Search

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 ).

Graphical Abstract

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.

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.

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.

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.

This study aims to help educators and researchers to understand the pedagogical practice of STEM in early childhood and its impact. To support this, 29 publications related to STEM teachinglearning methods and activities were selected in the period between 2014 and 2023. The study covers the distribution of research over time by countries, the analysis of keywords, research goals and results, research methods, STEM domains, as well as emerging teaching-learning methods and activities, and the presentation of research limitations. According to the results, digital activities and impact studies have become dominant in early childhood STEM activities. There is a small number of studies presenting educational practices related to the relationship between sustainability and STEM. It was also revealed that impact assessments regarding early childhood STEM education need further development and improvement. [ABSTRACT FROM AUTHOR]

Aims Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm. Methods and results Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26–7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02–0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07–0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16–0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference −49.21 mL; 95% CI −69.10 to −29.32; P < 0.001; interaction P = 0.21). Conclusion In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR. [ABSTRACT FROM AUTHOR]

The growing popularity of mobile technologies in educational settings, from grade schools through college, has prompted science educators to prepare preservice teachers to successfully integrate technology into science teaching. This mixed-methods study explores the effectiveness of a mobile technology-based physics curriculum, Exploring Physics, on preservice elementary teachers' technology self-efficacy. Participants included 67 preservice elementary teachers enrolled in a specialized physics content course at a large public university in the United States. The experimental group (N = 34) used the Exploring Physics curriculum on iPads, and the comparison group (N = 33) used a hard-copy version of a similar curriculum. Data sources included a technology self-efficacy survey administered as pre- and posttests, focus group and individual interviews with 24 participants at two time points, weekly classroom observations, and artifacts. Data analyses included repeated measures analysis of variance and posthoc t tests with Bonferroni adjustments and grounded theory techniques. The results showed significant positive changes in the experimental group participants' technology self-efficacy. In contrast, there was a significant decrease in the comparison group participants' technology self-efficacy. Several affordances of the curriculum assisted the experimental group participants in developing an appreciation for using mobile technologies in science teaching. Implications for preservice teacher preparation for technology integration in science teaching are discussed.

The use of technology is increasing rapidly in our society, and classroom teachers must recognize the impact and importance of technology in the lives of their students. It is crucial that college faculty involved in teacher training design courses that integrate mobile technologies to prepare the next generation of teachers. In this study, we investigate the effectiveness of an iPad-based curriculum app, Exploring Physics, to enhance preservice elementary teachers' physics conceptual understanding in a physical science content course. Data were collected using a pre-and postPhysics Conceptual Understanding (PCU) survey and open-ended questionnaires. We found significant statistical gains in participants' (N = 73) physics conceptual understanding at the end of the course. Qualitative findings suggest that the learning experience allowed participants to experience the pedagogical affordances of mobile technologies as learners and future teachers and found themselves to be more comfortable with the idea of integrating technology into their future classrooms. The results of this study provide insights into the importance of providing preservice teachers with opportunities to experience the use of mobile technologies in their teacher preparation programs.

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

The proinflammatory cascade that is activated at the time of brain death plays a crucial role in organ procurement. Our aim of this study was to explore the relationship between the clinical outcome of orthotopic heart transplantation, as well as cytokine and apolipoprotein profiles of the pericardial fluid obtained at donation. Interleukin, adipokine and lipoprotein levels in the pericardial fluid, as well as clinical data of twenty donors after brain death, were investigated. Outcome variables included primary graft dysfunction, the need for posttransplantation mechanical cardiac support and International Society for Heart and Lung Transplantation grade ≥ 2R rejection. Hormone management and donor risk scores were also investigated. Lower levels of IL-6 were observed in primary graft dysfunction (median: 36.72 [IQR: 19.47–62.90] versus 183.67 [41.21–452.56]; p = 0.029) and in the need for mechanical cardiac support (44.12 [20.12–85.70] versus 247.13 [38.51–510.38]; p = 0.043). Rejection was associated with lower ApoAII (p = 0.021), ApoB100 (p = 0.032) and ApoM levels (p = 0.025). Lower adipsin levels were detected in those patients receiving desmopressin (p = 0.037); moreover, lower leptin levels were found in those patients receiving glucocorticoid therapy (p = 0.045), and higher T3 levels were found in those patients treated with L-thyroxine (p = 0.047) compared to those patients not receiving these hormone replacement therapies. IL-5 levels were significantly associated with UNOS-D score (p = 0.004), Heart Donor Score (HDS) and Adapted HDS (p < 0.001). The monitoring of immunological and metabolic changes in donors after brain death may help in the prediction of potential complications after heart transplantation, thus potentially optimizing donor heart allocation.

The best method of anticoagulation for patients with peripheral artery disease (PAD) is still a topic of interest for physicians. We conducted a meta-analysis to compare the effects of direct oral anticoagulants (DOACs) with those of vitamin-K-antagonist (VKA) anticoagulants in patients with peripheral artery disease. Five databases (Medline (via PubMed), EMBASE, Scopus, Web of Science, and CENTRAL) were searched systematically for studies comparing the effects of the two types of anticoagulants in patients with PAD, with an emphasis on lower-limb outcomes, cardiovascular events, and mortality. In PAD patients with concomitant non-valvular atrial fibrillation (NVAF), the use of DOACs significantly reduced the risk of major adverse limb events (HR = 0.58, 95% CI, 0.39–0.86, p < 0.01), stroke/systemic embolism (HR 0.76; 95% CI 0.61–0.95; p < 0.01), and all-cause mortality (HR 0.78; 95% CI 0.66–0.92; p < 0.01) compared with warfarin, but showed similar risks of MI (HR = 0.81, 95% CI, 0.59–1.11, p = 0.2) and cardiovascular mortality (HR = 0.77, 95% CI, 0.58–1.02, p = 0.07). Rivaroxaban at higher doses significantly increased the risk of major bleeding (HR = 1.16, 95% CI, 1.07–1.25, p < 0.01). We found no significant difference in terms of revascularization (OR = 1.49, 95% CI, 0.79–2.79, p = 0.14) in PAD patients in whom a poor distal runoff was the reason for the anticoagulation. DOACs have lower rates of major limb events, stroke, and mortality than VKAs in PAD patients with atrial fibrillation. Rivaroxaban at higher doses increased the risk of major bleeding compared with other DOAC drugs. More high-quality studies are needed to determine the most appropriate anticoagulation regimen for patients with lower-limb atherosclerosis.

Due to the lifelong nature of diabetes mellitus (DM), it has been demonstrated to have significant effects on patients’ morbidity and mortality. The present study aimed to assess the effects of DM on the clinical outcome and survival in patients who underwent percutaneous coronary intervention (PCI) due to myocardial infarction (MI) and to examine the relationship of DM to the type of the MI and to left ventricular (LV) and renal functions. A total of 12,270 patients with ST-elevation MI (STEMI) or non-ST-elevation MI (NSTEMI) were revascularized at our Institution between 2005 and 2013. In this pool of patients, 4388 subjects had DM, while 7018 cases had no DM. In both STEMI and NSTEMI, the 30-day and 1-year survival were worse in diabetic patients as compared to non-diabetic cases. In the patients with DM, NSTEMI showed worse prognosis within 1-year than STEMI similarly to non-diabetic subjects. Regarding survival, the presence of DM seemed to be more important than the type of MI. Regardless of the presence of DM, reduced LV function was a maleficent prognostic sign and DM significantly reduced the prognosis both in case of reduced and normal LV function. Survival is primarily affected by LV function, rather than DM. Worse renal function is associated with worse 30-day and 1-year survival in both cases with and without DM. Considering different renal functions, the presence of DM worsens both short- and long-term survival. Survival is primarily affected by renal function, rather than DM. The results from a high-volume PCI center confirm significant the negative prognostic impact of DM on survival in MI patients. DM is a more important prognostic factor than the type of the MI. However, survival is primarily affected by LV and renal functions, rather than DM. These results could highlight our attention on the importance of recent DM treatment with new drugs including SGLT-2 inhibitors and GLP-1 antagonists with beneficial effects on survival.

Abstract Aims Preferring side branch of coronary sinus during cardiac resynchronization therapy (CRT) implantation has been empirical due to the limited data on the association of left ventricular (LV) lead position and long‐term clinical outcome. We evaluated the long‐term all‐cause mortality by LV lead non‐apical positions and further characterized them by interlead electrical delay (IED). Methods and results In our retrospective database, 2087 patients who underwent CRT implantation were registered between 2000 and 2018. Those with non‐apical LV lead locations were classified into anterior (n = 108), posterior (n = 643), and lateral (n = 1336) groups. All‐cause mortality was assessed by Kaplan–Meier and Cox analyses. Echocardiographic response was measured 6 months after CRT implantation. During the median follow‐up time of 3.7 years, 1150 (55.1%) patients died—710 (53.1%) with lateral, 78 (72.2%) with anterior, and 362 (56.3%) with posterior positions. When we investigated the risk of all‐cause mortality, there was a significantly lower rate of death in patients with lateral LV lead location when compared with those with an anterior (P

Background: The relative importance of variables explaining sex-related differences in outcomes is scarcely explored in patients undergoing cardiac resynchronization therapy (CRT). We sought to implement and evaluate machine learning (ML) algorithms for the prediction of 1- and 3-year all-cause mortality in CRT patients. We also aimed to assess the sex-specific differences in predictors of mortality utilizing ML.Methods: Using a retrospective registry of 2,191 CRT patients, ML models were implemented in 6 partially overlapping patient subsets (all patients, females, or males with 1- or 3-year follow-up). Each cohort was randomly split into training (80%) and test sets (20%). After hyperparameter tuning in the training sets, the best performing algorithm was evaluated in the test sets. Model discrimination was quantified using the area under the receiver-operating characteristic curves (AUC). The most important predictors were identified using the permutation feature importances method.Results: Conditional inference random forest exhibited the best performance with AUCs of 0.728 (0.645–0.802) and 0.732 (0.681–0.784) for the prediction of 1- and 3-year mortality, respectively. Etiology of heart failure, NYHA class, left ventricular ejection fraction, and QRS morphology had higher predictive power, whereas hemoglobin was less important in females compared to males. The importance of atrial fibrillation and age increased, while the importance of serum creatinine decreased from 1- to 3-year follow-up in both sexes.Conclusions: Using ML techniques in combination with easily obtainable clinical features, our models effectively predicted 1- and 3-year all-cause mortality in CRT patients. Sex-specific patterns of predictors were identified, showing a dynamic variation over time.