Publications by authors named "Béla Merkely"

621 Publications

The application of landiolol in the cardiovascular and intensive care

Orv Hetil 2022 01 9;163(2):53-62. Epub 2022 Jan 9.

2 Semmelweis Egyetem, Általános Orvostudományi Kar, Városmajori Szív- és Érgyógyászati Klinika Budapest, Városmajor u. 68., 1122.

Összefoglaló. A landiolol intravénásan alkalmazandó, kifejezetten cardioselectiv, gyors hatású és rövid felezési idejű béta-1-receptor-blokkoló, mely elsősorban negatív chronotrop és inotrop hatással bír, vérnyomáscsökkentő hatása elhanyagolható. Főleg hemodinamikailag instabil állapotú, supraventricularis ritmuszavarban szenvedő betegek kamrafrekvenciájának csökkentésére használható. Nagy esetszámú, randomizált vizsgálatok igazolták hatékonyságát szívműtétek után jelentkező pitvarfibrilláció megelőzésében, valamint súlyos akut szívelégtelenségben és szívműtétek posztoperatív szakában jelentkező pitvari tachyarrhythmiák kezelésében. Ezek mellett kisebb vizsgálatok alapján a használata biztonságosnak tűnik akut myocardialis infarctusban, hatékony szeptikus állapotú, pitvarfibrillációban szenvedő betegek kamrafrekvencia- és ritmuskontrolljára, valamint nem cardialis műtétek esetén a pitvarfibrilláció prevenciójára és kezelésére. Sikerrel alkalmazható elektromos vihar esetén is, és jól használható angiográfiás coronaria-CT-vizsgálat előtt az optimális szívfrekvencia elérésére. A gyógyszer 2016 óta Európában, 2018 óta Magyarországon is elérhető. Orv Hetil. 2022; 163(2): 53-62. Summary. Landiolol is an intravenous, selective beta-1-receptor blocking agent with rapid onset of action and ultra-short half-life that has a predominant negative chronotropic and only mild negative inotropic effect without significant reduction of blood pressure. Landiolol is indicated to control the ventricular heart rate predominantly in patients with hemodynamic instability due to supraventricular tachyarrhythmia. Large randomized controlled trials have proven the efficacy of landiolol in the prevention of atrial fibrillation and atrial tachyarrhythmias in severe acute heart failure or post-cardiac surgery. Based on lower case-number studies, the administration of landiolol has been proven to be efficient and safe in rhythm and rate control in atrial fibrillation complicating acute myocardial infarction, sepsis, and in the prevention of atrial fibrillation in non-cardiac surgery. Landiolol may be used in electrical storm, and even during coronary CT-angiography to achieve an optimal heart rate for imaging. The drug is available in Europe since 2016 and in Hungary since 2018. Orv Hetil. 2022; 163(2): 53-62.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/650.2022.32347DOI Listing
January 2022

Level of advanced oxidation protein products is associated with subclinical atherosclerosis.

BMC Cardiovasc Disord 2022 Jan 8;22(1). Epub 2022 Jan 8.

Heart and Vascular Center, Semmelweis University, Városmajor utca 68, Budapest, 1122, Hungary.

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 < 0.001).

Conclusions: Among males, the elevated level of AOPPs as a marker of oxidative stress may signal the existence of early atherosclerotic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-02451-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742310PMC
January 2022

Sex differences in rat renal arterial responses following exercise training.

Am J Physiol Heart Circ Physiol 2022 Jan 7. Epub 2022 Jan 7.

Department of Obstetrics and Gynaecology, Semmelweis University, Budapest, Hungary.

During aerobic exercise, hemodynamic alterations occure; while blood flow in skeletal muscle arteries increases, it decreases in visceral vessels due to mesenterial vasoconstriction. However, maintaining renal blood flow during intensive sport is also a priority. Our aim was to investigate the changes of vascular reactivity and histology of isolated renal artery of male and female rats in response to swim-training. Wistar rats were distributed into four groups: male sedentary (MSed), male trained (MTr), female sedentary (FSed), and female trained (FTr). Trained animals underwent a 12-week-long intensive swimming program. Vascular function of isolated renal artery segments was examined by wire myography. Phenylephrine-induced contraction was lower in FSed compared to MSed animals, and it was decreased by training in male but not in female animals. Inhibition of cyclooxygenases by indomethacin reduced contraction in both sedentary groups, and in MTr but not in FTr animals. Inhibition of nitric oxide production increased contraction in both trained groups. Acetylcholine induced relaxation was similar in all experimental groups showing predominant NO-dependency. Elastin and smooth muscle cell actin density was reduced in female rats after aerobic training. This study shows that, as a result of 12-weeks-long training, there are sex differences in renal arterial responses following exercise training. Swimming moderates renal artery vasoconstriction in male animals, while it depresses elastic fiber and smooth muscle actin density in females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00398.2021DOI Listing
January 2022

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting.

Geroscience 2022 Jan 5. Epub 2022 Jan 5.

Department of Pulmonology, Semmelweis University, Budapest, Hungary.

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient's activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11357-021-00512-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729098PMC
January 2022

Acute SARS-CoV-2 infection and seropositivity among healthcare workers and medical students in summer 2020, Hungary.

Int J Occup Med Environ Health 2021 Dec 15. Epub 2021 Dec 15.

Semmelweis University, Budapest, Hungary (Center for Health Technology Assessment).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13075/ijomeh.1896.01804DOI Listing
December 2021

Exercise-induced alterations of myocardial sarcomere dynamics are associated with hypophosphorylation of cardiac troponin I.

Rev Cardiovasc Med 2021 Dec;22(4):1079-1085

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Although the knowledge of sports cardiology advanced significantly in the recent years, the molecular mechanisms by which exercise training augments cardiac performance is poorly understood. Here we aimed at determining left ventricular (LV) myocardial sarcomeric protein modifications in a rat model of exercise training and detraining. Young male Wistar rats were divided into exercised (Ex) and control (Co) groups. Trained rats swam 200 min/day for 12 weeks. Detrained (DEx) and control (DCo) rats remained sedentary for 8 weeks after completion of the 12-week-long protocol. Ca-regulated active force production (F), its Ca-sensitivity (pCa) and Ca-independent passive tension (F) were determined in isolated permeabilized cardiomyocytes and phosphorylation levels of sarcomeric proteins were assayed by biochemical methods. Means of maximal Ca-activated isometric force (F) and pCa50 values were higher ( < 0.05) in the Ex group (28.0 ± 1.4 kN/m and 5.91 ± 0.03, respectively, mean ± SEM) than those in the Co group (15.8 ± 0.8 kN/m and 5.81 ± 0.03, respectively). F did not differ between these two groups. The level of cardiac troponin I (cTnI) phosphorylation decreased upon exercise (from 1.00 ± 0.02 to 0.66 ± 0.06, < 0.05; in relative units). Site specific phosphorylation assays revealed cTnI hypophosphorylations at the protein kinase A (PKA)-specific Ser-22/23 sites and at the protein kinase C (PKC)-specific Thr-143 site. Mechanical and biochemical parameters of the DEx and DCo groups did not differ from each other following the detraining period. Exercise-induced hypertrophy is associated with reversible increases in Ca-dependent force production and its Ca-sensitivity in LV cardiomyocytes, which can be associated with changes in cTnI phosphorylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.31083/j.rcm2204119DOI Listing
December 2021

Age- and Sex-Specific Characteristics of Right Ventricular Compacted and Non-compacted Myocardium by Cardiac Magnetic Resonance.

Front Cardiovasc Med 2021 7;8:781393. Epub 2021 Dec 7.

Heart and Vascular Center of Semmelweis University, Budapest, Hungary.

The age and sex-specific characteristics of right ventricular compacted (RV-CMi) and RV-trabeculated myocardial mass (RV-TMi) and the determinants of RV myocardium are less well-studied; however, in different conditions, these might provide additional diagnostic information. We aimed to describe the age- and sex-specific characteristics of RV-CMi, RV-TMi, and RV volumetric and functional parameters and investigate the determinants of RV myocardial mass with cardiac magnetic resonance (CMR). Two hundred healthy Caucasian volunteers free of known cardiovascular or systemic diseases were prospectively enrolled in this study. Four different age groups were established with equal numbers of males and females: Group A ( = 50, 20-29 years, mean age: 24.3 ± 3.2 years), Group B ( = 50, 30-39 years, mean age: 33.6 ± 2.6 years), Group C ( = 50, 40-49 years, mean age: 44.7 ± 2.7 years), and Group D ( = 50, ≥50 years, mean age: 55.1 ± 3.9 years). Left ventricular (LV) and RV volumetric, functional, CMi, and TMi values were measured with a threshold-based post-processing CMR method. The volumetric parameters, RV-CMi, and RV-TMi values were larger, and the ejection fraction (EF) was lower in males. The RV-CMi did not correlate with age in either of the sexes, while the RV-TMi decreased with age in females but remained stable in males. The RV-TMi and RV-CMi correlated positively with RV volumetric parameters, the LV-CMi, the LV-TMi, and each other in both sexes. LV-TMi, LV-CMi, RV end-systolic volume, and sex were independent predictors of RV-TMi. Understanding the characteristics of RV-trabeculated and RV-compacted myocardium might have additive value in diagnosing different conditions with RV hypertrophy or hypertrabeculation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.781393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688768PMC
December 2021

Transcriptional co-activators YAP1-TAZ of Hippo signalling in doxorubicin-induced cardiomyopathy.

ESC Heart Fail 2021 Dec 21. Epub 2021 Dec 21.

Heart and Vascular Center, Semmelweis University, 68 Városmajor Street, Budapest, H1122, Hungary.

Aims: Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem cell self-renewal. Recently, the pathway has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, the functional role of this stress-related and cell death-related pathway in the human heart and cardiomyocytes is not known. In this study, we investigated the role of the transcriptional co-activators of Hippo signalling, YAP and TAZ, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in response to cardiotoxic agents and investigated the effects of modulating the pathway on cardiomyocyte function and survival.

Methods And Results: RNA-sequencing analysis of human heart samples with doxorubicin-induced end-stage heart failure and healthy controls showed that YAP and ERBB2 (HER2) as upstream regulators of differentially expressed genes correlated with doxorubicin treatment. Thus, we tested the effects of doxorubicin on hiPSC-CMs in vitro. Using an automated high-content screen of 96 clinically relevant antineoplastic and cardiotherapeutic drugs, we showed that doxorubicin induced the highest activation of YAP/TAZ nuclear translocation in both hiPSC-CMs and control MCF7 breast cancer cells. The overexpression of YAP rescued doxorubicin-induced cell loss in hiPSC-CMs by inhibiting apoptosis and inducing proliferation. In contrast, silencing of YAP and TAZ by siRNAs resulted in elevated mitochondrial membrane potential loss in response to doxorubicin. hiPSC-CM calcium transients did not change in response to YAP/TAZ silencing.

Conclusions: Our results suggest that Hippo signalling is involved in clinical anthracycline-induced cardiomyopathy. Modelling with hiPSC-CMs in vitro showed similar responses to doxorubicin as adult cardiomyocytes and revealed a potential cardioprotective effect of YAP in doxorubicin-induced cardiotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13756DOI Listing
December 2021

Semmelweis Caring University Model Program Based on the Development of a Center of Preventive Services: Health for All Employees at a University Occupational Setting.

Front Public Health 2021 29;9:727668. Epub 2021 Nov 29.

Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

The leadership of the Semmelweis University as a leading institution of higher education in Hungary and the Central Eastern European region within the area of medicine and health sciences has decided to reflect on the unfavorable public health situation in the country as well as the deteriorating health behavior and health status indicators in the Hungarian population by the development of an occupational setting-based personalized public health model program targeting its about 8500 employees. Based on its infrastructure and human resources the core element of the program is the establishment of the Center of Preventive Services (CPS) with units providing health risk assessment for each employee, and whenever necessary consultation with medical specialist in preventive medicine and public health, as well as counseling with dietician, physiotherapist and/or health psychologist. The service providers are the staff members of the relevant faculties in collaboration with partner primary and occupational care physicians. The units of the CPS can also serve as practical training sites for students at various levels of medical and health sciences training, and strongly contribute to the development and improvement of their skills to be able for working as a team in service provision. The employees are not only beneficiaries of health risk assessment and screening repeated on a regular basis and adequate interventions at the right time, but they also serve as a sample for a longitudinal cohort study and further surveys for defining and implementing interventions to support health protection, disease prevention and healthy aging among them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.727668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666717PMC
November 2021

Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia.

J Transl Med 2021 Dec 11;19(1):507. Epub 2021 Dec 11.

Experimental Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Városmajor u. 68, Budapest, 1122, Hungary.

Background: Reduced cardiovascular risk in premenopausal women has been the focus of research in recent decades. Previous hypothesis-driven experiments have highlighted the role of sex hormones on distinct inflammatory responses, mitochondrial proteins, extracellular remodeling and estrogen-mediated cardioprotective signaling pathways related to post-ischemic recovery, which were associated with better cardiac functional outcomes in females. We aimed to investigate the early, sex-specific functional and proteomic changes following myocardial ischemia in an unbiased approach.

Methods: Ischemia was induced in male (M-Isch) and female (F-Isch) rats with sc. injection of isoproterenol (85 mg/kg) daily for 2 days, while controls (M-Co, F-Co) received sc. saline solution. At 48 h after the first injection pressure-volume analysis was carried out to assess left ventricular function. FFPE tissue slides were scanned and analyzed digitally, while myocardial proteins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using isobaric labeling. Concentrations of circulating steroid hormones were measured with LC-MS/MS. Feature selection (PLS and PLS-DA) was used to examine associations among functional, proteomic and hormonal datasets.

Results: Induction of ischemia resulted in 38% vs 17% mortality in M-Isch and F-Isch respectively. The extent of ischemic damage to surviving rats was comparable between the sexes. Systolic dysfunction was more pronounced in males, while females developed a more severe impairment of diastolic function. 2224 proteins were quantified, with 520 showing sex-specific differential regulation. Our analysis identified transcriptional, cytoskeletal, contractile, and mitochondrial proteins, molecular chaperones and the extracellular matrix as sources of disparity between the sexes. Bioinformatics highlighted possible associations of estrogens and their metabolites with early functional and proteomic alterations.

Conclusions: Our study has highlighted sex-specific alterations in systolic and diastolic function shortly after ischemia, and provided a comprehensive look at the underlying proteomic changes and the influence of estrogens and their metabolites. According to our bioinformatic analysis, inflammatory, mitochondrial, chaperone, cytoskeletal, extracellular and matricellular proteins are major sources of intersex disparity, and may be promising targets for early sex-specific pharmacologic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-021-03164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666068PMC
December 2021

Evaluation of muscle-specific and metabolism regulating microRNAs in a chronic swimming rat model.

J Muscle Res Cell Motil 2021 Dec 10. Epub 2021 Dec 10.

Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei blvd. 98, PO Box 22, 4012, Debrecen, Hungary.

Making benefit from the epigenetic effects of environmental factors such as physical activity may result in a considerable improvement in the prevention of chronic civilization diseases. In our chronic swimming rat model, the expression levels of such microRNAs were characterized, that are involved in skeletal muscle differentiation, hypertrophy and fine-tuning of metabolism, which processes are influenced by chronic endurance training, contributing to the metabolic adaptation of skeletal muscle during physical activity. After chronic swimming, the level of miR-128a increased significantly in EDL muscles, which may influence metabolic adaptation and stress response as well. In SOL, the expression level of miR-15b and miR-451 decreased significantly after chronic swimming, which changes are opposite to their previously described increment in insulin resistant skeletal muscle. MiR-451 also targets PGC-1α mRNA, whiches expression level significantly increased in SOL muscles, resulting in enhanced biogenesis and oxidative capacity of mitochondria. In summary, the microRNA expression changes that were observed during our experiments suggest that chronic swim training contributes to a beneficial metabolic profile of skeletal muscle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10974-021-09612-yDOI Listing
December 2021

The diagnostic performance of deep-learning-based CT severity score to identify COVID-19 pneumonia.

Br J Radiol 2022 Jan;95(1129):20210759

Medical Imaging Centre, Semmelweis University, Budapest, Hungary.

Objective: To determine the diagnostic accuracy of a deep-learning (DL)-based algorithm using chest computed tomography (CT) scans for the rapid diagnosis of coronavirus disease 2019 (COVID-19), as compared to the reference standard reverse-transcription polymerase chain reaction (RT-PCR) test.

Methods: In this retrospective analysis, data of COVID-19 suspected patients who underwent RT-PCR and chest CT examination for the diagnosis of COVID-19 were assessed. By quantifying the affected area of the lung parenchyma, severity score was evaluated for each lobe of the lung with the DL-based algorithm. The diagnosis was based on the total lung severity score ranging from 0 to 25. The data were randomly split into a 40% training set and a 60% test set. Optimal cut-off value was determined using Youden-index method on the training cohort.

Results: A total of 1259 patients were enrolled in this study. The prevalence of RT-PCR positivity in the overall investigated period was 51.5%. As compared to RT-PCR, sensitivity, specificity, positive predictive value, negative predictive value and accuracy on the test cohort were 39.0%, 80.2%, 68.0%, 55.0% and 58.9%, respectively. Regarding the whole data set, when adding those with positive RT-PCR test at any time during hospital stay or "COVID-19 without virus detection", as final diagnosis to the true positive cases, specificity increased from 80.3% to 88.1% and the positive predictive value increased from 68.4% to 81.7%.

Conclusion: DL-based CT severity score was found to have a good specificity and positive predictive value, as compared to RT-PCR. This standardized scoring system can aid rapid diagnosis and clinical decision making.

Advances In Knowledge: DL-based CT severity score can detect COVID-19-related lung alterations even at early stages, when RT-PCR is not yet positive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20210759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722241PMC
January 2022

Is cardiac involvement prevalent in highly trained athletes after SARS-CoV-2 infection? A cardiac magnetic resonance study using sex-matched and age-matched controls.

Br J Sports Med 2021 Nov 30. Epub 2021 Nov 30.

Heart and Vascular Center, Semmelweis University, Budapest, Hungary

Objectives: To investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls.

Methods: SARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination. The CMR protocol contained sequences to assess structural, functional and tissue-specific data.

Results: One hundred forty-seven athletes (94 male, median 23, IQR 20-28 years) after SARS-CoV-2 infection were included. Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1). Only two (1.4%) athletes presented with definite signs of myocarditis. We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls. There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups. Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05). However, T1 mapping values remained below the cut-off point for most patients.

Conclusion: Among 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%. Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjsports-2021-104576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637606PMC
November 2021

Fibrin to von Willebrand factor ratio in arterial thrombi is associated with plasma levels of inflammatory biomarkers and local abundance of extracellular DNA.

Thromb Res 2022 Jan 18;209:8-15. Epub 2021 Nov 18.

Department of Biochemistry, Semmelweis University, Budapest, Hungary. Electronic address:

Introduction: The composition of thrombi determines their structure, mechanical stability, susceptibility to lysis, and consequently, the clinical outcome in coronary artery disease (CAD), acute ischemic stroke (AIS), and peripheral artery disease (PAD). Fibrin forms the primary matrix of thrombi intertwined with DNA, derived from neutrophil extracellular traps (NETs), and von Willebrand factor (VWF) bridging DNA and platelets. Here we examined the relative content of fibrin, DNA and VWF in thrombi and analyzed their interrelations and quantitative associations with systemic biomarkers of inflammation and clinical characteristics of the patients.

Patients, Methods: Thrombi extracted from AIS (n = 17), CAD (n = 18) or PAD (n = 19) patients were processed for scanning electron microscopy, (immune)stained for fibrin, VWF and extracellular DNA. Fibrin fiber diameter, cellular components, fibrin/DNA and fibrin/VWF ratios were measured.

Results: Patients' age presented as a strong explanatory factor for a linear decline trend of the VWF content relative to fibrin in thrombi from CAD (adjusted-R = 0.43) and male AIS (adjusted-R = 0.66) patients. In a subgroup of CAD and PAD patients with dyslipidemia and high (above 80%) prevalence of atherothrombosis a significant correlation was observed between the VWF and DNA content in thrombi (adjusted-R = 0.40), whereas a 3.7-fold lower linear regression coefficient was seen in AIS patients, in whom the fraction of thrombi of atherosclerotic origin was 57%. Independently of anatomical location, in patients with atherosclerosis the VWF in thrombi correlated with the plasma C-reactive protein levels.

Conclusions: The observed interrelations between thrombus constituents and systemic inflammatory biomarkers suggest an intricate interplay along the VWF/NET/fibrin axis in arterial thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2021.11.011DOI Listing
January 2022

The Predictive Role of Artificial Intelligence-Based Chest CT Quantification in Patients with COVID-19 Pneumonia.

Tomography 2021 11 1;7(4):697-710. Epub 2021 Nov 1.

Medical Imaging Centre, Semmelweis University, 1082 Budapest, Hungary.

We sought to analyze the prognostic value of laboratory and clinical data, and an artificial intelligence (AI)-based algorithm for Coronavirus disease 2019 (COVID-19) severity scoring, on CT-scans of patients hospitalized with COVID-19. Moreover, we aimed to determine personalized probabilities of clinical deterioration. Data of symptomatic patients with COVID-19 who underwent chest-CT-examination at the time of hospital admission between April and November 2020 were analyzed. COVID-19 severity score was automatically quantified for each pulmonary lobe as the percentage of affected lung parenchyma with the AI-based algorithm. Clinical deterioration was defined as a composite of admission to the intensive care unit, need for invasive mechanical ventilation, use of vasopressors or in-hospital mortality. In total 326 consecutive patients were included in the analysis (mean age 66.7 ± 15.3 years, 52.1% male) of whom 85 (26.1%) experienced clinical deterioration. In the multivariable regression analysis prior myocardial infarction (OR = 2.81, 95% CI = 1.12-7.04, = 0.027), immunodeficiency (OR = 2.08, 95% CI = 1.02-4.25, = 0.043), C-reactive protein (OR = 1.73, 95% CI = 1.32-2.33, < 0.001) and AI-based COVID-19 severity score (OR = 1.08; 95% CI = 1.02-1.15, = 0.013) appeared to be independent predictors of clinical deterioration. Personalized probability values were determined. AI-based COVID-19 severity score assessed at hospital admission can provide additional information about the prognosis of COVID-19, possibly serving as a useful tool for individualized risk-stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/tomography7040058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628928PMC
November 2021

Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts.

Antioxidants (Basel) 2021 Nov 6;10(11). Epub 2021 Nov 6.

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV) dysfunction are frequent complications of diabetic cardiomyopathy. Here we aimed to characterize RV and left ventricular (LV) remodeling and its prevention by vardenafil (a long-acting phosphodiesterase-5A (PDE-5A) inhibitor) administration in a diabetic HFpEF model. Zucker Diabetic Fatty (ZDF) and control, ZDF Lean (Lean) male rats received 10 mg/kg vardenafil (ZDF + Vard; Lean + Vard) per os, on a daily basis for a period of 25 weeks. In vitro force measurements, biochemical and histochemical assays were employed to assess cardiomyocyte function and signaling. Vardenafil treatment increased cyclic guanosine monophosphate (cGMP) levels and decreased 3-nitrotyrosine (3-NT) levels in the left and right ventricles of ZDF animals, but not in Lean animals. Cardiomyocyte passive tension (F) was higher in LV and RV cardiomyocytes of ZDF rats than in those receiving preventive vardenafil treatment. Levels of overall titin phosphorylation did not differ in the four experimental groups. Maximal Ca-activated force (F) of LV and RV cardiomyocytes were preserved in ZDF animals. Ca-sensitivity of isometric force production (pCa) was significantly higher in LV (but not in RV) cardiomyocytes of ZDF rats than in their counterparts in the Lean or Lean + Vard groups. In accordance, the phosphorylation levels of cardiac troponin I (cTnI) and myosin binding protein-C (cMyBP-C) were lower in LV (but not in RV) cardiomyocytes of ZDF animals than in their counterparts of the Lean or Lean + Vard groups. Vardenafil treatment normalized pCa values in LV cardiomyocytes, and it decreased pCa below control levels in RV cardiomyocytes in the ZDF + Vard group. Our data illustrate partially overlapping myofilament protein alterations for LV and RV cardiomyocytes in diabetic rat hearts upon long-term PDE-5A inhibition. While uniform patterns in cGMP, 3-NT and F levels predict identical effects of vardenafil therapy for the diastolic function in both ventricles, the uneven cTnI, cMyBP-C phosphorylation levels and pCa values implicate different responses for the systolic function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10111776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615283PMC
November 2021

Predictors of mortality following extracorporeal membrane oxygenation support in an unselected, critically ill patient population.

Postepy Kardiol Interwencyjnej 2021 Sep 13;17(3):290-297. Epub 2021 Sep 13.

Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

Introduction: Mechanical circulatory support (MCS) has been established as a means of augmenting circulation in patients with critically decreased systolic function due to a variety of underlying clinical reasons. Different methods of MCS may be used, with the venous-arterial extracorporeal membrane oxygenation system (VA-ECMO) being one of the most utilized devices in everyday care.

Aim: To determine independent predictors influencing mortality outcomes following VA-ECMO therapy in a large, unselected, adult, critically ill patient population in cardiogenic shock (CS).

Material And Methods: Data on 235 consecutive, real-world VA-ECMO treatments were assessed. Analysis was conducted for all subjects requiring MCS with the VA-ECMO as the first instalment, regardless of underlying cause or eventual upgrade. All potential clinical factors influencing mortality were examined and evaluated.

Results: Overall mortality was ~66% at median 28 days follow-up and significantly depended upon pH < 7.3 (HR = 3.56; < 0.001), and age ≥ 65 years (HR = 1.96; = 0.001). Acute coronary syndrome (ACS) as an indication for VA-ECMO displayed a nearly significant value (HR = 1.44; = 0.07). Heart transplant (hTX) primary graft failure as an indication for the VA-ECMO displayed a clearly favorable outcome (HR = 0.51, = 0.025); all data based on multivariate Cox regression analysis.

Conclusions: Mortality in patients requiring VA-ECMO remains high. We conclude that only decreased pH values and advanced age clearly influence mortality in this MCS scenario. ACS also bodes unfavorably, whereas hTX as an indication clearly shows better survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/aic.2021.109149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596723PMC
September 2021

Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling.

Circulation 2021 12 22;144(25):2021-2034. Epub 2021 Nov 22.

King's BHF Centre of Research Excellence, London, UK (J.B.-B., M.F., U.M., W.-Y.L., E.E., E.D., M.H., L.E.S., B.S., R.L., F.B., A.M.S., N.C., K.T., A.M.S., M.M.).

Background: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown.

Methods: Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF.

Results: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5 mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin β1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5 mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with β-blockers had a distinct cardiac ECM profile.

Conclusions: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687617PMC
December 2021

Model-based adaptive filter for a dedicated cardiovascular CT scanner: Assessment of image noise, sharpness and quality.

Eur J Radiol 2021 Dec 15;145:110032. Epub 2021 Nov 15.

MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68. Varosmajor st., 1122 Budapest, Hungary.

Background: Filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASIR) are ubiquitously applied in the reconstruction of coronary CT angiography (CCTA) datasets. However, currently no data is available on the impact of a model-based adaptive filter (MBAF2), recently developed for a dedicated cardiac scanner.

Purpose: Our aim was to determine the effect of MBAF2 on subjective and objective image quality parameters of coronary arteries on CCTA.

Methods: Images of 102 consecutive patients referred for CCTA were evaluated. Four reconstructions of coronary images (FBP, ASIR, MBAF2, ASIR + MBAF2) were co-registered and cross-section were assessed for qualitative (graininess, sharpness, overall image quality) and quantitative [image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)] image quality parameters. Image noise and signal were measured in the aortic root and the left main coronary artery, respectively. Graininess, sharpness, and overall image quality was assessed on a 4-point Likert scale.

Results: As compared to FBP, ASIR, and MBAF2, ASIR + MBAF2 resulted in reduced image noise [53.1 ± 12.3, 30.6 ± 8.5, 36.3 ± 4.2, 26.3 ± 4.0 Hounsfield units (HU), respectively; p < 0.001], improved SNR (8.4 ± 2.6, 14.1 ± 3.6, 11.8 ± 2.3, 16.3 ± 3.3 HU, respectively; p < 0.001) and CNR (9.4 ± 2.7, 15.9 ± 4.0, 13.3 ± 2.5, 18.3 ± 3.5 HU, respectively; p < 0.001). No difference in sharpness was observed amongst the reconstructions (p = 0.08). Although ASIR + MBAF2 was non-superior to ASIR regarding overall image quality (p = 0.99), it performed better than FBP (p < 0.001) and MBAF2 (p < 0.001) alone.

Conclusion: The combination of ASIR and MBAF2 resulted in reduced image noise and improved SNR and CNR. The implementation of MBAF2 in clinical practice may result in improved noise reduction performance and could potentiate radiation dose reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.110032DOI Listing
December 2021

Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation.

Clin Cardiol 2021 Nov 19. Epub 2021 Nov 19.

MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

Introduction: There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type.

Methods: AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence.

Results: In total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF.

Conclusion: The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23748DOI Listing
November 2021

Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

Eur Radiol 2021 Nov 16. Epub 2021 Nov 16.

Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, PO BOX 2040, ND-547, 3000-CA, Rotterdam, The Netherlands.

Objectives: To evaluate if routine screening for aortic calcification using unenhanced CT lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (SoC).

Methods: In this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from September 2014 to October 2019 were randomized 1:1 into two groups: SoC alone, including chest radiography, vs. SoC plus preoperative noncontrast CT. The primary endpoint was in-hospital perioperative stroke. Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium. The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect.

Results: A total of 862 patients were evaluated (SoC-group: 433 patients (66 ± 11 years; 74.1% male) vs. SoC + CT-group: 429 patients (66 ± 10 years; 69.9% male)). The perioperative stroke rate (SoC + CT: 2.1%, 9/429 vs. SoC: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (SoC + CT: 4.0% (17/429) vs. SoC: 2.8% (12/433, p = 0.35) did not differ between groups. In-hospital mortality and postoperative delirium were comparable between groups. In the SoC + CT group, aortic calcification was observed on CT in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379).

Conclusions: Preoperative noncontrast CT in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care. Aortic calcification is a frequent finding on the CT scan in these patients but results in major surgical alterations to prevent stroke in only few patients.

Key Points: • Aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery. • Routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care. • No effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-08360-4DOI Listing
November 2021

The aging venous system: from varicosities to vascular cognitive impairment.

Geroscience 2021 Dec 11;43(6):2761-2784. Epub 2021 Nov 11.

Heart and Vascular Center, Semmelweis University, Városmajor Street 68, 1121, Budapest, Hungary.

Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11357-021-00475-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602591PMC
December 2021

Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

N Engl J Med 2021 11;385(20):1845-1855

From the Cardiovascular Division (M.A.P., B.C., S.D.S., K.J., E.B.) and the Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division (E.B.), Brigham and Women's Hospital and Harvard Medical School, Boston; the Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto (E.F.L.), and the Heart Failure and Preventive Cardiology Programs, Department of Veterans Affairs Greater Los Angeles, University of California, Los Angeles, Los Angeles (F.V.M.) - both in California; Duke University Medical Center, Durham, NC (C.B.G.); Rigshospitalet, Blegdamsvej, University of Copenhagen (L.K.), and the Department of Cardiology, Herlev-Gentofte University Hospital (M. Schou) - both in Copenhagen; National Association of Hospital Cardiologists Research Center, Florence (A.P.M.), and the Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo (M. Senni) - both in Italy; Washington University School of Medicine, St. Louis (D.L.M.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M., M.C.P.); Montreal Heart Institute, University of Montreal, Montreal (J.-L.R.); Université de Paris, Assistance Publique-Hôpitaux de Paris, French Alliance for Cardiovascular Trials and INSERM Unité 1148, Paris (P.G.S.); Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo (O.B.); the Department of Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia (M.C.); the Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, SA, Australia (C.G.D.P.); Baylor Soltero CV Research Center, Baylor Scott and White Heart and Vascular Hospital, Dallas (C.E.); Cardiology Service, Sanatorio Modelo Quilmes, Quilmes, Argentina (A.F.); the Department of Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin (U.L.); Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (R.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Acibadem City Clinic Cardiovascular Center, Sofia, Bulgaria (I.P.); National Heart Center Singapore, Singapore (D.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); and Novartis, East Hanover, NJ (M.L., Y.Z., J.G.).

Background: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking.

Methods: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first.

Results: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group.

Conclusions: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2104508DOI Listing
November 2021

Endocrine Management and Hormone Replacement Therapy in Cardiac Donor Management: A Retrospective Observational Study.

Transplant Proc 2021 Dec 30;53(10):2807-2815. Epub 2021 Oct 30.

Department of Anesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary. Electronic address:

Background: Pituitary dysfunction after brainstem death can cause various hormone deficiencies in potential heart donors. The aim of this study was to evaluate the relationship between hormone replacement therapy (HRT; including antidiuretic hormone analog, thyroid hormone, and methylprednisolone) in heart donors and the recipients' outcomes after heart transplantation (HTx).

Methods: We retrospectively analyzed HTxs performed between January 2012 and October 2018. Donor and recipient characteristics were retrieved with a focus on endocrine parameters and HRT. The primary outcome was primary graft dysfunction (PGD). Secondary outcomes were the 30-day and 2-year mortality of the recipients. Univariate and multivariate Cox regression analyses were applied.

Results: The study included 297 HTxs. PGD occurred in 56 recipients (18.9%). In the multivariable Cox analysis, methylprednisolone and thyroxine treatment in donors were associated with a lower odds for PGD (odds ratio [OR], 0.43; 95% CI, 0.19-1.01; P = .052; and OR,: 0.34; 95% CI, 0.15-0.76; P = .009, respectively). In multivariate analysis, thyroxine treatment in donors was associated with a lower odds of PGD (OR, 0.38; 95% CI, 0.17-0.86; P = .020). Donor thyroxine supplementation also had a beneficial effect on recipients' 2-year survival (OR, 0.53; 95% CI, 0.29-0.96; P = .036).

Conclusions: Combined thyroxine and methylprednisolone treatment could be a protective factor against PGD. Thyroxine administration was associated with better 2-year survival in recipients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2021.08.048DOI Listing
December 2021

CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.

Sci Rep 2021 11 1;11(1):21389. Epub 2021 Nov 1.

Institute of Enzymology, Research Centre for Natural Sciences, Magyar tudósok 2, Budapest, 1117, Hungary.

High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients' CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients' CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-00942-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560807PMC
November 2021

Blood-filled cyst of the tricuspid valve: Multiple cardiac disorders, one surgical case.

J Card Surg 2022 Jan 29;37(1):245-248. Epub 2021 Oct 29.

Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

Background: Intracardiac blood cysts are an exceedingly rare occurrence in adulthood. Detailed imaging modalities aid in the diagnosis of such incidental lesions and procedure planning.

Methods: We report the case of a 51-year-old male accusing dyspnea on exertion as a sole symptom which led to the discovery of multiple cardiac anomalies, namely, severe aortic valve insufficiency on a bicuspid aortic valve, ascending aortic aneurysm, a cystic mass on the tricuspid valve, patent foramen ovale, and an occluded right coronary artery.

Results: The disorders were managed in a single surgical intervention, the resected mass being confirmed as a blood cyst.

Conclusions: Our case presents a unique association of cardiac disorders, including a highly uncommon intracardiac blood-filled cyst, and underlines the importance of multimodality imaging and interdisciplinary approach in the successful management of such complex cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.16108DOI Listing
January 2022

Association between affective temperaments and severe coronary artery disease.

J Affect Disord 2021 12 1;295:914-919. Epub 2021 Sep 1.

Department of Family Medicine, Semmelweis University, Budapest, Hungary; Health Service of Zugló (ZESZ), Budapest, Hungary.

Background: Affective temperaments are regarded as subclinical manifestations of major mood disorders and cumulating evidence suggest their role in cardiovascular (CV) pathology. We wished to analyze associations between affective temperaments and severe coronary artery disease (CAD), as assessed by coronary computed tomography angiography (CCTA).

Methods: 225 consecutive patients referred to CCTA due to suspected CAD were included. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). The severity and extent of CAD was evaluated by CCTA. Logistic regression analysis was used to identify predictors of severe CAD (≥70% luminal stenosis in ≥1 major coronary artery).

Results: According to multivariate logistic regression analysis, elevated hyperthymic affective temperament scores significantly decreased the odds of severe CAD (OR=0.92 CI: 0.84-1.00, p = 0.04), while independent positive associations were observed in case of dyslipidemia (OR=4.23 CI: 1.81-9.88, p = 0.001) and cyclothymic affective temperament scores (OR=1.12 CI: 1.02-1.23, p = 0.02). Furthermore, receiver operating curve (ROC) analysis was used to define ideal cutoff values. Hyperthymic temperament scores >11 (OR=0.41 CI: 0.19-0.90, p = 0.03), cyclothymic scores >7 (OR=3.23 CI: 1.35-7.76, p = 0.01) and irritable scores >6 (OR=2.79 CI: 1.17-6.69, p = 0.02) were also independently associated with severe CAD.

Limitations: Our study was limited by the cross-sectional design and the self-report nature of the questionnaires.

Conclusions: Evaluation of affective temperaments might help to identify patients with elevated risk for severe CAD and subsequent need for coronary intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.08.063DOI Listing
December 2021

CAD-RADS may underestimate coronary plaque progression as detected by serial CT angiography.

Eur Heart J Cardiovasc Imaging 2021 Oct 23. Epub 2021 Oct 23.

MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, 68 Városmajor st, 1122 Budapest, Hungary.

Aims: We wished to assess whether different clinical definitions of coronary artery disease (CAD) [segment stenosis and involvement score (SSS, SIS), Coronary Artery Disease-Reporting and Data System (CAD-RADS)] affect which patients are considered to progress and which risk factors affect progression.

Methods And Results: We enrolled 115 subsequent patients (60.1 ± 9.6 years, 27% female) who underwent serial coronary computed tomography angiography (CTA) imaging with >1year between the two examinations. CAD was described using SSS, SIS, and CAD-RADS. Linear mixed models were used to investigate the effects of risk factors on the overall amount of CAD and the effect on annual progression rate of different definitions. Coronary plaque burdens were SSS 4.63 ± 4.06 vs. 5.67 ± 5.10, P < 0.001; SIS 3.43 ± 2.53 vs. 3.89 ± 2.65, P < 0.001; CAD-RADS 0:8.7% vs. 0.0% 1:44.3% vs. 40.9%, 2:34.8% vs. 40.9%, 3:7.0% vs. 9.6% 4:3.5% vs. 6.1% 5:1.7% vs. 2.6%, P < 0.001, at baseline and follow-up, respectively. Overall, 53.0%, 29.6%, and 28.7% of patients progressed over time based on SSS, SIS, and CAD-RADS, respectively. Of the patients who progressed based on SSS, only 54% showed changes in CAD-RADS. Smoking and diabetes increased the annual progression rate of SSS by 0.37/year and 0.38/year, respectively (both P < 0.05). Furthermore, each year increase in age raised SSS by 0.12 [confidence interval (CI) 0.05-0.20, P = 0.001] and SIS 0.10 (CI 0.06-0.15, P < 0.001), while female sex was associated with 2.86 lower SSS (CI -4.52 to -1.20, P < 0.001) and 1.68 SIS values (CI -2.65 to -0.77, P = 0.001).

Conclusion: CAD-RADS could not capture the progression of CAD in almost half of patients with serial CTA. Differences in CAD definitions may lead to significant differences in patients who are considered to progress, and which risk factors are considered to influence progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjci/jeab215DOI Listing
October 2021

Increased Expression of N2BA Titin Corresponds to More Compliant Myofibrils in Athlete's Heart.

Int J Mol Sci 2021 Oct 15;22(20). Epub 2021 Oct 15.

Heart and Vascular Center, Semmelweis University, Városmajor Str. 68., HU-1122 Budapest, Hungary.

Long-term exercise induces physiological cardiac adaptation, a condition referred to as athlete's heart. Exercise tolerance is known to be associated with decreased cardiac passive stiffness. Passive stiffness of the heart muscle is determined by the giant elastic protein titin. The adult cardiac muscle contains two titin isoforms: the more compliant N2BA and the stiffer N2B. Titin-based passive stiffness may be controlled by altering the expression of the different isoforms or via post-translational modifications such as phosphorylation. Currently, there is very limited knowledge about titin's role in cardiac adaptation during long-term exercise. Our aim was to determine the N2BA/N2B ratio and post-translational phosphorylation of titin in the left ventricle and to correlate the changes with the structure and transverse stiffness of cardiac sarcomeres in a rat model of an athlete's heart. The athlete's heart was induced by a 12-week-long swim-based training. In the exercised myocardium the N2BA/N2B ratio was significantly increased, Ser11878 of the PEVK domain was hypophosphorlyated, and the sarcomeric transverse elastic modulus was reduced. Thus, the reduced passive stiffness in the athlete's heart is likely caused by a shift towards the expression of the longer cardiac titin isoform and a phosphorylation-induced softening of the PEVK domain which is manifested in a mechanical rearrangement locally, within the cardiac sarcomere.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms222011110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537917PMC
October 2021
-->