mL/kg/min) from baseline to 12 months. Secondary endpoints include adherence to personalized activity programmes, freedom from clinically relevant arrhythmia, unplanned hospitalization for heart failure and changes in NYHA class, quality of life scores, 6 min walk distance, muscular strength, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels and cardiac function. Advanced research questions include high-density phenome and omics analysis combined with digital biomarkers derived from Apple Watch devices. DISCUSSION: The activeDCM trial will provide valuable insights into the safety and efficacy of personalized exercise training in DCM patients, inform clinical practice and contribute to the development of heart failure management programmes. The study will generate data on the impact of exercise on various aspects of cardiovascular disease, including genetic, metabolic, phenotypic and longitudinal aspects, facilitating the development of future digital tools and strategies, including the incorporation of smart wearable devices.

Recognition of psychological comorbidity and psychotherapeutic treatment status of ventricular assist device patients.

BACKGROUND: Due to its high impact on quality of life and mental health, close monitoring and often psychotherapy is recommended for patients with a ventricular assist device (VAD). This study investigates the psychological comorbidity and the corresponding psychotherapeutic treatment situation of VAD patients. Special attention is also given to the professional perspective VAD team (assistant and senior cardiologists and specialized nurses). METHODS: We conducted a cross-sectional observational study. Data from 50 VAD patients (mean age = 53.52, standard deviation = 13.82 years, 84.0% male) and their VAD team were analyzed. The presence of a psychological disorder was evaluated by structured clinical interviews for DSM-IV (SCID-I-Interviews). Patients answered a questionnaire regarding their current psychotherapeutic treatment status and their attitude towards psychotherapy. The VAD team answered a questionnaire about the patients' needs for psychotherapy and indicated whether they addressed this topic with the patient. Data were analyzed descriptively, by analysis of variance and t-test. RESULTS: A total of 58% of VAD patients suffered from at least one significant psychological disorder, 79.3% of those were not in psychotherapy. The VAD team could not identify the patients who suffered from a psychological disorder (F = 1.90; p = 0.18). They perceived more need for psychotherapy than they addressed with their patients (T = 3.39; p < 0.001). CONCLUSIONS: While there is a high psychological morbidity among VAD patients, only few receive psychotherapy. Psychological comorbidity is not easily detected by the VAD team. Standardized psychosocial care could be implemented by regular psychological assessments and further information of patients and their VAD teams.

CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.

Cardiac signaling pathways functionally important in the heart's response to exercise often protect the heart against pathological stress, potentially providing novel therapeutic targets. However, it is important to determine which of these pathways can be feasibly targeted in vivo. Transgenic overexpression of exercise-induced CITED4 has been shown to protect against adverse remodeling after ischemia/reperfusion injury (IRI). Here we investigated whether somatic gene transfer of CITED4 in a clinically relevant time frame could promote recovery after IRI. Cardiac CITED4 gene delivery via intravenous AAV9 injections in wild type mice led to an approximately 3-fold increase in cardiac CITED4 expression. After 4 weeks, CITED4-treated animals developed physiological cardiac hypertrophy without adverse remodeling. In IRI, delivery of AAV9-CITED4 after reperfusion resulted in a 6-fold increase in CITED4 expression 1 week after surgery, as well as decreased apoptosis, fibrosis, and inflammatory markers, culminating in a smaller scar and improved cardiac function 8 weeks after IRI, compared with control mice receiving AAV9-GFP. Somatic gene transfer of CITED4 induced a phenotype suggestive of physiological cardiac growth and mitigated adverse remodeling after ischemic injury. These studies support the feasibility of CITED4 gene therapy delivered in a clinically relevant time frame to mitigate adverse ventricular remodeling after ischemic injury.

Assessing the Applicability of Cardiac Myosin Inhibitors for Hypertrophic Cardiomyopathy Management in a Large Single Center Cohort.

Background: Cardiac myosin inhibitors (CMIs), including Mavacamten and Aficamten, have emerged as a groundbreaking treatment for hypertrophic cardiomyopathy (HCM). The results from phase 2 and 3 randomized clinical trials for both drugs have showed promising outcomes. However, the highly selective patient recruitment for these trials raises questions about the generalizability of the observed positive effects across broader patient populations suffering from HCM. Methods: A retrospective cohort study at University Hospital Heidelberg included 404 HCM patients. Baseline assessments included family history, electrocardiograms (ECGs), and advanced cardiac imaging, to ensure the exclusion of secondary causes of left ventricular hypertrophy. Results: Among the HCM patients evaluated, only a small percentage met the inclusion criteria for recent CMI trials: 10.4% for EXPLORER-HCM and 4.7% for SEQUOIA-HCM. The predominant exclusion factor was the stringent left ventricular outflow tract (LVOT) gradient requirement. Conclusions: This study highlights a significant discrepancy between patient demographics in clinical trials and those encountered in routine HCM clinical practice. Despite promising results from the initial randomized clinical trials that led to the approval of Mavacamten, the selected patient population only represents a small part of the HCM patient cohort seen in routine clinics. This study advocates for further expanded randomized clinical trials with broader inclusion criteria to represent diverse primary HCM patient populations.

Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study.

AIM: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). METHODS: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. RESULTS: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001). CONCLUSION: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. GERMAN CLINICAL TRIALS REGISTER: DRKS00031954.

Comparative Assessment of Percutaneous Left-Atrial Appendage Occlusion (LAAO) Devices-A Single Center Cohort Study.

BACKGROUND: Percutaneous left-atrial appendage closure (LAAC) is an established method for preventing strokes in patients with atrial fibrillation, offering an alternative to oral anticoagulation. Various occluder devices have been developed to cater to individual anatomical needs and ensure a safe and effective procedure. In this retrospective, monocentric cohort study, we compare different LAAO devices with respect to clinical outcomes, LAA sealing properties, and device-related complications. METHODS: We conducted a retrospective analysis of 270 patients who underwent percutaneous LAA closure in our center between 2009 and 2023. Patient data were extracted from medical records, including gender, age at implantation, indication, device type and size, laboratory values, LAA anatomy, periprocedural complications, ECG parameters, transthoracic and transesophageal echocardiography parameters (TTE and TEE), as well as medication at discharge. Moreover, fluoroscopy time and implantation duration, as well as post-implantation clinical events up to 1 year, were collected. Endpoints were bleeding events, recurrent stroke, thrombi on devices, and death. RESULTS: The implanted devices were the Watchman 2.5, Watchman FLX, Amplatzer Cardiac Plug (ACP), and Amulet. The procedural success rate was 95.7% (n = 265), with cactus anatomy posing the most challenges across all devices. The mean patient age was 75.5 ± 7.7 years, with 64.5% being male. The median CHA2DS2-VASc score was 4.8 ± 1.5 and the median HAS-BLED score was 3.8 ± 1.0. Indications for LAA closure included past bleeding events and elevated bleeding risk. Periprocedural complications were most commonly bleeding at the puncture site, particularly after ACP implantation (p = 0.014). Significant peridevice leaks (PDL) were observed in 21.4% of simple sealing mechanism devices versus 0% in double sealing mechanism devices (p = 0.004). Thrombi were detected on devices in six patients, with no subsequent ischemic stroke or thromboembolic event. Comparative analysis revealed no significant differences in the occurrence of stroke, transient ischemic attack (TIA), thromboembolic events, device-related thrombi, or mortality among different device types. A 62.3% relative risk reduction in thromboembolic events and 38.6% in major bleedings could be observed over 568.2 patient years. CONCLUSIONS: In summary, our study highlights the efficacy and safety of LAA closure using various occluder devices despite anatomical challenges. Our long-term follow-up findings support LAA closure as a promising option for stroke prevention in selected patient cohorts. Further research is needed to refine patient selection criteria and optimize outcomes in LAA closure procedures.

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology.

BACKGROUND: Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood. OBJECTIVE: We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression. METHODS: After exposure to 20 Gy of x-rays in a single fraction, neonatal rat ventricular cardiomyocytes were analyzed 24 and 96 hours postradiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration in both monolayers and single cells. In addition, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and messenger RNA levels. RESULTS: After irradiation with 20 Gy, neonatal rat ventricular cardiomyocytes exhibited increased beat rate and conduction velocity 24 and 96 hours after treatment. Messenger RNA and protein levels of ion channels were altered, with the most significant changes observed at the 96-hour mark. Upregulation of Cacna1c (Cav1.2), Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1), Kcnj2 (Kir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 (RYR2) and Slc8a1 (NCX) expression and altered properties 96 hours posttreatment. Fibroblast and myofibroblast levels remained unchanged. CONCLUSION: cSBRT modulates the expression of various ion channels, calcium handling proteins, and gap junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed after cSBRT.

Electrophysiological Effects of the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor Dapagliflozin on Human Cardiac Potassium Channels.

The sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin is increasingly used in the treatment of diabetes and heart failure. Dapagliflozin has been associated with reduced incidence of atrial fibrillation (AF) in clinical trials. We hypothesized that the favorable antiarrhythmic outcome of dapagliflozin use may be caused in part by previously unrecognized effects on atrial repolarizing potassium (K+) channels. This study was designed to assess direct pharmacological effects of dapagliflozin on cloned ion channels Kv11.1, Kv1.5, Kv4.3, Kir2.1, K2P2.1, K2P3.1, and K2P17.1, contributing to IKur, Ito, IKr, IK1, and IK2P K+ currents. Human channels coded by KCNH2, KCNA5, KCND3, KCNJ2, KCNK2, KCNK3, and KCNK17 were heterologously expressed in Xenopus laevis oocytes, and currents were recorded using the voltage clamp technique. Dapagliflozin (100 µM) reduced Kv11.1 and Kv1.5 currents, whereas Kir2.1, K2P2.1, and K2P17.1 currents were enhanced. The drug did not significantly affect peak current amplitudes of Kv4.3 or K2P3.1 K+ channels. Biophysical characterization did not reveal significant effects of dapagliflozin on current-voltage relationships of study channels. In conclusion, dapagliflozin exhibits direct functional interactions with human atrial K+ channels underlying IKur, IKr, IK1, and IK2P currents. Substantial activation of K2P2.1 and K2P17.1 currents could contribute to the beneficial antiarrhythmic outcome associated with the drug. Indirect or chronic effects remain to be investigated in vivo.

A porcine large animal model of radiofrequency ablation-induced left bundle branch block.

Background: Electrocardiographic (ECG) features of left bundle branch (LBB) block (LBBB) can be observed in up to 20%-30% of patients suffering from heart failure with reduced ejection fraction. However, predicting which LBBB patients will benefit from cardiac resynchronization therapy (CRT) or conduction system pacing remains challenging. This study aimed to establish a translational model of LBBB to enhance our understanding of its pathophysiology and improve therapeutic approaches. Methods: Fourteen male pigs underwent radiofrequency catheter ablation of the proximal LBB under fluoroscopy and ECG guidance. Comprehensive clinical assessments (12-lead ECG, bloodsampling, echocardiography, electroanatomical mapping) were conducted before LBBB induction, after 7, and 21 days. Three pigs received CRT pacemakers 7 days after LBB ablation to assess resynchronization feasibility. Results: Following proximal LBB ablation, ECGs displayed characteristic LBBB features, including QRS widening, slurring in left lateral leads, and QRS axis changes. QRS duration increased from 64.2 ± 4.2 ms to 86.6 ± 12.1 ms, and R wave peak time in V6 extended from 21.3 ± 3.6 ms to 45.7 ± 12.6 ms. Echocardiography confirmed cardiac electromechanical dyssynchrony, with septal flash appearance, prolonged septal-to-posterior-wall motion delay, and extended ventricular electromechanical delays. Electroanatomical mapping revealed a left ventricular breakthrough site shift and significantly prolonged left ventricular activation times. RF-induced LBBB persisted for 3 weeks. CRT reduced QRS duration to 75.9 ± 8.6 ms, demonstrating successful resynchronization. Conclusion: This porcine model accurately replicates the electrical and electromechanical characteristics of LBBB observed in patients. It provides a practical, cost-effective, and reproducible platform to investigate molecular and translational aspects of cardiac electromechanical dyssynchrony in a controlled and clinically relevant setting.

Prediction of diagnosis and diastolic filling pressure by AI-enhanced cardiac MRI: a modelling study of hospital data.

BACKGROUND: With increasing numbers of patients and novel drugs for distinct causes of systolic and diastolic heart failure, automated assessment of cardiac function is important. We aimed to provide a non-invasive method to predict diagnosis of patients undergoing cardiac MRI (cMRI) and to obtain left ventricular end-diastolic pressure (LVEDP). METHODS: For this modelling study, patients who had undergone cardiac catheterisation at University Hospital Heidelberg (Heidelberg, Germany) between July 15, 2004 and March 16, 2023, were identified, as were individual left ventricular pressure measurements. We used existing patient data from routine cardiac diagnostics. From this initial group, we extracted patients who had been diagnosed with ischaemic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, or amyloidosis, as well as control individuals with no structural phenotype. Data were pseudonymised and only processed within the university hospital's AI infrastructure. We used the data to build different models to predict either demographic (ie, AI-age and AI-sex), diagnostic (ie, AI-coronary artery disease and AI-cardiomyopathy [AI-CMP]), or functional parameters (ie, AI-LVEDP). We randomly divided our datasets via computer into training, validation, and test datasets. AI-CMP was not compared with other models, but was validated in a prospective setting. Benchmarking was also done. FINDINGS: 66 936 patients who had undergone cardiac catheterisation at University Hospital Heidelberg were identified, with more than 183 772 individual left ventricular pressure measurements. We extracted 4390 patients from this initial group, of whom 1131 (25·8%) had been diagnosed with ischaemic cardiomyopathy, 1064 (24·2%) had been diagnosed with dilated cardiomyopathy, 816 (18·6%) had been diagnosed with hypertrophic cardiomyopathy, 202 (4·6%) had been diagnosed with amyloidosis, and 1177 (26·7%) were control individuals with no structural phenotype. The core cohort only included patients with cardiac catherisation and cMRI within 30 days, and emergency cases were excluded. AI-sex was able to predict patient sex with areas under the receiver operating characteristic curves (AUCs) of 0·78 (95% CI 0·77-0·78) and AI-age was able to predict patient age with a mean absolute error of 7·86 years (7·77-7·95), with a Pearson correlation of 0·57 (95% CI 0·56-0·57). The AUCs for the classification tasks ranged between 0·82 (95% CI 0·79-0·84) for ischaemic cardiomyopathy and 0·92 (0·91-0·94) for hypertrophic cardiomyopathy. INTERPRETATION: Our AI models could be easily integrated into clinical practice and provide added value to the information content of cMRI, allowing for disease classification and prediction of diastolic function. FUNDING: Informatics for Life initiative of the Klaus-Tschira Foundation, German Center for Cardiovascular Research, eCardiology section of the German Cardiac Society, and AI Health Innovation Cluster Heidelberg.

Increase of Cardiac Autoantibodies Against Beta-2-adrenergic Receptor During Acute Cellular Heart Transplant Rejection.

BACKGROUND: Acute cellular rejection (ACR) in heart transplant (HTx) recipients may be accompanied by cardiac cell damage with subsequent exposure to cardiac autoantigens and the production of cardiac autoantibodies (aABs). This study aimed to evaluate a peptide array screening approach for cardiac aABs in HTx recipients during ACR (ACR-HTx). METHODS: In this retrospective single-center observational study, sera from 37 HTx recipients, as well as age and sex-matched healthy subjects were screened for a total of 130 cardiac aABs of partially overlapping peptide sequences directed against structural proteins using a peptide array approach. RESULTS: In ACR-HTx, troponin I (TnI) serum levels were found to be elevated. Here, we could identify aABs against beta-2-adrenergic receptor (ß-2AR: EAINCYANETCCDFFTNQAY) to be upregulated in ACR-HTx (intensities: 0.80 versus 1.31, P = 0.0413). Likewise, patients positive for ß-2AR aABs showed higher TnI serum levels during ACR compared with aAB negative patients (10.0 versus 30.0 ng/L, P = 0.0375). Surprisingly, aABs against a sequence of troponin I (TnI: QKIFDLRGKFKRPTLRRV) were found to be downregulated in ACR-HTx (intensities: 3.49 versus 1.13, P = 0.0025). A comparison in healthy subjects showed the same TnI sequence to be upregulated in non-ACR-HTx (intensities: 2.19 versus 3.49, P = 0.0205), whereas the majority of aABs were suppressed in non-ACR-HTx. CONCLUSIONS: Our study served as a feasibility analysis for a peptide array screening approach in HTx recipients during ACR and identified 2 different regulated aABs in ACR-HTx. Hence, further multicenter studies are needed to evaluate the prognostic implications of aAB testing and diagnostic or therapeutic consequences.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.