Publications by authors named "Bela Merkely"

546 Publications

Behçet's disease: successful aortic root reconstruction in severely dilated aortoventricular junction after aortic valve replacement with novel surgical method - case report.

J Cardiothorac Surg 2021 Apr 15;16(1):85. Epub 2021 Apr 15.

Semmelweis University, Heart and Vascular Center, Varosmajor 68, Budapest, H-1122, Hungary.

Background: Behçet's disease is an auto-inflammatory disorder categorized as a primer systemic vasculitis of unknown aetiology. Genetic factors, infectious agents and the irregularity of T-cell homeostasis are presumed to be responsible for the emergence of Behçet's disease. Characteristic symptoms are multisystemic. Although cardiovascular involvement is rare, it should be noted due to the difficulty of surgical treatment options.

Case Presentation: Our 44-year-old male patient underwent aortic valve replacement due to aortic regurgitation. At the 15-month follow-up, echocardiography showed detachment of the prosthetic valve and in the aortic root, multiple pseudo-aneurysms were identified. We performed an aortic root reconstruction with a Bentall procedure using a special "skirted" conduit to reduce strain in the suture line between the conduit and the extremely dilated left ventricular outflow tract.

Conclusions: The surgical treatment of cardiovascular manifestations of Behçet's disease remains challenging. This new technique may be beneficial in well-selected cases where the annulus of the aorta is extremely dilated or annular tissue disorder is present.
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http://dx.doi.org/10.1186/s13019-021-01467-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048072PMC
April 2021

New Modalities of 3D Pluripotent Stem Cell-Based Assays in Cardiovascular Toxicity.

Front Pharmacol 2021 29;12:603016. Epub 2021 Mar 29.

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

The substantial progress of the human induced pluripotent stem cell (hiPSC) technologies over the last decade has provided us with new opportunities for cardiovascular drug discovery, regenerative medicine, and disease modeling. The combination of hiPSC with 3D culture techniques offers numerous advantages for generating and studying physiological and pathophysiological cardiac models. Cells grown in 3D can overcome many limitations of 2D cell cultures and animal models. Furthermore, it enables the investigation in an architecturally appropriate, complex cellular environment . Yet, generation and study of cardiac organoids-which may contain versatile cardiovascular cell types differentiated from hiPSC-remain a challenge. The large-scale and high-throughput applications require accurate and standardised models with highly automated processes in culturing, imaging and data collection. Besides the compound spatial structure of organoids, their biological processes also possess different temporal dynamics which require other methods and technologies to detect them. In this review, we summarise the possibilities and challenges of acquiring relevant information from 3D cardiovascular models. We focus on the opportunities during different time-scale processes in dynamic pharmacological experiments and discuss the putative steps toward one-size-fits-all assays.
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http://dx.doi.org/10.3389/fphar.2021.603016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039822PMC
March 2021

Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): Design and Baseline Characteristics.

Eur J Heart Fail 2021 Apr 12. Epub 2021 Apr 12.

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School Boston, MA, USA.

Aims: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven ACE inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial.

Methods And Results: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or LVEF ≤ 40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, eGFR <60ml/min/1.73m , diabetes, prior MI, atrial fibrillation, LVEF <30%, Killip class ≥III, STEMI without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints [cardiovascular (CV) death, HF hospitalization or outpatient development of HF]. Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation MI; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were Killip class ≥2.

Conclusions: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and CV death following AMI.
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http://dx.doi.org/10.1002/ejhf.2191DOI Listing
April 2021

Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans.

Basic Res Cardiol 2021 Apr 12;116(1):24. Epub 2021 Apr 12.

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond Street, 4032, Debrecen, Hungary.

Omecamtiv mecarbil (OM) is a promising novel drug for improving cardiac contractility. We tested the therapeutic range of OM and identified previously unrecognized side effects. The Ca sensitivity of isometric force production (pCa) and force at low Ca levels increased with OM concentration in human permeabilized cardiomyocytes. OM (1 µM) slowed the kinetics of contractions and relaxations and evoked an oscillation between normal and reduced intracellular Ca transients, action potential lengths and contractions in isolated canine cardiomyocytes. Echocardiographic studies and left ventricular pressure-volume analyses demonstrated concentration-dependent improvements in cardiac systolic function at OM concentrations of 600-1200 µg/kg in rats. Administration of OM at a concentration of 1200 µg/kg was associated with hypotension, while doses of 600-1200 µg/kg were associated with the following aspects of diastolic dysfunction: decreases in E/A ratio and the maximal rate of diastolic pressure decrement (dP/dt) and increases in isovolumic relaxation time, left atrial diameter, the isovolumic relaxation constant Tau, left ventricular end-diastolic pressure and the slope of the end-diastolic pressure-volume relationship. Moreover, OM 1200 µg/kg frequently evoked transient electromechanical alternans in the rat in vivo in which normal systoles were followed by smaller contractions (and T-wave amplitudes) without major differences on the QRS complexes. Besides improving systolic function, OM evoked diastolic dysfunction and pulsus alternans. The narrow therapeutic window for OM may necessitate the monitoring of additional clinical safety parameters in clinical application.
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http://dx.doi.org/10.1007/s00395-021-00866-8DOI Listing
April 2021

Significance of extended sports cardiology screening of elite handball referees.

PLoS One 2021 9;16(4):e0249923. Epub 2021 Apr 9.

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

The significance of cardiology screening of referees is not well established. Cardiovascular risk factors and diseases were examined in asymptomatic Hungarian elite handball referees undergoing extended screening: personal/family history, physical examination, 12-lead ECG, laboratory tests, body-composition analysis, echocardiography, and cardiopulmonary exercise testing. Holter-ECG (n = 8), blood pressure monitorization (n = 10), cardiac magnetic resonance imaging (CMR; n = 27) and computer tomography (CCT; n = 4) were also carried out if needed. We examined 100 referees (age: 29.6±7.9years, male: 64, training: 4.3±2.0 hours/week), cardiovascular risk factors were: positive medical history: 24%, overweight: 10%, obesity: 3%, dyslipidaemia: 41%. Elevated resting blood pressure was measured in 38%. Stress-ECG was positive due to ECG-changes in 16%, due to elevated exercise blood pressure in 8%. Echocardiography and/or CMR identified abnormalities in 19%. A significant number of premature ventricular contractions was found on the Holter-ECG in two cases. The CCT showed myocardial bridge or coronary plaques in one-one case. We recommended lifestyle changes in 58%, new/modified antihypertensive or lipid-lowering therapy in 5%, iron-supplementation in 22%. By our results, a high percentage of elite Hungarian handball referees had cardiovascular risk factors or diseases, which, combined with physical and psychological stress, could increase the possibility of cardiovascular events. Our study draws attention to the importance of cardiac screening in elite handball referees.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249923PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034713PMC
April 2021

Balanced Intense Exercise Training Induces Atrial Oxidative Stress Counterbalanced by the Antioxidant System and Atrial Hypertrophy That Is Not Associated with Pathological Remodeling or Arrhythmogenicity.

Antioxidants (Basel) 2021 Mar 15;10(3). Epub 2021 Mar 15.

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

Although regular exercise training is associated with cardiovascular benefits, the increased risk of atrial arrhythmias has been observed after vigorous exercise and has been related to oxidative stress. We aimed at investigating exercise-induced atrial remodeling in a rat model of an athlete's heart and determining sex-specific differences. Age-matched young adult rats were divided into female exercised, female control, male exercised, and male control groups. After exercised animals completed a 12-week-long swim training protocol, echocardiography and in vivo cardiac electrophysiologic investigation were performed. Additionally, atrial histological and gene expression analyses were carried out. Post-mortem atrial weight data and histological examination confirmed marked atrial hypertrophy. We found increased atrial gene expression of antioxidant enzymes along with increased nitro-oxidative stress. No gene expression alteration was found regarding markers of pathological remodeling, apoptotic, proinflammatoric, and profibrotic processes. Exercise training was associated with a prolonged right atrial effective refractory period. We could not induce arrhythmias by programmed stimulation in any groups. We found decreased expression of potassium channels. Female gender was associated with lower profibrotic expression and collagen density. Long-term, balanced exercise training-induced atrial hypertrophy is not associated with harmful electrical remodeling, and no inflammatory or profibrotic response was observed in the atrium of exercised rats.
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http://dx.doi.org/10.3390/antiox10030452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999710PMC
March 2021

Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification.

Medicina (Kaunas) 2021 Mar 9;57(3). Epub 2021 Mar 9.

Medical Imaging Centre, Semmelweis University, 78/A Üllői Street, 1083 Budapest, Hungary.

Background And Objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries' atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet.

Materials And Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries.

Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37-1] and 0.69 [95% CI: 0.38-1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0-0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30-0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42-1].

Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.
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http://dx.doi.org/10.3390/medicina57030252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999274PMC
March 2021

Primary coronary intervention in ST-elevation myocardial infarction

Orv Hetil 2021 03 28;162(13):497-503. Epub 2021 Mar 28.

1 Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika, Budapest, Városmajor u. 68., 1122.

Összefoglaló. Bevezetés: Heveny myocardialis infarctusban a szívizommentés sikere, a beteg életkilátása nagymértékben függ a panasz kezdete és az elzáródott koszorúér rekanalizálása között eltelt ischaemiás időtől. Jelenleg az ér nyitása optimális esetben minden betegnél koszorúér-intervencióval történik. Célkitűzés: Annak vizsgálata, hogy öt év alatt mennyit változtak az ischaemiás idő összetevői, és miben változott az elzáródott ér nyitásának módszere ST-elevációs myocardialis infarctus (STEMI) miatt végzett primer coronariaintervencióban. Módszer: 2014. 01. 01. és 2018. 12. 31. között 1663, STEMI miatt koszorúér-intervencióval kezelt betegnél (1173 férfi és 490 nő) vizsgáltuk évenkénti bontásban a panasztól a koszorúér nyitásáig eltelt idő összetevőit és a 30 napos halálozást. Eredmények: Öt év alatt a panasztól az első egészségügyi kontaktusig medián 2:53 vs. 2:10 óra (p = 0,0132), ettől az intervenciós centrumba történt felvételig medián 1:17 vs. 1:03 óra (p = 0,009), a felvételtől a ballon nyitásáig medián 0:31 vs. 0:29 óra (p = ns) telt el. A panasztól a ballon nyitásáig eltelt idő (medián 5:29 vs. 4:07 óra, p = 0,0001) rövidült, döntően 2014 és 2015 között. A gyógyszerkibocsátó stent beültetése 15%-ról 96%-ra nőtt. A vizsgált években a légzés/keringés támogatás aránya 8,2-10,6-13,9-7,6-8,4, a 30 napos halálozásé 4,1-6,8-11,1-7,4-5,7% volt; a két érték korrelációt mutat (p = 0,827). Következtetés: Öt év alatt a panasztól az első egészségügyi kontaktusig és a kórházi beszállításig eltelt idő rövidült, de az Európai Kardiológiai Társaság ajánlásához képest hosszú; a kórházi felvételtől a ballon nyitásáig eltelt idő megfelelő. A négy órán belüli reperfúzió a betegek közel felében valósult meg. Az intervenciós centrumba való gyorsabb bekerülés javíthatna az eredményen. Orv Hetil. 2021; 162(13): 497-503.

Summary:

Introduction: In acute myocardial infarction, the heart muscle salvage, the patient's life expectancy is highly dependent on the elapsed ischaemic time from the onset of complaint to target vessel recanalisation. Nowadays, target vessel recanalisation is performed with coronary intervention in all patients in optimal case.

Objective: To examine how the components of ischemic time and the opening procedure of the occluded coronary have changed over five years in primary intervention done in acute ST-elevation myocardial infarction (STEMI).

Method: Authors studied data of 1663 (1173 male and 480 female) STEMI patients in annual breakdowns treated with coronary intervention between 01. 01. 2014 and 31. 12. 2018, time from complaint to coronary artery opening, details of intervention and 30 days mortality rate.

Results: During the five years, time intervals were as follows: from onset of complaint to first medical contact: median 2:53 vs. 2:10 hours (p = 0.0132), from this to admission in the interventional centre: median 1:17 vs. 1:03 hours (p = 0.009), from hospital admission to balloon opening: median 0:31 vs. 0:29 hours (p = ns). In total, the complaint to balloon opening time (median 5:29 vs. 4:07 hours, p = 0.0001) diminished, decisively from 2014 to 2015. Ratio of drug-eluting stent implantation increased from 15% to 96%. In the investigated years, the need of respiratory and/or circulatory device support ratio was 8.2-10.6-13.9-7.6-8.4, 30-day mortality rate between 4.1-6.8-11.1-7.4-5.7%; these two values showed a correlation (p = 0.827).

Conclusion: The time from complaint to first medical contact and transfer to hospital against the significant decrease is still longer than the recommendation of the European Society of Cardiology. The time from hospital admission to balloon opening is adequate. Reperfusion within four hours was achieved in half of the patients in total. Faster hospitalization may improve results. Orv Hetil. 2021; 162(13): 497-503.
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http://dx.doi.org/10.1556/650.2021.31907DOI Listing
March 2021

The association between accelerated vascular aging and cyclothymic affective temperament in women.

J Psychosom Res 2021 Mar 17:110423. Epub 2021 Mar 17.

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

Objective: Affective temperaments (depressive, anxious, irritable, hyperthymic, cyclothymic) are regarded as the biologically stable core of personality. Accumulating data suggest their relationship with cardiovascular diseases. However, there are currently limited data on the association of affective temperaments and accelerated vascular aging. The aim of our study was to evaluate the relationship between affective temperaments and vascular age, as assessed by coronary artery calcium scoring (CACS).

Methods: In our cross-sectional study, 209 consecutive patients referred to coronary computed tomography angiography (CCTA) due to suspected coronary artery disease (CAD) were included. All patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) and the Beck Depression Inventory (BDI). Vascular age was estimated using CACS and its difference from chronological age for each patient was calculated. Linear regression analysis was used to identify predictors of accelerated vascular aging in the entire cohort and in male and female sub-populations.

Results: Besides traditional risk factors, cyclothymic temperament score proved to be an independent predictor of accelerated vascular aging in women (β = 0.89 [95%CI: 0.04-1.75]), while this association was absent in men.

Conclusions: Our results suggest that cyclothymic affective temperament is associated with accelerated vascular aging in women. Assessment of affective temperaments may potentiate more precise cardiovascular risk stratification of patients.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110423DOI Listing
March 2021

Partitioning the Right Ventricle Into 15 Segments and Decomposing Its Motion Using 3D Echocardiography-Based Models: The Updated ReVISION Method.

Front Cardiovasc Med 2021 4;8:622118. Epub 2021 Mar 4.

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

Three main mechanisms contribute to global right ventricular (RV) function: longitudinal shortening, radial displacement of the RV free wall (bellows effect), and anteroposterior shortening (as a consequence of left ventricular contraction). Since the importance of these mechanisms may vary in different cardiac conditions, a technology being able to assess their relative influence on the global RV pump function could help to clarify the pathophysiology and the mechanical adaptation of the chamber. Previously, we have introduced our 3D echocardiography (3DE)-based solution-the Right VentrIcular Separate wall motIon quantificatiON (ReVISION) method-for the quantification of the relative contribution of the three aforementioned mechanisms to global RV ejection fraction (EF). Since then, our approach has been applied in several clinical scenarios, and its strengths have been demonstrated in the in-depth characterization of RV mechanical pattern and the prognostication of patients even in the face of maintained RV EF. Recently, various new features have been implemented in our software solution to enable the convenient, standardized, and more comprehensive analysis of RV function. Accordingly, in our current technical paper, we aim to provide a detailed description of the latest version of the ReVISION method with special regards to the volumetric partitioning of the RV and the calculation of longitudinal, circumferential, and area strains using 3DE datasets. We also report the results of the comparison between 3DE- and cardiac magnetic resonance imaging-derived RV parameters, where we found a robust agreement in our advanced 3D metrics between the two modalities. In conclusion, the ReVISION method may provide novel insights into global and also segmental RV function by defining parameters that are potentially more sensitive and predictive compared to conventional echocardiographic measurements in the context of different cardiac diseases.
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http://dx.doi.org/10.3389/fcvm.2021.622118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982839PMC
March 2021

Myocardial work index: a marker of left ventricular contractility in pressure- or volume overload-induced heart failure.

ESC Heart Fail 2021 Mar 23. Epub 2021 Mar 23.

Heart and Vascular Center, Semmelweis University, Városmajor St. 68, Budapest, H-1122, Hungary.

Aims: While global longitudinal strain (GLS) is considered to be a sensitive marker of left ventricular (LV) function, it is significantly influenced by loading conditions. We hypothesized that global myocardial work index (GMWI), a novel marker of LV function, may show better correlation with load-independent markers of LV contractility in rat models of pressure-induced or volume overload-induced heart failure.

Methods And Results: Male Wistar rats underwent either transverse aortic constriction (TAC; n = 12) or aortocaval fistula creation (ACF; n = 12), inducing LV pressure or volume overload, respectively. Sham procedures were performed to establish control groups (n = 12/12). Echocardiographic loops were obtained to determine GLS and GMWI. Pressure-volume analysis with transient occlusion of the inferior caval vein was carried out to calculate preload recruitable stroke work (PRSW), a load-independent 'gold-standard' parameter of LV contractility. Myocardial samples were collected to assess interstitial and perivascular fibrosis area and also myocardial atrial-type natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) relative mRNA expression. Compared with controls, GLS was substantially lower in the TAC group (-7.0 ± 2.8 vs. -14.5 ± 2.5%; P < 0.001) and was only mildly reduced in the ACF group (-13.2 ± 2.4 vs. -15.4 ± 2.0%, P < 0.05). In contrast with these findings, PRSW and GMWI were comparable with sham in TAC (110 ± 26 vs. 116 ± 68 mmHg; 1687 ± 275 mmHg% vs. 1537 ± 662 mmHg%; both P = NS), while it was found to be significantly reduced in ACF (58 ± 14 vs. 111 ± 40 mmHg; 1328 ± 411 vs. 1934 ± 308 mmHg%, both P < 0.01). In the pooled population, GMWI (r = 0.70; P < 0.001) but not GLS (r = -0.23; P = 0.12) showed a strong correlation with PRSW. GLS correlated with interstitial (r = 0.61; P < 0.001) and perivascular fibrosis area (r = 0.54; P < 0.001), and also with myocardial ANP (r = 0.85; P < 0.001) and BNP relative mRNA expression (r = 0.75; P < 0.001), while GMWI demonstrated no or only marginal correlation with these parameters.

Conclusions: Being significantly influenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.
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http://dx.doi.org/10.1002/ehf2.13314DOI Listing
March 2021

Needle in the heart: a rare case of cardiac tamponade caused by a migrated foreign body and mimicking ST segment elevation myocardial infarction.

BMC Cardiovasc Disord 2021 Mar 17;21(1):143. Epub 2021 Mar 17.

Heart and Vascular Center, Semmelweis University, Varosmajor Str. 68, 1122, Budapest, Hungary.

Background: Pericardial tamponade is a serious condition which may eventually lead to severe haemodynamic disturbances and cardiac arrest. It is most often caused by the accumulation of fluid inside the pericardium, as a result of different aetiological factors such as pericarditis, neoplastic diseases, lymphatic dysfunctions, or idiopathic pericardial disease. Pericardial tamponade can develop after cardiac surgical procedures or as a complication of myocardial infarction. Collection of blood inside the pericardial sack can be the result of pericardial or cardiac trauma. It is exceedingly rare for the injury to be caused by a migrating foreign body. Although a typical picture of pericardial tamponade has been previously described, the disorder may clinically resemble an acute myocardial infarction.

Case Presentation: We report the case of a 58-year-old female patient complaining of new onset thoracic pain and shortness of breath. Electrocardiographic examination results were suggestive of an acute inferior myocardial infarction. However, echocardiography revealed significant pericardial tamponade. The cause was found to be a needle which remained inside the pelvis following a previous cesarean delivery, which the patient had undergone 18 years prior. In emergency setting, the needle was removed and the pericardial tamponade was resolved. Due to the prompt and efficient management, the patient had an uneventful postoperative recovery and presented no recurrence at the follow-up examinations.

Conclusions: The migration of foreign bodies through tissues is exceedingly rare. If present, it may cause life-threatening complications. Since the aetiology of pericardial tamponade is vast, a thorough assessment is highly important. Therefore, echocardiography is the imaging modality of choice. We wish to highlight the possibility of migrating foreign bodies as probable cause for pericardial tamponade, as well as the importance of echocardiographic methods in the fast-track evaluation of such critical conditions.
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http://dx.doi.org/10.1186/s12872-021-01950-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972190PMC
March 2021

Posterior Left Atrial Adipose Tissue Attenuation Assessed by Computed Tomography and Recurrence of Atrial Fibrillation After Catheter Ablation.

Circ Arrhythm Electrophysiol 2021 Apr 15;14(4):e009135. Epub 2021 Mar 15.

MTA-SE Cardiovascular Imaging Research Group, Heart & Vascular Center (J.S., L.S., S.H., N.S., L.G., B.M., P.M.-H.), Semmelweis University, Budapest, Hungary.

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCEP.120.009135DOI Listing
April 2021

Sex-Specific Patterns of Mortality Predictors Among Patients Undergoing Cardiac Resynchronization Therapy: A Machine Learning Approach.

Front Cardiovasc Med 2021 25;8:611055. Epub 2021 Feb 25.

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

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fcvm.2021.611055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947699PMC
February 2021

Cardiac and Noncardiac Disease Burden and Treatment Effect of Sacubitril/Valsartan: Insights From a Combined PARAGON-HF and PARADIGM-HF Analysis.

Circ Heart Fail 2021 Mar 12;14(3):e008052. Epub 2021 Mar 12.

Division of Cardiovascular, Brigham and Women's Hospital, Boston, MA (L.E.R., B.L.C., M.A.P., A.S.D., S.D.S.).

Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction.

Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed the previously validated Meta-Analysis Global Group in Chronic Heart Failure risk score into cardiac (left ventricular ejection fraction, New York Heart Association class, blood pressure, time since HF diagnosis, HF medications), noncardiac comorbid (body mass index, creatinine, diabetes, chronic obstructive pulmonary disease, smoking), and demographic (age, gender) categories. Based on these domains, an index representing the balance of cardiac to noncardiac comorbid burden was created (cardiac-comorbid index). Clinical outcomes were time to first HF hospitalization or cardiovascular deaths and all-cause mortality.

Results: Higher scores of the cardiac domain were observed in PARADIGM-HF (10 [7-13] versus 5 [3-6], <0.001) and higher scores of the demographic domain in PARAGON-HF (10 [8-13] versus 5 [2-9], <0.001). In PARADIGM-HF, the contribution of the cardiac domain to clinical outcomes was greater than the noncardiac domain (<0.001), while in PARAGON-HF the attributable risk of the comorbid and demographic categories predominated. Individual scores from each sub-domain were linearly associated with the risk of clinical outcomes (<0.001). Beneficial effects of sacubitril/valsartan were observed in patients with preponderance of cardiac over noncardiac comorbid burden (cardiac-comorbid index >5 points), suggesting a significant treatment effect modification (interaction <0.05 for both outcomes).

Conclusions: Domains of disease burden are clinically relevant features that influence the prognosis and treatment of patients with HF. The therapeutic benefits of sacubitril/valsartan vary according to the balance of components of disease burden, across different ranges of left ventricular ejection fraction.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008052DOI Listing
March 2021

Orientation of the right superior pulmonary vein affects outcome after pulmonary vein isolation.

Eur Heart J Cardiovasc Imaging 2021 Mar 10. Epub 2021 Mar 10.

Heart and Vascular Center, Semmelweis University, 68 Varosmajor Street, 1122 Budapest, Hungary.

Aims: Controversial results have been published regarding the influence of pulmonary vein (PV) anatomical variations on outcomes after pulmonary vein isolation (PVI). However, no data are available on the impact of PV orientation on the long-term success rates of point-by-point PVI. We sought to determine the impact of PV anatomy and orientation on atrial fibrillation (AF)-free survival in patients undergoing PVI using the radiofrequency point-by-point technique.

Methods And Results: We retrospectively included 448 patients who underwent initial point-by-point radiofrequency ablation for AF at our department. Left atrial computed tomography angiography was performed before each procedure. PV anatomical variations, ostial parameters (area, effective diameter, and eccentricity), orientation, and their associations with 24-month AF-free survival were analysed. PV anatomical variations and ostial parameters were not predictive for AF-free survival (all P > 0.05). Univariate analysis showed that female sex (P = 0.025) was associated with higher rates of AF recurrence, ventral-caudal (P = 0.002), dorsal-cranial (P = 0.034), and dorsal-caudal (P = 0.042) orientation of the right superior PV (RSPV), on the other hand, showed an association with lower rates of AF recurrence, when compared with the reference ventral-cranial orientation. On multivariate analysis, both female sex [odds ratio (OR) 1.83, 95% CI 1.15-2.93, P = 0.011] and ventral-caudal RSPV orientation, compared with ventral-cranial orientation, proved to be independent predictors of 24-month AF recurrence (OR 0.37, 95% CI 0.19-0.71, P = 0.003).

Conclusion: Female sex and ventral-caudal RSPV orientation have an impact on long-term arrhythmia-free survival. Assessment of PV orientation may be a useful tool in predicting AF-free survival and may contribute to a more personalized management of AF.
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http://dx.doi.org/10.1093/ehjci/jeab041DOI Listing
March 2021

Geometrical remodeling of the mitral and tricuspid annuli in response to exercise training: a 3D echocardiographic study in elite athletes.

Am J Physiol Heart Circ Physiol 2021 Mar 5. Epub 2021 Mar 5.

Semmelweis University Heart and Vascular Center, Budapest, Hungary.

Intense exercise exposes the heart to significant hemodynamic demands, resulting in adaptive changes in cardiac morphology and function. Nevertheless, the athletic adaptation of the atrioventricular valves remains to be elucidated. Our study aimed to characterize the geometry of mitral (MA) and tricuspid (TA) annuli in elite athletes using 3D echocardiography. Thirty-four athletes presented with functional mitral regurgitation (FMR) were retrospectively identified and compared to 34 athletes without MR, and 34 healthy, sedentary volunteers. 3DE datasets were used to quantify MA and TA geometry and leaflet tenting by dedicated softwares. MA and TA areas, as well as tenting volumes, were higher in athletes compared to controls. MA area was significantly higher in athletes with MR compared to those without (8.2±1.0 vs. 7.2±1.0cm/m, p<0.05). Interestingly, athletes with MR also presented with a significantly higher TA area (7.2±1.1 vs. 6.5±1.1cm/m, p<0.05). Non-planar angle describing the MA's saddle shape was less obtuse in athletes without MR, whereas the values of athletes with MR were comparable to controls. The exercise-induced relative increases in left ventricular (35±25%) and left atrial (40±29%) volumes were similar; however, the increment in the MA area was disproportionately higher (63±23%, overall p<0.001). The relative increase in TA area (40±23%) was also higher compared to the increment in right ventricular volume (34±25%, p<0.05). Atrioventricular annuli undergo a disproportionate remodeling in response to regular exercise. Athletic adaptation is characterized by both annular enlargement and increased leaflet tenting of both valves. There are differences in MA geometry in athletes presented with versus without FMR.
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http://dx.doi.org/10.1152/ajpheart.00877.2020DOI Listing
March 2021

Atrial Fibrillation Burden and Clinical Outcomes in Heart Failure: The CASTLE-AF Trial.

JACC Clin Electrophysiol 2021 Feb 19. Epub 2021 Feb 19.

Cardiac Electrophysiology, Tulane University School of Medicine, New Orleans, Louisiana, USA. Electronic address:

Objectives: This subanalysis of the CASTLE-AF trial (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) aimed to address the association between atrial fibrillation (AF) recurrence, AF burden, and hard clinical outcomes in heart failure (HF) patients with AF.

Background: The CASTLE-AF trial demonstrated the benefit of CA compared to pharmacological treatment in decreasing mortality and CV hospitalizations in patients with AF and HFrEF. However, the impact of AF recurrence and AF burden after ablation on long-term treatment benefit remains unknown.

Methods: The CASTLE-AF protocol randomized 363 patients with coexisting HF and AF in a multicenter prospective controlled fashion to catheter ablation (n = 179) versus pharmacological therapy (n = 184). Two hundred eighty patients were included in this subanalysis (as-treated), 128 of them underwent ablation and 152 received pharmacological treatment. All patients had implanted dual chamber or biventricular implantable defibrillators with activated home monitoring capabilities. The individual AF burden was calculated as the percentage of the atrial arrhythmia time per day.

Results: AF burden at baseline was not predictive of the primary endpoint (p = 0.473) or all-cause mortality (p = 0.446). AF recurrence (defined as any episode >30 s) did not show any relationship with the primary endpoints of mortality and occurrence of HF, irrespective of the treatment arm. An AF burden below 50% after 6 months of catheter ablation, was associated with a significant decrease in primary composite outcome (hazard ratio: 0.33, 95% confidence interval: 0.15 to 0.71; p = 0.014) and all-cause mortality (hazard ratio: 0.23, 95% confidence interval: 0.07 to 0.71; p = 0.031). The risk of the primary endpoint or mortality was directly related to a low (<50%) or high (≥50%) AF burden at 6 months post-ablation.

Conclusions: AF burden at 6 months was predictive of hard clinical outcomes in HF patients with AF. The first recurrent atrial tachyarrhythmia episode >30 s after ablation was not associated with improvement in mortality and hospitalization for HF. (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF [CASTLE-AF]; NCT00643188).
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http://dx.doi.org/10.1016/j.jacep.2020.11.021DOI Listing
February 2021

The First 5 Years of the Newest Eurotransplant Member State: Hungarian Results of International Organ Exchange From 2014 to 2018.

Transplant Proc 2021 Feb 24. Epub 2021 Feb 24.

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

Introduction: Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible.

Method: A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges.

Result: The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96.

Conclusion: Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors.
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http://dx.doi.org/10.1016/j.transproceed.2021.01.042DOI Listing
February 2021

Acute heart transplantation from mechanical circulatory support in a human immunodeficiency virus-positive patient with fulminant myocarditis.

ESC Heart Fail 2021 Apr 25;8(2):1643-1648. Epub 2021 Feb 25.

Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary.

Since the establishment of highly active antiretroviral therapy, survival rates have improved among patients with human immunodeficiency virus infection giving them the possibility to become transplant candidates. Recent publications revealed that human immunodeficiency virus-positive heart transplant recipients' survival is similar to non-infected patients. We present the case of a 40-year-old human immunodeficiency virus infected patient, who was hospitalized due to severely decreased left ventricular function with a possible aetiology of acute myocarditis, that has later been confirmed by histological investigation of myocardial biopsy. Due to rapid progression to refractory cardiogenic shock, extracorporeal membrane oxygenation implantation had been initiated, which was upgraded to biventricular assist device later. On the 35th day of upgraded support, the patient underwent heart transplantation uneventfully. Our clinical experience confirms that implementation of temporary mechanical circulatory support and subsequent cardiac transplantation might be successful in human immunodeficiency virus-positive patients even in case of new onset, irreversible acute heart failure.
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http://dx.doi.org/10.1002/ehf2.13271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006693PMC
April 2021

Superficial temporal artery access for percutaneous coronary artery stenting during the COVID-19 pandemic: a case report.

Eur Heart J Case Rep 2021 Feb 27;5(2):ytaa520. Epub 2020 Dec 27.

Bács-Kiskun County Hospital, Teaching Hospital of the Albert Szent-Györgyi Medical School, University of Szeged, Kecskemét, Invasive Cardiology, 6000, Nyíri Street 38, Hungary.

Background: The COVID-19 pandemic creates new challenges for healthcare, including invasive cardiology.

Case Summary: We discuss the case of a 65-year-old man who presented with non-ST segment elevation myocardial infarction combined with bilateral pneumonia. The patient had known severe iliac artery lesions with prior interventions and bilateral subclavian artery occlusions. After unsuccessful femoral artery access, the diagnostic angiography and the right coronary artery percutaneous coronary intervention were successfully performed from ultrasound-guided lower superficial temporal artery access.

Discussion: We showed that superficial temporal access can be used as an alternate access site for diagnostic coronary angiography and intervention when standard wrist and femoral access sites are not readily accessible.
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http://dx.doi.org/10.1093/ehjcr/ytaa520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799199PMC
February 2021

Changes in strain parameters at different deterioration levels of left ventricular function: A cardiac magnetic resonance feature-tracking study of patients with left ventricular noncompaction.

Int J Cardiol 2021 May 9;331:124-130. Epub 2021 Feb 9.

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

Background: There is a lack of cardiac MRI information on left ventricular (LV) strain and rotational parameters of left ventricular noncompaction (LVNC) patients with reduced ejection fraction (EF). Thus, we sought to use feature tracking (FT) to describe these changes at different levels of EF deterioration.

Methods: We included 31 adult LVNC patients with reduced LV EF (Group B, EF < 50%) without any comorbidities or concomitant cardiac diseases, 31 age- and sex-matched LVNC patients with good EF (Group A, EF > 50%) and 31 healthy controls. Group B was divided according to LV EF into two subgroups (Group B-1: EF 35-50%, Group B-2: EF < 35%). Their global longitudinal, circumferential (GCS), and radial (GRS) strains; LV segmental strains; LV apical and basal rotation values; and patterns and degree of LV dyssynchrony were measured.

Results: All of the global and mean segmental strain parameters were significantly worse in Groups B, B-1 and B-2 than in Group A and in the controls. The LV mechanical dispersion increased as LV EF decreased. The degree of apical rotation was the highest in the control group, almost the same in Group A and the lowest and in the reverse direction in Group B-2. A rotational pattern, clockwise-directed rigid body rotation (RBR), was found in 39% of the Group B patients, and a counterclockwise-directed RBR was found in 26% of the Group A patients.

Conclusions: The strain values and rotational parameters changed as the EF decreased. These changes affected the global LV, and we did not identify an LVNC-specific strain pattern.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.072DOI Listing
May 2021

Similar outcomes with manual contact force ablation catheters and traditional catheters in the treatment of outflow tract premature ventricular complexes.

Europace 2021 Apr;23(4):596-602

Department of Cardiology, Semmelweis University Heart and Vascular Centre, Városmajor Street 68, H-1122 Budapest, Hungary.

Aims: Unlike in atrial fibrillation ablation, there is a lack of appropriately sized and properly designed studies regarding outflow tract (OT) premature ventricular complex (PVC) ablation outcomes with contact force sensing (CFS) catheters. We aimed to compare the acute success-, complication-, and long-term recurrence rates of manual CFS catheters with traditional irrigated catheters (T) in OT PVC ablation.

Methods And Results: Single-centre, propensity-matched data of 75-75 patients ablated for right-sided OT (RVOT) or left-sided OT (LVOT) PVCs in 2015-17 with CFS or T catheters were compared. Acute success rate, peri-procedural complications, post-procedural daily PVC burden, and long-term recurrence rates were compared on intention-to-treat basis. Acute success rate equalled 80% in both groups, with no difference in force values in the CFS group comparing successful or failed cases [12.0 (8.75-17.0) vs. 16.0 (10.25-22.25) g, P = 0.21]. There were three cases of pseudo-aneurysm and one cardiac tamponade. PVC burden fell significantly from baseline 22 (15-30)% to 2 (0-10)% (P < 0.0001), with no difference between catheter types [CFS: 1 (0-7)% vs. T: 4 (1-12) %; P = 0.21]. There was no significant difference in recurrence-free survival of CFS and T catheters (58 vs. 59%, P = 0.29) during 12 months of follow-up, respectively. Recurrence in the CFS group did not differ either by the force exerted below or above the median value of 12 g (P = 0.66).

Conclusion: Both types of catheters can effectively reduce OT PVC burden with minimal serious complication rates. Ablation with CFS or T catheters gives similar acute- and long-term results.
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http://dx.doi.org/10.1093/europace/euaa393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025084PMC
April 2021

Prognostic significance of cardiac magnetic resonance-based markers in patients with hypertrophic cardiomyopathy.

Int J Cardiovasc Imaging 2021 Feb 8. Epub 2021 Feb 8.

Heart and Vascular Center, Semmelweis University, 68 Varosmajor St, Budapest, 1122, Hungary.

The prognosis of patients with hypertrophic cardiomyopathy (HCM) varies greatly. Cardiac magnetic resonance (CMR) is the gold standard method for assessing left ventricular (LV) mass and volumes. Myocardial fibrosis can be noninvasively detected using CMR. Moreover, feature-tracking (FT) strain analysis provides information about LV deformation. We aimed to investigate the prognostic significance of standard CMR parameters, myocardial fibrosis, and LV strain parameters in HCM patients. We investigated 187 HCM patients who underwent CMR with late gadolinium enhancement and were followed up. LV mass (LVM) was evaluated with the exclusion and inclusion of the trabeculae and papillary muscles (TPM). Global LV strain parameters and mechanical dispersion (MD) were calculated. Myocardial fibrosis was quantified. The combined endpoint of our study was all-cause mortality, heart transplantation, malignant ventricular arrhythmias and appropriate implantable cardioverter defibrillator (ICD) therapy. The arrhythmia endpoint was malignant ventricular arrhythmias and appropriate ICD therapy. The LVM index (LVMi) was an independent CMR predictor of the combined endpoint independent of the quantification method (p < 0.01). The univariate predictors of the combined endpoint were LVMi, global longitudinal (GLS) and radial strain and longitudinal MD (MDL). The univariate predictors of arrhythmia events included LVMi and myocardial fibrosis. More pronounced LV hypertrophy was associated with impaired GLS and increased MDL. More extensive myocardial fibrosis correlated with impaired GLS (p < 0.001). LVMi was an independent CMR predictor of major events, and myocardial fibrosis predicted arrhythmia events in HCM patients. FT strain analysis provided additional information for risk stratification in HCM patients.
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http://dx.doi.org/10.1007/s10554-021-02165-8DOI Listing
February 2021

Nocturnal respiratory rate predicts ICD benefit: A prospective, controlled, multicentre cohort study.

EClinicalMedicine 2021 Jan 21;31:100695. Epub 2020 Dec 21.

Klinikum rechts der Isar, Medizinische Klinik und Poliklinik I, Technical University of Munich, Munich, Germany.

Background: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations.

Methods: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419).

Findings: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect ( = 0.0070). While the 1,316 patients with NRR<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376-0.746);  = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669-1.438);  = 0.9202).

Interpretation: In the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially.

Funding: European Community's 7th Framework Programme FP7/2007-2013 (602299).
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http://dx.doi.org/10.1016/j.eclinm.2020.100695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846675PMC
January 2021

Sodium-glucose cotransporter 2 inhibitors reduce myocardial infarct size in preclinical animal models of myocardial ischaemia-reperfusion injury: a meta-analysis.

Diabetologia 2021 Apr 23;64(4):737-748. Epub 2021 Jan 23.

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

Aims/hypothesis: Large cardiovascular outcome trials demonstrated that the cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors might reach beyond glucose-lowering action. In this meta-analysis, we sought to evaluate the potential infarct size-modulating effect of SGLT2 inhibitors in preclinical studies.

Methods: In this preregistered meta-analysis (PROSPERO: CRD42020189124), we included placebo-controlled, interventional studies of small and large animal models of myocardial ischaemia-reperfusion injury, testing the effect of SGLT2 inhibitor treatment on myocardial infarct size (percentage of area at risk or total area). Standardised mean differences (SMDs) were calculated and pooled using random-effects method. We evaluated heterogeneity by computing Τ and I values. Meta-regression was performed to explore prespecified subgroup differences according to experimental protocols and their contribution to heterogeneity was assessed (pseudo-R values).

Results: We identified ten eligible publications, reporting 16 independent controlled comparisons on a total of 224 animals. Treatment with SGLT2 inhibitor significantly reduced myocardial infarct size compared with placebo (SMD = -1.30 [95% CI -1.79, -0.81], p < 0.00001), referring to a 33% [95% CI 20%, 47%] difference. Heterogeneity was moderate (Τ = 0.58, I = 60%). SGLT2 inhibitors were only effective when administered to the intact organ system, but not to isolated hearts (p interaction <0.001, adjusted pseudo-R = 47%). While acute administration significantly reduced infarct size, chronic treatment was superior (p interaction <0.001, adjusted pseudo-R = 85%). The medications significantly reduced infarct size in both diabetic and non-diabetic animals, favouring the former (p interaction = 0.030, adjusted pseudo-R = 12%). Treatment was equally effective in rats and mice, as well as in a porcine model. Individual study quality scores were not related to effect estimates (p = 0.33). The overall effect estimate remained large even after adjusting for severe forms of publication bias.

Conclusions/interpretation: The glucose-lowering SGLT2 inhibitors reduce myocardial infarct size in animal models independent of diabetes. Future in vivo studies should focus on clinical translation by exploring whether SGLT2 inhibitors limit infarct size in animals with relevant comorbidities, on top of loading doses of antiplatelet agents. Mechanistic studies should elucidate the potential relationship between the infarct size-lowering effect of SGLT2 inhibitors and the intact organ system.
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http://dx.doi.org/10.1007/s00125-020-05359-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940278PMC
April 2021

The effect of cognitive dysfunction on mid- and long-term mortality after vascular surgery.

BMC Geriatr 2021 Jan 13;21(1):46. Epub 2021 Jan 13.

Department of Anesthesiology and Intensive Therapy, Semmelweis University, 78 Üllői st., Budapest, H-1082, Hungary.

Background: In recent decades, previous studies have noted the importance of frailty, which is a frequently used term in perioperative risk evaluations. Psychological and socioeconomical domains were investigated as part of frailty syndrome. The aim of this study was to assess the importance of these factors in mortality after vascular surgery.

Methods: In our prospective, observational study (ClinicalTrials.gov Identifier: NCT02224222), we examined 164 patients who underwent elective vascular surgery between 2014 and 2017. At the outpatient anaesthesiology clinic, patients completed a questionnaire about cognitive functions, depression and anxiety, social support and self-reported quality of life were assessed using a comprehensive frailty index, in addition to medical variables. Propensity score matching was performed to analyse the difference between patients and controls in a nationwide population cohort. The primary outcome was 4 year mortality. The Kaplan-Meier method and Cox regression analysis were used for statistical analyses.

Results: The patients' mean age was 67.05 years (SD: 9.49 years). Mini-Mental State Examination scores of less than 27 points were recorded for 41 patients. Overall mortality rates were 22.4 and 47.6% in the control and cognitive impairment groups, respectively (p = 0.013). In the univariate Cox regression analysis, cognitive impairment measured using age- and education-adjusted MMSE scores increased the risk of mortality (AHR: 2.842, 95% CI: 1.389-5.815, p = 0.004).

Conclusion: Even mild cognitive dysfunction measured preoperatively using the MMSE represents a potentially important risk factor for mortality after vascular surgery.
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http://dx.doi.org/10.1186/s12877-020-01994-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805183PMC
January 2021

Impact of periprocedural morphine use on mortality in STEMI patients treated with primary PCI.

PLoS One 2021 13;16(1):e0245433. Epub 2021 Jan 13.

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

Background: Intravenous morphine (MO) decreases the effect of all oral platelet P2Y12 receptor inhibitors in vitro and observational reports suggest that its use may be associated with larger infarct size. Yet, there are limited data available about the impact of this interaction on clinical outcomes. We studied the effect of MO on mortality in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI using a prospective registry.

Methods: Of the 1255 patients who underwent primary PCI, 397 received MO based on physician's judgment. Clopidogrel was used as P2Y12 receptor antagonist in all cases. Median follow-up time was 7.5 years with 457 deaths. To adjust for confounding, two propensity score-based procedures were performed: 1 to 1 matching (PSM, 728 cases), and inverse probability of treatment weighting (IPTW) retaining data from all patients. Primary outcome measure was time to all-cause death, whereas predischarge left ventricular ejection fraction (LVEF) was used as secondary end point.

Results: An adequate balance on baseline covariates was achieved by both methods. We found no difference in survival as the HR (MO/no MO) was 0.98 (95% confidence interval [CI]: 0.76-1.26), p = 0.86 using PSM and 1.01 (95% CI: 0.84-1.23), p = 0.88 with IPTW. Likewise, distributions of LVEFs were similar using either methods: with PSM, median LVEFs were 50.0% (interquartile range [IQR]: 43.0%-55.3%) vs 50.0% (IQR: 42.0%-55.0%) in the no MO and MO groups, respectively (p = 0.76), whereas using IPTW, they were 50.0% (IQR: 42.5%-55.0%) vs 50.0% (IQR: 41.0%-55.0%), respectively (p = 0.86).

Conclusions: Our data suggest that morphine use may have no impact on long-term mortality and on predischarge ejection fraction in STEMI patients treated with primary PCI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245433PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806148PMC
January 2021

Atrio-esophageal fistula clinically presented as pericardial-esophageal fistula.

J Interv Card Electrophysiol 2021 Jan 12. Epub 2021 Jan 12.

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

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http://dx.doi.org/10.1007/s10840-020-00922-8DOI Listing
January 2021