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Abstract Introduction Atrial fibrillation (AF) and heart failure (HF) often coexist due to the common elements of the pathomechanism they share. The potential significance of the order these entities present in the same patient is ill-defined. Herein, we report our results from a nationwide database on the occurrence of various sequences AF and HF may present, the time delays between the two conditions and all-cause mortality associated with different scenarios. Methods Patients diagnosed with both AF and HF between 2015 and 2021 were enrolled from the Hungarian National Health Insurance Fund (NHIF) database. The order the two entities followed each other, and the time delay in between were registered. Median survival rates were calculated in AF → HF; HF → AF and simultaneous scenarios. Results A total of 109,075 patients were enrolled: 29,937 with AF → HF, 38,171 with HF → AF, and 40,967 diagnosed simultaneously. Time delays between AF → HF and HF → AF were 6 and 10 months, respectively. The median survival was 46 months in the AF → HF, 38 months in the HF → AF, and 21 months in the simultaneous group. Patients with HF → AF, and with simultaneous presentations had 5% and 16% greater mortality risk as compared to the AF → HF sequence, with hazard ratios (95% confidence intervals) of 0.95 (0.93–0.97) and 0.84 (0.82–0.85), respectively (P

Abstract Despite improvements over recent years, morbidity and mortality associated with heart failure (HF) are higher in countries in the Central and Eastern Europe and Baltic region than in Western Europe. With the goal of improving the standard of HF care and patient outcomes in the Central and Eastern Europe and Baltic region, this review aimed to identify the main barriers to optimal HF care and potential areas for improvement. This information was used to suggest methods to improve HF management and decrease the burden of HF in the region that can be implemented at the national and regional levels. We performed a literature search to collect information about HF epidemiology in 11 countries in the region (Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, and Slovenia). The prevalence of HF in the region was 1.6–4.7%, and incidence was 3.1–6.0 per 1000 person‐years. Owing to the scarcity of published data on HF management in these countries, we also collected insights on local HF care and management practices via two surveys of 11 HF experts representing the 11 countries. Based on the combined results of the literature review and surveys, we created national HF care and management profiles for each country and developed a common patient pathway for HF for the region. We identified five main barriers to optimal HF care: (i) lack of epidemiological data, (ii) low awareness of HF, (iii) lack of national HF strategies, (iv) infrastructure and system gaps, and (v) poor access to novel HF treatments. To overcome these barriers, we propose the following routes to improvement: (i) establish regional and national prospective HF registries for the systematic collection of epidemiological data; (ii) establish education campaigns for the public, patients, caregivers, and healthcare professionals; (iii) establish formal HF strategies to set clear and measurable policy goals and support budget planning; (iv) improve access to quality‐of‐care centres, multidisciplinary care teams, diagnostic tests, and telemedicine/telemonitoring; and (v) establish national treatment monitoring programmes to develop policies that ensure that adequate proportions of healthcare budgets are reserved for novel therapies. These routes to improvement represent a first step towards improving outcomes in patients with HF in the Central and Eastern Europe and Baltic region by decreasing disparities in HF care within the region and between the region and Western Europe.

Abstract Mitral stenosis (MS) is a complex valvular pathology with significant clinical burden even today. Its effect on the right heart is often overlooked, despite it playing a considerable part in the symptomatic status. We enrolled 39 mitral valve stenosis patients and 39 age- and gender-matched healthy controls. They underwent conventional, speckle-tracking and 3D echocardiographic examinations. The 3D data was analyzed using the ReVISION software to calculate RV functional parameters. In the MS group, 3D RV ejection fraction (EF) (49 ± 7% vs. 61 ± 4%; p

Background Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device‐detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device‐detected AF but with no ECG‐documented AF is unclear. Methods and Results This prespecified analysis of the NOAH‐AFNET 6 (Non‐Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device‐detected AF with and without a prior stroke or TIA in the randomized, double‐blind, double‐dummy NOAH‐AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device‐detected AF randomized in the NOAH‐AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time‐to‐event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient‐year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient‐year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient‐year]; no anticoagulation: 6 out of 131 [2.3% per patient‐year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). Conclusions Anticoagulation appears to have ambiguous effects in patients with device‐detected AF and a prior stroke or TIA in this hypothesis‐generating analysis of the NOAH‐AFNET 6 in the absence of ECG‐documented AF, partially due to a low rate of stroke without anticoagulation.

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain low, and early prognostication is challenging. While numerous intensive care unit scoring systems exist, their utility in the early hours following hospital admission, specifically in the targeted temperature management (TTM) population, is questionable. Our aim was to create a score system that may accurately estimate outcome within the first 12 h after admission in patients receiving TTM. Methods: We analyzed data from 103 OHCA patients who subsequently underwent TTM between 2016 and 2022. Patient demographic data, prehospital characteristics, clinical and laboratory parameters were already available in the first 12 h after admission were collected. Following a bootstrap-based predictor selection, we constructed a nonlinear logistic regression model. Internal validation was performed using bootstrap resampling. Discrimination was described using the c-statistic, whereas calibration was characterized by the intercept and slope. Results: According to the Akaike Information Criterion (AIC) heart rate (AIC = 9.24, p = 0.0013), age (AIC = 4.39, p = 0.0115), pH (AIC = 3.68, p = 0.0171), initial rhythm (AIC = 4.76, p = 0.0093) and right ventricular end-diastolic diameter (AIC = 2.49, p = 0.0342) were associated with 30-day mortality and were used to build our predictive model and nomogram. The area under the receiver-operating characteristics curve for the model was 0.84. The model achieved a C-statistic of 0.7974, with internally validated acceptable calibration (intercept: −0.0190, slope: 0.7772) and low error rates (mean absolute error: 0.040). Conclusion: The model we have developed may be suitable for early risk assessment of patients receiving TTM as part of primary post-resuscitation care. The calculator needed for scoring can be accessed at the following link: https://www.rapidscore.eu/.

Background: Comirnaty, Pfizer-BioNTech's polyethylene-glycol (PEG)-containing Covid-19 vaccine, can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis in a small fraction of immunized people. A causal role of anti-PEG antibodies (Abs) has been proposed, but causality has not yet proven in an animal model. The aim of this study was to provide such evidence using pigs immunized against PEG, which displayed very high levels of anti-PEG antibodies (Abs). We also aimed to find evidence for a role of complement activation and thromboxane A2 release in blood to explore the mechanism of anaphylaxis. Methods: Pigs (n = 6) were immunized with 0.1 mg/kg PEGylated liposome (Doxebo) i.v., and the rise of anti-PEG IgG and IgM were measured in serial blood samples with ELISA. After ∼2–3 weeks the animals were injected i.v. with 1/3 human dose of the PEGylated mRNA vaccine, Comirnaty, and the hemodynamic (PAP, SAP) cardiopulmonary (HR, EtCO2,), hematological (WBC, granulocyte, lymphocyte and platelet counts) parameters and blood immune mediators (anti-PEG IgM and IgG antibodies, thromboxane B2, C3a) were measured as endpoints of HSRs (anaphylaxis). Results: The level of anti-PEG IgM and IgG rose 5–10-thousand-fold in all of 6 pigs immunized with Doxebo by day 6, after which time all animals developed anaphylactic shock to i.v. injection of 1/3 human dose of Comirnaty. The reaction, starting within 1 min involved maximal pulmonary hypertension and decreased systemic pulse pressure amplitude, tachycardia, granulo- and thrombocytopenia, and skin reactions (flushing or rash). These physiological changes or their absence were paralleled by C3a and TXB2 rises in blood. Conclusions: Consistent with previous studies, these data show a causal role of anti-PEG Abs in the anaphylaxis to Comirnaty, which involves complement activation, and, hence, it represents C activation-related pseudo-anaphylaxis. The setup provides the first large-animal model for mRNA-vaccine-induced anaphylaxis in humans.

Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1—but not SGLT2—activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial. In this prespecified meta-analysis, we included 6 randomized, placebo-controlled cardiovascular outcome trials of SGLT2 inhibitors assessing MACE in 57,553 patients with T2DM. Mixed-effects meta-regression revealed that pharmacological selectivity of SGLT2 inhibitors (either as continuous or dichotomized variable) had no significant impact on most outcomes. However, lower SGLT2 selectivity correlated with significantly lower risk of stroke (pseudo-R2 = 78%; p = 0.011). Indeed, dual SGLT1/2 inhibitors significantly reduced the risk of stroke (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.64–0.94), unlike selective agents (p for interaction = 0.018). The risk of diabetic ketoacidosis and genital infections was higher in both pharmacological groups versus placebo. However, hypotension occurred more often with non-selective SGLT2 inhibitors (odds ratio [OR], 1.87; 95% CI, 1.20–2.92) compared with selective agents (p for interaction = 0.044). In conclusion, dual SGLT1/2 inhibition reduces stroke in high-risk T2DM patients but has limited additional effect on other clinical outcomes.

Background: Basic life support (BLS) skills are crucial not only for healthcare workers but for all lay people as well. Timely recognition of out-of-hospital cardiac arrest (OHCA) and the initiation of BLS by bystanders before the arrival of healthcare personnel may improve survival. There are several methods of spreading BLS skills and improve BLS skill retention among lay people. One of these methods can be the education of adolescent school children. The introduction of mandatory BLS education in schools was very effective in some European countries to increase the rate of bystander BLS. Methods/design: The current study aims to investigate the efficacy of a BLS training and BLS curriculum among high school children in Hungary. Moreover, the investigators would like to optimise factors influencing skill retention in this first responder group and aim to compare two types of teaching methods: feedback given by the instructor or software-based feedback on the efficacy of chest compressions during the course. This study will be an interventional, assessor blinded, individually randomised parallel group trial recruiting 360 students. BLS skill retention will be assessed at the end of the course, two months after the training and six months after training. Discussion: The current study will increase our knowledge on the methods educating BLS among high school children. The results will help us to create an effective BLS curriculum at schools.Trial registration: ClinicalTrials.gov: NCT06016153. Prospectively registered on 08/2023.

Introduction and aimsVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients.MethodsThe MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48–72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score.ConclusionsThe MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

ObjectivesCardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome.DesignBIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment.SettingTertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians.ParticipantsPatients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction >35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women).InterventionsPatients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring.Main outcome measuresMACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes.Results790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P

Age-related disorders are closely linked to the accumulation of senescent cells. The senescence-associated secretory phenotype (SASP) sustains and progresses chronic inflammation, which is involved in cellular and tissue dysfunction. SASP-related growth and differentiation factor-15 (GDF-15) is an immunoregulatory cytokine that is coupled to aging and thus may have a regulatory role in the development and maintenance of atherosclerosis, a major cause of cardiovascular disease (CVD). Although the effects of GDF-15 are tissue-specific and dependent on microenvironmental changes such as inflammation, available data suggest that GDF-15 has a significant role in CVD. Thus, GDF-15 is a promising biomarker and potential therapeutic target for atherosclerotic CVD.

Abstract Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228–0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854–0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980–0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification ).

Background: Recurrences due to discontinuity in ablation lines are substantial after pulmonary vein isolation (PVI) with radiofrequency ablation for atrial fibrillation. Data are scarce regarding the durability predictors for very high-power short-duration (vHPSD, 90 W/4 s) ablation. Methods: A total of 20 patients were enrolled, who underwent 90 W PVI and a mandatory remapping procedure at 3 months. First-pass isolation (FPI) gaps, and acute pulmonary vein reconnection (PVR) sites were identified at the index procedure; and chronic PVR sites were identified at the repeated procedure. We analyzed parameters of ablation points (n = 1357), and evaluated their roles in predicting a composite endpoint of FPI gaps, acute and chronic PVR. Results: In total, 45 initial ablation points corresponding to gaps in the ablation lines were analyzed. Parameters associated with gaps were interlesion distance (ILD), baseline generator impedance, mean current, total charge, and loss of catheter–tissue contact. The optimal ILD cut-off for predicting gaps was 3.5 mm anteriorly, and 4 mm posteriorly. Conclusions: Biophysical characteristics dependent on generator impedance could affect the efficacy of vHPSD PVI. The use of smaller ILDs is required for effective and durable PVI with vHPSD compared to the consensus targets with lower power ablation, and lower ILDs for anterior applications seem necessary compared to posterior points.

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: −30.1% iNO, −22.1% SIN-1A-5, −31.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability.

IntroductionThe genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF.MethodsWe included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered “red flags”.ResultsOf the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found.DiscussionThe large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.

BackgroundCardiac rotational parameters in primary symptomatic left ventricular noncompaction (LVNC) with preserved left ventricular ejection fraction (LVEF) are not well understood. We aimed to analyze cardiac rotation measured with cardiac magnetic resonance feature-tracking (CMR-FT) and speckle-tracking echocardiography (Echo-ST) in LVNC morphology subjects with preserved LVEF and different genotypes and healthy controls.MethodsOur retrospective study included 54 LVNC subjects with preserved LVEF and 54 control individuals. We evaluated functional and rotational parameters with CMR in the total study population and with echocardiography in 39 LVNC and 40 C individuals. All LVNC subjects were genotyped with a 174-gene next-generation sequencing panel and grouped into the subgroups: benign (B), variant of uncertain significance (VUS), and pathogenic (P).ResultsIn comparison with controls, LVNC subjects had reduced apical rotational degree (p = 0.004) and one-third had negative apical rotation. While the degree of apical rotation was comparable between the three genetic subgroups, they differed significantly in the direction of apical rotation (pConclusionWhile measuring cardiac rotation using both CMR-FT and Echo-ST methods, subclinical mechanical differences were identified in subjects with LVNC phenotype and preserved LVEF, especially in cases with genetic involvement.

Abstract Although systolic function characteristically shows gradual impairment in pressure overload (PO)-evoked left ventricular (LV) hypertrophy (LVH), rapid progression to congestive heart failure (HF) occurs in distinct cases. The molecular mechanisms for the differences in maladaptation are unknown. Here, we examined microRNA (miRNA) expression and miRNA-driven posttranscriptional gene regulation in the two forms of PO-induced LVH (with/without systolic HF). PO was induced by aortic banding (AB) in male Sprague–Dawley rats. Sham-operated animals were controls. The majority of AB animals demonstrated concentric LVH and slightly decreased systolic function (termed as ABLVH). In contrast, in some AB rats severely reduced ejection fraction, LV dilatation and increased lung weight-to-tibial length ratio was noted (referred to as ABHF). Global LV miRNA sequencing revealed fifty differentially regulated miRNAs in ABHF compared to ABLVH. Network theoretical miRNA-target analysis predicted more than three thousand genes with miRNA-driven dysregulation between the two groups. Seventeen genes with high node strength value were selected for target validation, of which five (Fmr1, Zfpm2, Wasl, Ets1, Atg16l1) showed decreased mRNA expression in ABHF by PCR. PO-evoked systolic HF is associated with unique miRNA alterations, which negatively regulate the mRNA expression of Fmr1, Zfmp2, Wasl, Ets1 and Atg16l1.

Abstract This study assessed the experiences of elite aquatic athletes with coronavirus disease 2019 (COVID-19) during the first World Championship conducted without social distancing and an isolation “bubble”. An online questionnaire was completed by 812 athletes (22.7 ± 5.9 years, 467 females) to provide data on demographics, sports activity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, symptoms, reinfection, vaccination status, and psychological aspects. The answers revealed that 49.4% of athletes had experienced SARS-CoV-2 infection. The infection rates varied significantly across different aquatic sports, with open water swimmers having the lowest (28%) and water polo players (67%) and artistic swimmers (61%) having the highest infection rates (p

Diastolic dysfunction (DD) is a prevalent and clinically significant complication after heart transplantation (HTX). We aimed to characterize the diastolic function of HTX recipients with both short-term and long-term follow-ups by applying left atrial (LA) deformation analysis. We consecutively enrolled and followed up with 33 HTX patients. Three assessments were performed one month, 3–5 months, and 3–5 years after surgery. Beyond conventional echocardiographic measurements, apical four-chamber views optimized for speckle tracking analysis were acquired and post-processed by dedicated software solutions (TomTec AutoStrain LA and LV). Left atrial phasic functions were characterized by reservoir, conduit, and contraction strains. We categorized diastolic function according to current guidelines (normal diastolic function, indeterminate, DD). At the first assessment, nine (27%) patients were in the DD category, and eleven (33%) were indeterminate. At the second assessment, only one patient (3%) remained in the DD category and six (18%) were indeterminate. At the third assessment, 100% of patients were categorized as having normal diastolic function. LA reservoir strain gradually increased over time. LA contraction strain significantly improved from the second to the third assessment. We found a correlation between the LA reservoir strain and NT-proBNP (r = 0.40, p < 0.05). DD is prevalent immediately after HTX but rare until the end of the first postoperative quarter. Speckle tracking analysis enables the characterization of LA phasic functions that may reflect both short- and long-term changes in diastolic function and correlate with NT-proBNP.

Background: Frailty has been proven to be associated with mortality after orthotopic heart transplantation (OHT). The aim of our study was to determine the impact of frailty on mortality in the current era using pretransplant mechanical cardiac support (MCS). Methods: We retrospectively calculated the frailty scores of 471 patients undergoing OHT in a single institution between January 2012 and August 2022. The outcome was all-cause mortality. Results: The median survival time was 1987 days (IQR: 1487 days) for all patients. In total, 266 (56.5%) patients were categorized as nonfrail, 179 (38.0%) as prefrail, and 26 (5.5%) as frail. The survival rates were 0.73, 0.54, and 0.28 for nonfrail, prefrail, and frail patients, respectively. The frailty score was associated with mortality [HR: 1.34 (95% CI: 1.22–1.47, p < 0.001)]. Among the components of the frailty score, age above 50 years, creatinine ≥ 3.0 mg/dL or prior dialysis, and hospitalization before OHT were independently associated with mortality. Continuous-flow left ventricular assist devices (CF-LVAD) were associated with an increased risk for all-cause mortality [AHR: 1.80 (95% CI: 1.01–3.24, p = 0.047)]. Conclusions: The components of the frailty score were not equally associated with mortality. Frailty and pretransplant MCS should be included in the risk estimation.

Abstract Aims Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non‐absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results PRIORITIZE‐HF was an international, multicentre, parallel‐group, randomized, double‐blind, placebo‐controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID‐19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions PRIORITIZE‐HF was terminated prematurely due to COVID‐19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium‐reducing agent SZC compared with placebo.

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography.The aspects of right ventricular volumes and function investigated with 3D echocardiography in a large cohort of left ventricular noncompaction morphology (LVNC) population remains unclear.The objective of our research was to study the left (LV) and right (RV) ventricular parameters using 3D echocardiography and analyze the clinical features of a LVNC population with preserved LV ejection fraction (EF > 50 %) in comparison with healthy controls (HC).We selected 41 LVNC subjects with preserved LV function (EF: 52.91 ± 3 %, male n = 26) and without any comorbidities and compared them with an age and sex-matched HC. Three dimensional endocardial contours were evaluated to determine the following LV and RV parameters: end-diastolic (EDV) and end-systolic (ESV) volumes, stroke volume, EF, LV global longitudinal and circumferential strain and RV septal and free wall longitudinal strain.Regarding the clinical characteristics, the family involvement had a notable proportion, accounting for 51%. The EF and strain values of the LVNC population were significantly decreased in both RV and LV compared to HC. Although the LV volumes of the LVNC group were significantly elevated, the RV volumetric parameters did not differ significantly compared to controls. We found significant correlations between LV and RV volumetric and functional parameters and linear regression models showed that LV EDV and LV ESV determined the RV volumetric values.While the alteration and relationship of the RV parameters may represent the potential of biventricular involvement, clinical characteristics of the LVNC group underlines the necessity of monitoring this population, even with preserved EF.

Abstract Background Heart transplant (HTX) recipients are prone to develop complications after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Vaccination is often ineffective due to weaker immunogenicity. In this high‐volume single‐center study, we aimed to determine factors influencing seroconversion after vaccination and predictors of severe SARS‐CoV‐2 infection. Methods Two hundred twenty‐nine HTX recipients were enrolled. Type of the first two vaccine doses included messenger RNA (mRNA), vector, and inactivated vaccines. We carried out analyses on seroconversion after the second and third doses of vaccination and on severity of infection. Antispike protein SARS‐CoV‐2 immunoglobulin G (IgG) was measured after the second and third vaccines and serostatus was defined. Effect of the first two vaccine doses was studied on patients who did not suffer SARS‐CoV‐2 infection before antibody measurement (n = 175). The effectivity of the third vaccine was evaluated among seronegative recipients after the second vaccine (n = 53). Predictors for severe infection defined as pneumonia, hospitalization or death were assessed in all patients who contracted SARS‐CoV‐2 infection (n = 92). Results 62% of the recipients became seropositive after the second vaccination. Longer time between HTX and vaccination (odds ratio [OR]: 2.35) and mRNA vaccine (OR: 4.83) were predictors of seroconversion. 58% of the nonresponsive patients became seropositive after receiving the third vaccine. Male sex increased the chance of IgG production after the third dose (OR: 5.65). Clinical course of SARS‐CoV‐2 infection was severe in 32%. Of all parameters assessed, only seropositivity before infection was proven to have a protective effect against severe infection (OR: 0.11). Conclusions We found that longer time since HTX, mRNA vaccine type, and male sex promoted seroconversion after SARS‐CoV‐2 vaccination in HTX recipients. Seropositivity—but not the number of vaccine doses—seemed to be protective against severe SARS‐CoV‐2 infection. Screening of HTX patients for anti‐SARS‐COV‐2 antibodies may help to identify patients at risk for severe infection.

Cardiogenic shock (CS) in acute coronary syndrome (ACS) is a critical disease with high mortality rates requiring complex treatment to maximize patient survival chances. Emergent coronary revascularization along with circulatory support are keys to saving lives. Mechanical circulatory support may be instigated in severe, yet still reversible instances. Of these, the peripheral veno-arterial extracorporeal membrane oxygenator (pVA-ECMO) is the most widely used system for both circulatory and respiratory support. The aim of our work is to provide a review of our current understanding of the pVA-ECMO when used in the catheterization laboratory in a CS ACS setting. We detail the workings of a Shock Team: pVA-ECMO specifics, circumstances, and timing of implantations and discuss possible complications. We place emphasis on how to select the appropriate patients for potential pVA-ECMO support and what characteristics and parameters need to be assessed. A detailed, stepwise implantation algorithm indicating crucial steps is also featured for practitioners in the catheter laboratory. To provide an overall aspect of pVA-ECMO use in CS ACS we further gave pointers including relevant human resource, infrastructure, and consumables management to build an effective Shock Team to treat CS ACS via the pVA-ECMO method.

Abstract Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1β targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional—and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH. In conclusion, IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.

Background: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is predominantly attributed to pulmonary vein reconnection (PVR). Predictors of AF recurrence have been widely studied; however, data are scarce on procedural parameters that predict chronic PVR. We aimed to study PVR rates and predictors of PVR. Methods: We retrospectively included 100 patients who underwent repeated ablation due to AF recurrence after initial PVI with the CARTO system. PVR was determined during the repeated procedure by electrophysiological evaluation, and initial procedural characteristics predicting PVR were studied, including adherence to the CLOSE protocol, use of high power, first-pass isolation (FPI), and baseline generator impedance (BGI). Results: Thirty-eight patients underwent initial CLOSE-guided PVI, and sixty-two underwent initial non-CLOSE PVI. A repeat procedure was performed 23 ± 16 months after the initial procedure. In total, PVR was found in 192 of 373 PVs (51.5%), and all PVs were isolated in 17/100 (17%) patients. Factors associated with all PVs being isolated were adherence to the CLOSE protocol, a higher power setting, the presence of bilateral FPI, and lower BGI (88% vs. 28%, p < 0.0001; 37.5 W vs. 30 W, p = 0.0276; 88.2% vs. 40.4%, p = 0.0007; and 127.6 Ω vs. 136.6 Ω, p = 0.0027, respectively). In initial procedures with adherence to the CLOSE protocol, the FPI rate was significantly higher (73.7% vs. 25%, p < 0.0001), while there were no significant differences in terms of procedure time and left atrial dwell time (81 vs. 85 min, p = 0.83; and 60 vs. 58 min, p = 0.08, respectively). BGI ≥ 130 Ω (AUC = 0.7403, sensitivity: 77.1%, specificity: 68.8%, p = 0.0032) was associated with a significantly higher probability of PVR (OR = 6.757; p < 0.0001). In multivariable analysis, independent predictors for PVR were non-adherence to the CLOSE protocol and BGI ≥ 130 Ω. Conclusions: Our findings indicate that adherence to the CLOSE protocol and baseline generator impedance < 130 Ω during AF ablation are independent predictors of PVI durability.

Background: End-stage heart failure (ESHF) leads to hypoperfusion and edema formation throughout the body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Purpose: In this study, our aim was to explore the relationship between the clinical outcomes of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at heart transplantation after opening the pericardial sac. Materials and methods: The clinical data and the interleukin, adipokine, and lipoprotein levels in the pericardial fluid of twenty HTX recipients were investigated. Outcome variables included primer graft dysfunction (PGD), the need for post-transplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥2R rejection, and mortality. Recipient risk scores were also investigated. Results: Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 (IQR: 5.55–6.62) versus 7.54 (IQR = 6.71–10.44); p = 0.029). Higher ApoCII levels (median: 14.91 (IQR: 11.55–21.30) versus 10.31 (IQR = 10.02–13.07); p = 0.042) and ApoCIII levels (median: 60.32 (IQR: 43.00–81.66) versus 22.84 (IQR = 15.84–33.39); p = 0.005) were found in patients (n = 5) who died in the first 5 years after HTX. In patients who exhibited rejection (n = 4) in the first month after transplantation, the levels of adiponectin (median: 74.48 (IQR: 35.51–131.70) versus 29.96 (IQR: 19.86–42.28); p = 0.039), ApoCII (median: 20.11 (IQR: 13.06–23.54) versus 10.32 (IQR: 10.02–12.84); p = 0.007), and ApoCIII (median: 70.97 (IQR: 34.72–82.22) versus 26.33 (IQR: 17.18–40.17); p = 0.029) were higher than in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 (IQR: 3.49–4.46) versus 4.69 (IQR: 4.23–5.77); p = 0.022) were lower in patients with rejection than in patients who did not develop rejection. Conclusion: Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecasting of early and late complications.

Background: Safety, efficacy, and patient comfort are the expectations during pulmonary vein isolation (PVI). We aimed to validate the combined advantages of pre- and periprocedural anticoagulation with non-vitamin K anticoagulants (NOACs) and rigorous left atrial appendage thrombus (LAAT) exclusion with computed tomography (CT). Methods: This study included a population of consecutive patients, between March 2018 and June 2020, who underwent cardiac CT within 24 h before PVI to guide the ablation and rule out LAAT. NOAC was omitted 24 h before the ablation. Results: A total of 187 patients (63% male) underwent CT before PVI. None of the patients experienced stroke during or after the procedure. The complication rate was low, with no thromboembolic events and 2.1% of patients experiencing a major bleeding event. Conclusions: Omitting NOAC 24 h before the ablation might be safe if combined with left atrial thrombus exclusion with computed tomography.

BackgroundThe right ventricle (RV) has complex geometry and function, with motion along three separate axes—longitudinal, radial, and anteroposterior. Quantitative assessment of RV function by two-dimension echocardiography (2DE) has been limited as a consequence of this complexity, whereas newer three dimensional (3D) analysis offers the potential for more comprehensive assessment of the contributors to RV function. The aims of this study were to quantify the longitudinal, radial and anteroposterior components of global RV function using 3D echocardiography in a cohort of healthy children and to examine maturational changes in these parameters.MethodsThree-dimensional contours of the RV were generated from a cohort of healthy pediatric patients with structurally normal hearts at two centers. Traditional 2D and 3D echo characteristics were recorded. Using offline analysis of 3D datasets, RV motion was decomposed into three components, and ejection fractions (EF) were calculated (longitudinal-LEF; radial-REF; and anteroposterior-AEF). The individual decomposed EF values were indexed against the global RVEF. Strain values were calculated as well.ResultsData from 166 subjects were included in the analysis; median age was 13.5 years (range 0 to 17.4 years). Overall, AEF was greater than REF and LEF (29.2 ± 6.2% vs. 25.1 ± 7.2% and 25.7 ± 6.0%, respectively; p

PurposeOur purpose was to compare the procedural characteristics, success rate, and complication rate of the conventional fluoroscopic (CF) and the zero-fluoroscopic (ZF) approach in patients undergoing catheter ablation of AVNRT or typical atrial flutter (Aflu).Methods186 consecutive patients with an indication for AVNRT or Aflu ablation were enrolled. Based on the operator's preference, the patients were assigned to either CF or ZF group. In the ZF group EnSite NavX, Carto3, or Rhythmia EAMS were used for catheter guidance.ResultsThe median age was 56 (IQR = 42−68) years, 144 patients had AVNRT, and 42 had Aflu ablation. CF approach was chosen in 123 cases, while ZF in 63 cases. ZF approach was used more often in case of AVNRT patients [56 (39%) vs. 7 (17%), p = 0.006] and in the case of female patients [43 (68%) vs. 20 (32%), p = 0.008]. Acute procedural success was obtained in all cases. There was no difference in the complication rate (1 vs. 1, p > 0.99) between the two groups. No difference was found regarding the procedure time between the CF and ZF groups [CF: 55 (46–60) min, ZF 60 (47–65) min; p = 0.487] or in the procedure time for the different EAMS [EnSite NavX: 58 (50–63) min, Carto3: 60 (44.5–66.3) min, Rhythmia: 55 (35–69) min; p = 0.887]. A similar success rate was seen at the 3-month follow-up in the two groups [41 (100%) vs. 96 (97%); p = 0.55].DiscussionThe ZF approach demonstrated non-inferiority in safety and efficacy compared with CF for the AVNRT and Aflu ablations.

Background Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer.Methods In this case–control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI).Results The patients had a median age of 66 years (IQR: 58–69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression.Conclusions ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment.Trial registration number NCT04430712.

IntroductionStructural and functional heart abnormalities can be examined non-invasively with cardiac magnetic resonance imaging (CMR). Thanks to the development of MR devices, diagnostic scans can capture more and more relevant information about possible heart diseases. T1 and T2 mapping are such novel technology, providing tissue specific information even without the administration of contrast material. Artificial intelligence solutions based on deep learning have demonstrated state-of-the-art results in many application areas, including medical imaging. More specifically, automated tools applied at cine sequences have revolutionized volumetric CMR reporting in the past five years. Applying deep learning models to T1 and T2 mapping images can similarly improve the efficiency of post-processing pipelines and consequently facilitate diagnostic processes.MethodsIn this paper, we introduce a deep learning model for myocardium segmentation trained on over 7,000 raw CMR images from 262 subjects of heterogeneous disease etiology. The data were labeled by three experts. As part of the evaluation, Dice score and Hausdorff distance among experts is calculated, and the expert consensus is compared with the model’s predictions.ResultsOur deep learning method achieves 86% mean Dice score, while contours provided by three experts on the same data show 90% mean Dice score. The method’s accuracy is consistent across epicardial and endocardial contours, and on basal, midventricular slices, with only 5% lower results on apical slices, which are often challenging even for experts.ConclusionsWe trained and evaluated a deep learning based segmentation model on 262 heterogeneous CMR cases. Applying deep neural networks to T1 and T2 mapping could similarly improve diagnostic practices. Using the fine details of T1 and T2 mapping images and high-quality labels, the objective of this research is to approach human segmentation accuracy with deep learning.

Abstract Background Refractory cardiogenic shock is still a major clinical challenge with high mortality rates, although several devices can be used to conquer this event. These devices have different advantages and disadvantages originating from their insertion or cannulation method, therefore many complications can occur during their use. The aim of our study was to develop and create prototypes of a novel minimal invasively insertable, transapical cannula for surgical ventricular assist devices, which uniquely incorporates the inflow and outflow routes for the blood of the patient in itself, therefore it enables the use for only one cannula for patients in cardiogenic shock. Methods To define the available space for the planned cannula in the left ventricle and ascending aorta, we analyzed computed tomography scans of 24 heart failure patients, who were indicated to left ventricular assist device therapy. Parallel to these measurements, hydrodynamical calculations were performed to determine the sizes of the cannulas, which were necessary to provide effective cardiac output. Results After the designing steps, we produced prototypes of double-lumened, tube-in-tube apically insertable devices for three different patient groups, which included a separated venous and an arterial part using 3D modelling and printing technology. All the created cannulas are able to provide 5 l/min circulatory support. Conclusion As a result of our research we created a sizing method based on the specific analysis of computed tomography pictures of end stage heart failure patients and a cannula concept, which can provide effective antegrade flow for patients in cardiogenic shock. We believe the improved version of our tool could have a significant therapeutic role in the future after further development based on animal and in vivo tests.

Abstract Aims Inflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation‐related histological and molecular alterations in HF‐associated AF. The objective of our study was to investigate inflammatory pathways and fibrosis in end‐stage HF‐associated AF. Methods and results Left atrial samples of 24 male patients with end stage ischemic HF undergoing heart transplantation were analysed. Twelve patients suffered from sustained AF while the others had no documented AF. The expression of inflammasome sensors and their downstream signalling were investigated by Western blot. No differences were observed in the expression of inflammasome sensors between the two groups, while cleaved caspase‐1 increased tendentiously in the AF group (P = 0.051). Cleaved caspase‐1 also showed significant correlation with the expression of interleukin‐1β and its cleaved form in the total population and in the AF group (P

IntroductionLeft atrial appendage (LAA) thrombus is the most common source of embolization in atrial fibrillation (AF). Transesophageal echocardiography (TEE) is the gold standard method for LAA thrombus exclusion. Our pilot study aimed to compare the efficacy of a new non-contrast-enhanced cardiac magnetic resonance (CMR) sequence (BOOST) with TEE for the detection of LAA thrombus and to evaluate the usefulness of BOOST images for planning radiofrequency catheter ablation (RFCA) compared with left atrial (LA) contrast-enhanced computed tomography (CT). We also attempted to assess the patients' subjective experiences with TEE and CMR.MethodsPatients with AF undergoing either electrical cardioversion or RFCA were enrolled. Participants underwent pre-procedural TEE and CMR scans to evaluate LAA thrombus status and pulmonary vein anatomy. Patient experiences with TEE and CMR were assessed using a questionnaire developed by our team. Some patients scheduled for RFCA also had pre-procedural LA contrast-enhanced CT. In such cases, the operating physician was asked to subjectively define the quality of the CT and CMR scan on a scale of 1–10 (1 = worst, 10 = best) and comment on CMR's usefulness in RFCA planning.ResultsSeventy-one patients were enrolled. In 94.4%, both TEE and CMR excluded, and in 1 patient, both modalities reported the presence of LAA thrombus. In 1 patient, TEE was inconclusive, but CMR excluded LAA thrombus. In 2 patients, CMR could not exclude the presence of thrombus, but in 1 of those cases, TEE was also indecisive. During TEE, 67%, during CMR, only 1.9% of patients reported pain (p

Drug-eluting stent in-stent restenosis (DES-ISR) remains one of the important assignments to be resolved in interventional cardiology, as it is present in 5%–10% of total percutaneous coronary intervention cases. Drug-coated balloon (DCB) utilization is promising, as it comes with long-term protection from recurrent restenosis in optimal conditions without the hazard of higher risk for stent thrombosis and in-stent restenosis. We aim to reduce the need for recurrent revascularization in DES-ISR, specifying the population in which the DCB therapy should be used. In this meta-analysis, the results of studies containing data on the time frame between drug-eluting stent implantation and the clinical presentation of in-stent restenosis and concomitant drug-coated balloon treatment were summarized. A systematic search was performed in Medline, Central, Web of Science, Scopus and Embase databases on November 11th, 2021. The QUIPS tool was used to assess the risk of bias in the included studies. The occurrence of a major cardiac adverse events (MACE) composite endpoint, containing target lesion revascularization (TLR), myocardial infarction, and cardiac death, and each of these separately, was assessed at 12 months after the balloon treatment. Random effects meta-analysis models were used for statistical analysis. Data of 882 patients from four studies were analyzed. Across the included studies, a 1.68 OR (CI 1.57–1.80, p

Background: Ventricular tachycardia (VT) recurrence after catheter ablation remains a concern, emphasizing the need for precise risk assessment. We aimed to use machine learning (ML) to predict 1-month and 1-year VT recurrence following VT ablation. Methods: For 337 patients undergoing VT ablation, we collected 31 parameters including medical history, echocardiography, and procedural data. 17 relevant features were included in the ML-based feature selection, which yielded six and five optimal features for 1-month and 1-year recurrence, respectively. We trained several supervised machine learning models using 10-fold cross-validation for each endpoint. Results: We observed 1-month VT recurrence was observed in 60 (18%) cases and accurately predicted using our model with an area under the receiver operating curve (AUC) of 0.73. Input features used were hemodynamic instability, incessant VT, ICD shock, left ventricular ejection fraction, TAPSE, and non-inducibility of the clinical VT at the end of the procedure. A separate model was trained for 1-year VT recurrence (observed in 117 (35%) cases) with a mean AUC of 0.71. Selected features were hemodynamic instability, the number of inducible VT morphologies, left ventricular systolic diameter, mitral regurgitation, and ICD shock. For both endpoints, a random forest model displayed the highest performance. Conclusions: Our ML models effectively predict VT recurrence post-ablation, aiding in identifying high-risk patients and tailoring follow-up strategies.

Aging is a major risk factor of atherosclerosis through different complex pathways including replicative cellular senescence and age-related clonal hematopoiesis. In addition to aging, extracellular stress factors, such as mechanical and oxidative stress, can induce cellular senescence, defined as premature cellular senescence. Senescent cells can accumulate within atherosclerotic plaques over time and contribute to plaque instability. This review summarizes the role of cellular senescence in the complex pathophysiology of atherosclerosis and highlights the most important senotherapeutics tested in cardiovascular studies targeting senescence. Continued bench-to-bedside research in cellular senescence might allow the future implementation of new effective anti-atherosclerotic preventive and treatment strategies in clinical practice.

Background: Chronic limb-threatening ischemia (CLTI) is associated with high rates of long-term cardiovascular mortality. Exercise stress testing to detect obstructive coronary artery disease (CAD) can be difficult in this subset of patients due to inability to undergo exercise testing, presence of balanced ischemia and severe coronary artery calcification (CAC). Aim: To test the feasibility of regadenoson stress dynamic perfusion computed tomography (DPCT) in CLTI patients. Methods: Between 2018 and 2023, coronary computed tomography angiography (CTA) and, in the case of a calcium score higher than 400, DPCT, were performed in 25 CLTI patients with a history of endovascular revascularization. Results: Of the 25 patients, 19 had a calcium score higher than 400, requiring DPCT image acquisition. Obstructive CAD could be ruled out in 10 of the 25 patients. Of the 15 CTA/DPCT+ patients, 13 proceeded to coronary angiography (CAG). Revascularization was necessary in all 13 patients. In these 13 patients, vessel-based sensitivity and specificity of coronary CTA/DPCT as compared to invasive evaluation was 75%, respectively. At follow-up (27 ± 21 months) there was no statistically significant difference in all-cause mortality between CTA/DPCT- positive and -negative patients (p = 0.065). Conclusions: Despite a high prevalence of severe CAC, coronary CTA complemented by DPCT may be a feasible method to detect obstructive and functionally significant CAD in CLTI patients.

The aim of the study was to investigate any indication of diminished orthostatic tolerance as a result of fatiguing intensive acute concentric exercise with a successive isometric wall-sit followed by an orthostatic stress test, with a special focus on any distinguishable alterations due to a delayed-onset muscle soreness effect. The exercise protocol was carried out among nineteen (10 female, 9 male) junior swimmers from the Hungarian National Swim Team. All athletes showed a positive orthostatic stress test right after our exercise protocol. The diastolic blood pressure was significantly lower due to the delayed-onset muscle soreness effect in the standing position after the supine position of the orthostatic stress test, in contrast to the athletes who did not experience delayed-onset muscle soreness. Furthermore, the heart rate was dysregulated in athletes with a delayed-onset muscle soreness effect when they assumed a supine position after the sustained standing position during the orthostatic stress test, in contrast to the athletes without delayed-onset muscle soreness. Interesting to note is that, in three subjects, the sustained standing position decreased the heart rate below the level of the initial supine position and six athletes experienced dizziness in the standing position, and all of these athletes were from the group that experienced delayed-onset muscle soreness. Accordingly, this study, for the first time, demonstrated that delayed-onset muscle soreness impairs orthostasis after unaccustomed fatiguing intensive acute concentric exercise with a successive isometric weight-loaded wall-sit; however, validation of this association should be investigated in a larger sample size.

Abstract Background We lack data on the effect of single premature ventricular contractions (PVCs) on the clinical and echocardiographic response after cardiac resynchronization therapy (CRT) device implantation. We aimed to assess the predictive value of PVCs at early, 1 month-follow up on echocardiographic response and all-cause mortality. Methods In our prospective, single-center study, 125 heart failure patients underwent CRT implantation based on the current guidelines. Echocardiographic reverse remodeling was defined as a ≥ 15% improvement in left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), or left atrial volume (LAV) measured 6 months after CRT implantation. All-cause mortality was investigated by Wilcoxon analysis. Results The median number of PVCs was 11,401 in those 67 patients who attended the 1-month follow-up. Regarding echocardiographic endpoints, patients with less PVCs develop significantly larger LAV reverse remodeling compared to those with high number of PVCs. During the mean follow-up time of 2.1 years, 26 (21%) patients died. Patients with a higher number of PVCs than our median cut-off value showed a higher risk of early all-cause mortality (HR 0.97; 95% CI 0.38–2.48; P = 0.04). However, when patients were followed up to 9 years, its significance diminished (HR 0.78; 95% CI 0.42–1.46; P = 0.15). Conclusions In patients undergoing CRT implantation, lower number of PVCs predicted atrial remodeling and showed a trend for a better mortality outcome. Our results suggest the importance of the early assessment of PVCs in cardiac resynchronization therapy and warrant further investigations.

BackgroundKidney transplantation (KTX) markedly improves prognosis in pediatric patients with end-stage kidney failure. Still, these patients have an increased risk of developing cardiovascular disease due to multiple risk factors. Three-dimensional (3D) echocardiography allows detailed assessment of the heart and may unveil distinct functional and morphological changes in this patient population that would be undetectable by conventional methods. Accordingly, our aim was to examine left- (LV) and right ventricular (RV) morphology and mechanics in pediatric KTX patients using 3D echocardiography.Materials and methodsPediatric KTX recipients (n = 74) with median age 20 (14–26) years at study enrollment (43% female), were compared to 74 age and gender-matched controls. Detailed patient history was obtained. After conventional echocardiographic protocol, 3D loops were acquired and measured using commercially available software and the ReVISION Method. We measured LV and RV end-diastolic volumes indexed to body surface area (EDVi), ejection fraction (EF), and 3D LV and RV global longitudinal (GLS) and circumferential strains (GCS).ResultsBoth LVEDVi (67 ± 17 vs. 61 ± 9 ml/m2; p

IntroductionDespite the significant contribution of circumferential shortening to the global ventricular function, data are scarce concerning its prognostic value on long-term mortality. Accordingly, our study aimed to assess both left (LV) and right ventricular (RV) global longitudinal (GLS) and global circumferential strain (GCS) using three-dimensional echocardiography (3DE) to determine their prognostic importance.MethodsThree hundred fifty-seven patients with a wide variety of left-sided cardiac diseases were retrospectively identified (64 ± 15 years, 70% males) who underwent clinically indicated 3DE. LV and RV GLS, and GCS were quantified. To determine the prognostic power of the different patterns of biventricular mechanics, we divided the patient population into four groups. Group 1 consisted of patients with both LV GLS and RV GCS above the respective median values; Group 2 was defined as patients with LV GLS below the median while RV GCS above the median, whereas in Group 3, patients had LV GLS values above the median, while RV GCS was below median. Group 4 was defined as patients with both LV GLS and RV GCS below the median. Patients were followed up for a median of 41 months. The primary endpoint was all-cause mortality.ResultsFifty-five patients (15%) met the primary endpoint. Impaired values of both LV GCS (HR, 1.056 [95% CI, 1.027–1.085], p < 0.001) and RV GCS (1.115 [1.068–1.164], p < 0.001) were associated with increased risk of death by univariable Cox regression. Patients with both LV GLS and RV GCS below the median (Group 4) had a more than 5-fold increased risk of death compared with those in Group 1 (5.089 [2.399–10.793], p < 0.001) and more than 3.5-fold compared with those in Group 2 (3.565 [1.256–10.122], p = 0.017). Interestingly, there was no significant difference in mortality between Group 3 (with LV GLS above the median) and Group 4, but being categorized into Group 3 versus Group 1 still held a more than 3-fold risk (3.099 [1.284–7.484], p = 0.012).DiscussionThe impaired values of both LV and RV GCS are associated with long-term all-cause mortality, emphasizing the importance of assessing biventricular circumferential mechanics. Reduced RV GCS is associated with significantly increased risk of mortality even if LV GLS is preserved.

BackgroundReports of left ventricular noncompaction (LVNC) rarely include descriptions of the right ventricle (RV). This study aimed to describe the characteristics of the RV in LVNC patients with reduced LV function (LVNC-R) compared with patients with dilated cardiomyopathy (DCM) and subjects with LVNC with normal left ventricular ejection fraction (LV-EF) (LVNC-N).MethodsForty-four LVNC-R patients, 44 LVNC-N participants, and 31 DCM patients were included in this retrospective study (LV-EF: LVNC-R: 33.4±10.2%; LVNC-N: 65.0±5.9%; DCM: 34.6±7.9%). Each group was divided into two subgroups by the amount of RV trabeculation.ResultsThere was no difference in the RV-EF between the groups, and the RV trabecular mass correlated positively with the RV volume and negatively with the RV-EF in all the groups. All the measured parameters were comparable between the groups with decreased LV function. The hypertrabeculated RV subgroups showed significantly higher RV volumes and lower RV-EF only in the decreased-LV-function groups. The correlation of LV and RV trabeculation was observed only in the LVNC-N group, while LV trabeculation correlated with RV volumes in both noncompacted groups. Both decreased-LV-function groups had worse RV strain values than the LVNC-N group; however, RV strain values correlated with RV trabeculation predominantly in the LVNC-R group.ConclusionsThe presence and characteristics of RV hypertrabeculation and the correlations between LV trabeculation and RV parameters raise the possibility of RV involvement in noncompaction; moreover, RV strain values might be helpful in the early detection of RV function deterioration.

Cardiac resynchronization therapy (CRT) for selected heart failure (HF) patients improves symptoms and reduces morbidity and mortality; however, the prognosis of HF is still poor. There is an emerging need for tools that might help in optimal patient selection and provide prognostic information for patients and their families. Several risk scores have been created in recent years; although, no literature review is available that would list the possible scores for the clinicians. We identified forty-eight risk scores in CRT and provided the calculation methods and formulas in a ready-to-use format. The reviewed score systems can predict the prognosis of CRT patients; some of them have even provided an online calculation tool. Significant heterogeneity is present between the various risk scores in terms of the variables incorporated and some variables are not yet used in daily clinical practice. The lack of cross-validation of the risk scores limits their routine use and objective selection. As the number of prognostic markers of CRT is overwhelming, further studies might be required to analyze and cross-validate the data.

AimsPrimary prevention of sudden cardiac death (SCD) in non-ischemic heart failure (HF) patients remains a topic of debate at cardiac resynchronization therapy (CRT) implantation requiring individual risk assessment. Using the Goldenberg SCD risk score, we aimed to predict, which non-ischemic HF patients will benefit from the addition of an implantable cardioverter defibrillator (ICD) to CRT at long-term.MethodsBetween 2000 and 2018 non-ischemic HF patients undergoing CRT implantation were collected into our retrospective registry. The Goldenberg risk score (GRS) was calculated by the presence of atrial fibrillation, New York Heat Association (NYHA) class > 2, age > 70 years, blood urea nitrogen > 26 mg/dl and QRS > 120 ms. The primary endpoint was all-cause mortality, heart transplantation or left ventricular assist device implantation.ResultsFrom 667 patients, 347 (52%) underwent cardiac resynchronization therapy-pacemaker (CRT-P), 320 (48%) cardiac resynchronization therapy-defibrillator (CRT-D) implantations. During the median follow up time of 4.3 years, 306 (46%) patients reached the primary endpoint (CRT-D 37% vs. CRT-P 63%; p < 0.001). CRT-D patients were younger (64 vs. 69 years; p < 0.001), infrequently females (26 vs. 39%; p < 0.001), and had a lower ejection fraction (27 vs. 29%; p < 0.01) compared to CRT-P patients. After GRS calculation, patients were dichotomized by low (< 3) and high (≥ 3) scores. CRT-D patients with low GRS showed a mortality benefit compared to CRT-P (HR 0.68; 95% CI 0.48–0.96; p = 0.03), high-risk patients did not (HR 0.84; 95% CI 0.62–1.13; p = 0.26).ConclusionIn our non-ischemic cohort, patients with low GRS showed a clear long-term mortality benefit by adding ICD to CRT, however, in high-risk patients no further benefit could be observed.

Abstract Background Oxidative stress is an important factor in the pathomechanism of atherosclerosis. Advanced oxidation protein products (AOPPs) are considered markers of oxidative stress. Thickening of the carotid intima-media layers indicates subclinical atherosclerosis and can be detected by carotid ultrasound. Objective Our aim was to examine the association between carotid intima-media thickness (CIMT) and the level of AOPPs. Methods Carotid duplex scans and measurements of AOPPs were performed on 476 participants of a cardiovascular population study. The presence of conventional cardiovascular risk factors was investigated with a questionnaire, physical examination, and laboratory tests. Results There was a positive correlation between maximum CIMT and the level of AOPPs only in the male population (r = 0.219, p = 0.033). Multivariate analysis has revealed that the association between AOPPs and mean or maximum CIMT was independent of cardiovascular risk factors (OR = 1.458, p = 0.004, and OR = 2.038, p

Right ventricular function strongly predicts cardiac death and adverse cardiac events in patients with cardiac diseases. However, the accurate right ventricular assessment by two-dimensional echocardiography is limited due to its complex anatomy, shape, and load dependence. Advances in cardiac imaging and three-dimensional echocardiography provided more reliable information on right ventricular volumes and function without geometrical assumptions. Furthermore, the pathophysiology of right ventricular dysfunction and tricuspid regurgitation is frequently connected. Three-dimensional echocardiography allows a more in-depth structural and functional evaluation of the tricuspid valve. Understanding the anatomy and pathophysiology of the right side of the heart may help in diagnosing and managing the disease by using reliable imaging tools. The present review describes the challenging echocardiographic assessment of the right ventricle and tricuspid valve apparatus in clinical practice with a focus on three-dimensional echocardiography.

This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.

Objectives The aim was to compare the prevalence of acute infection and seropositivity of SARS-CoV-2 among healthcare workers (HCWs) and medical students. Material and Methods A high-volume, single-center analysis was conducted in the period of July 1‒August 1, 2020, at the Semmelweis University. Naso- and oropharyngeal samples were collected for polymerase chain reaction (PCR), and blood samples for anti-SARS-CoV-2 IgG. A questionnaire was also administered about the infection symptoms and the obtained results were assessed by profession and site of care delivery. Results From the total cohort (N = 7948), 4478 (56%) and 3470 (44%) were health professionals and medical students, respectively. They were mainly female (67%), and the mean age of HCWs and students was 40 and 25 years, respectively. By profession, physicians (1.5%) and other HCWs (1.8%) showed a comparable SARS-CoV-2 exposure. International students had the highest (2.1%), whereas Hungarian students had the lowest (0.6%) prevalence of seropositivity. The highest prevalence was detected among the staff of COVID-19 wards (12.1%). By PCR, medical students showed the lowest occurrence of active infection with a prevalence of 0.17%, while physicians and other HCWs had a higher prevalence (1.46% and 1.71%, respectively). By site of care delivery, positive test results were the most frequent at COVID-19 wards (3.8%). Conclusions Physicians and other HCWs showed comparable SARS-CoV-2 seropositivity prevalence, approximately twice as high as in the general population of Budapest. Hungarian students had lower prevalence of seropositivity than this reference. High prevalence among international students suggests that they had imported the infection. The very high prevalence of documented exposure among staff members at COVID-19 wards urges for improving the safety measures. Int J Occup Med Environ Health. 2022;35(2):209–16