Decreased level of serum NT-proCNP associates with disease severity in COVID-19.

BACKGROUND: C-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the current study, we aimed to determine possible changes in the NT-proCNP levels of patients with coronavirus disease 2019 (COVID-19), with special regard to disease severity and outcome. METHODS: In this retrospective analysis, we determined the serum level of NT-proCNP in hospitalized patients with symptoms of upper respiratory tract infection, using their blood samples taken on admission, stored in a biobank. The NT-proCNP levels of 32 SARS-CoV-2 positive and 35 SARS-CoV-2 negative patients were measured to investigate possible correlation with disease outcome. SARS-CoV-2 positive patients were then divided into two groups based on their need for intensive care unit treatment (severe and mild COVID-19). RESULTS: The NT-proCNP was significantly different in the study groups (e.g. severe and mild COVID-19 and non-COVID-19 patients), but showed inverse changes compared to previous observations in septic patients: lowest levels were detected in critically ill COVID-19 patients, while highest levels in the non-COVID-19 group. A low level of NT-proCNP on admission was significantly associated with severe disease outcome. CONCLUSIONS: Low-level NT-proCNP on hospital admission is associated with a severe COVID-19 disease course. The pathomechanism underlying this observation remains to be elucidated, while future studies in larger patient cohorts are necessary to confirm these observations and reveal therapeutic importance. Trial registration DRKS00026655 Registered 26. November 2021.

Three-dimensional transesophageal echocardiographic evaluation of pulmonary vein anatomy prior to cryoablation: validation with cardiac CT scan.

BACKGROUND: Anatomical characteristics of the left atrium and the pulmonary veins (PVs) may be relevant to the success rate of cryoballoon (CB)-ablation for atrial fibrillation (AF). Cardiac computed tomography (CCT) is considered as the gold standard for preablation imaging. Recently, three-dimensional transesophageal echocardiography (3DTOE) has been proposed for preprocedural assessment of cardiac structures relevant to CB-ablation. The accuracy of 3DTOE has not been validated by other imaging modalities. OBJECTIVE: We prospectively evaluated the feasibility and the accuracy of 3DTOE imaging for the assessment of left atrial and PV structures prior to pulmonary vein isolation (PVI). In addition, CCT was used to validate the measurements obtained with 3DTOE. METHODS: PV anatomy of 67 patients (59.7% men, mean age 58.5 ± 10.5 years) was assessed using both 3DTOE and CCT scan prior to PVI with the Arctic Front CB. The following parameters were measured bilaterally: PV ostium area (OA), the major and minor axis diameters of the ostium (a > b) and the width of the carina between the superior and the inferior PVs. In addition, the width of the left lateral ridge (LLR) between the left atrial appendage and the left superior PV. Evaluation of inter-technique agreement was based on linear regression with Pearson correlation coefficient (PCC) and Bland-Altman analysis of biases and limits of agreement. RESULTS: Moderate positive correlation (PCC 0.5-0.7) was demonstrated between the two imaging methods for the right superior PV's OA and both axis diameters, the width of the LLR and left superior PV (LSPV) minor axis diameter (b) with limits of agreement ˂50% and no significant biases. Low positive or negligible correlation (PCC < 0.5) was found for both inferior PV parameters. CONCLUSIONS: Detailed assessment of the right superior PV parameters, LLR and LSPV b is feasible with 3DTOE prior to AF ablation. This 3DTOE measurements demonstrated a clinically acceptable inter-technique agreement with those obtained with CCT.

The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications.

Recent cardiotropic drug developments have focused on cardiac myofilaments. Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). Here, we analyzed the inotropic effects of danicamtiv in detail. To this end, changes in sarcomere length and intracellular Ca2+ levels were monitored in parallel, in enzymatically isolated canine cardiomyocytes, and detailed echocardiographic examinations were performed in anesthetized rats in the absence or presence of danicamtiv. The systolic and diastolic sarcomere lengths decreased; contraction and relaxation kinetics slowed down with increasing danicamtiv concentrations without changes in intracellular Ca2+ transients in vitro. Danicamtiv evoked remarkable increases in left ventricular ejection fraction and fractional shortening, also reflected by changes in systolic strain. Nevertheless, the systolic ejection time was significantly prolonged, the ratio of diastolic to systolic duration was reduced, and signs of diastolic dysfunction were also observed upon danicamtiv treatment in vivo. Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations.

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

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 Ca2+ sensitivity of isometric force production (pCa50) and force at low Ca2+ 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 Ca2+ 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/dtmin) 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.

Predictors of Hospital Mortality in Patients with Acute Coronary Syndrome Complicated by Cardiogenic Shock.

As demonstrated by earlier studies, pre-hospital triage with trans-telephonic electrocardiogram (TTECG) and direct referral for catheter therapy shows great value in the management of out-of-hospital chest pain emergencies. It does not only improve in-hospital mortality in ST-segment elevation myocardial infarction, but it has also been identified as an independent predictor of higher in-hospital survival rate. Since TTECG-facilitated triage shortens both transport time and percutaneous coronary intervention (PCI)-related procedural time intervals, it was hypothesized that even high-risk patients with acute coronary syndrome (ACS) and cardiogenic shock (CS) might also benefit from TTECG-based triage. Here, we decided to examine our database for new triage- and left ventricular (LV) function-related parameters that can influence in-hospital mortality in ACS complicated by CS. ACS patients were divided into two groups, namely, (1) hospital death patients (n = 77), and (2) hospital survivors (control, n = 210). Interestingly, TTECG-based consultation and triage of CS and ACS patients were confirmed as significant independent predictors of lower hospital mortality risk (odds ratio (OR) 0.40, confidence interval (CI) 0.21-0.76, p = 0.0049). Regarding LV function and blood chemistry, a good myocardial reperfusion after PCI (high area at risk (AAR) blush score/AAR LV segment number; OR 0.85, CI 0.78-0.98, p = 0.0178) and high glomerular filtration rate (GFR) value at the time of hospital admission (OR 0.97, CI 0.96-0.99, p = 0.0042) were the most crucial independent predictors of a decreased risk of in-hospital mortality in this model. At the same time, a prolonged time interval between symptom onset and hospital admission, successful resuscitation, and higher peak creatine kinase activity were the most important independent predictors for an increased risk of in-hospital mortality. In ACS patients with CS, (1) an early TTECG-based teleconsultation and triage, as well as (2) good myocardial perfusion after PCI and a high GFR value at the time of hospital admission, appear as major independent predictors of a lower in-hospital mortality rate.

Prophylactic, single-drug cardioprotection in a comparative, experimental study of doxorubicin-induced cardiomyopathy.

BACKGROUND: Cardiomyopathy is a common side effect of doxorubicin (DOX) chemotherapy. Despite intensive research efforts in the field, there is still no evidence available for routine cardioprotective prophylaxis to prevent cardiotoxicity in the majority of oncological patients at low risk of cardiovascular disease. We have recently demonstrated the advantages of a prophylactic, combined heart failure therapy in an experimental model of DOX-induced cardiomyopathy. In the current work, we focus on individually applied prophylactic medications studied in the same translational environment to clarify their distinct roles in the prevention of DOX cardiotoxicity. METHODS: Twelve-week-old male Wistar rats were divided into 5 subgroups. Prophylactic ß-blocker (BB, bisoprolol), angiotensin-converting enzyme inhibitor (ACEI, perindopril) or aldosterone antagonist (AA, eplerenone) treatments were applied 1 week before DOX administration, then 6 cycles of intravenous DOX chemotherapy were administered. Rats receiving only intravenous DOX or saline served as positive and negative controls. Blood pressure, heart rate, body weight, and echocardiographic parameters were monitored in vivo. Two months after the last DOX administration, the animals were sacrificed, and their heart and serum samples were frozen in liquid nitrogen for histological, mechanical, and biochemical measurements. RESULTS: All prophylactic treatments increased the survival of DOX-receiving animals. The lowest mortality rates were seen in the BB and ACEI groups. The left ventricular ejection fraction was only preserved in the BB group. The DOX-induced increase in the isovolumetric relaxation time could not be prevented by any prophylactic treatment. A decreased number of apoptotic nuclei and a preserved myocardial ultrastructure were found in all groups receiving prophylactic cardioprotection, while the DOX-induced fibrotic remodelling and the increase in caspase-3 levels could only be substantially prevented by the BB and ACEI treatments. CONCLUSION: Primary prophylaxis with cardioprotective agents like BB or ACEI has a key role in the prevention of DOX-induced cardiotoxicity in healthy rats. Future human studies are necessary to implement this finding in the clinical management of oncological patients free of cardiovascular risk factors.

Paroxysmal and persistent atrial fibrillation ablation outcomes with the pulmonary vein ablation catheter GOLD duty-cycled phased radiofrequency ablation catheter: quality of life and 12-month efficacy results from the GOLD Atrial Fibrillation Registry.

AIMS: The GOLD AF Registry has been designed to prospectively assess the population, indications, and outcomes using second-generation phased radiofrequency (RF) ablation (pulmonary vein ablation catheter GOLD) in a global examination of standard-of-care use for the treatment of paroxysmal and persistent atrial fibrillation (AF). METHODS AND RESULTS: GOLD AF (NCT02433613) is a prospective, observational, multi-centre registry designed to characterize efficacy and safety of phased RF ablation in patients with AF. The primary endpoint was freedom from AF recurrence at 12-month follow-up after a 90-day blanking period. Ancillary objectives include safety, procedural efficiency, and quality of life (QoL). The QoL assessment using the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and the European Heart Rhythm Association (EHRA) Score of AF-related symptoms was collected at baseline and 12 months. In total, 1054 patients were included in this analysis (age 60.6, 67.6% male, 26.5% PersAF). Kaplan-Meier estimate of freedom from AF recurrence was 77.7% at 12 months. Peri-procedural device or procedure-related complications were observed in 26 (2.5%) patients, with a low stroke rate of 0.3%. One-year post-ablation, the EHRA AF Symptom score decreased in 68% of patients. The AFEQT score improvement was observed in 88.4% and 90.4% of patients who completed the questionnaire in-person or interviewed by phone at 12 month follow-up, respectively. CONCLUSION: Phased RF ablation for the treatment of paroxysmal and persistent AF demonstrated a 77.7% freedom from AF recurrence at 12 months in addition to a significant reduction in arrhythmia symptoms and clinically meaningful improved QoL. Low peri-procedural complication rate of <3% was reported.

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome.

BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, diastolic dysfunction, tachycardia, heart failure, and atrial fibrillation, and it can alleviate cardiotoxicity. BGP-15 exhibits chemoprotective properties in different cytostatic therapies, and has also proven to be photoprotective. It can additionally have advantageous effects in mitochondrial-stress-related diseases. Although the precise mechanism of the effect is still unknown to us, we know that the molecule is a PARP inhibitor, chaperone co-inducer, reduces ROS production, and is able to remodel the organization of cholesterol-rich membrane domains. In the following review, our aim was to summarize the investigated molecular mechanisms and pharmacological effects of this potential API. The main objective was to present the wide pharmacological potentials of this chemical agent.

Advantages of prophylactic versus conventionally scheduled heart failure therapy in an experimental model of doxorubicin-induced cardiomyopathy.

BACKGROUND: Chemotherapy-induced left ventricular dysfunction represents a major clinical problem, which is often only recognised at an advanced stage, when supportive therapy is ineffective. Although an early heart failure treatment could positively influence the health status and clinical outcome, there is still no evidence of routine prophylactic cardioprotection for the majority of patients without previous cardiovascular history awaiting potentially cardiotoxic chemotherapy. In this study, we set out to investigate whether a prophylactic cardioprotective therapy relative to a conventionally scheduled heart failure treatment is more effective in preventing cardiotoxicity in a rodent model of doxorubicin (DOX)-induced cardiomyopathy. METHODS: Male Wistar rats (n = 7-11 per group) were divided into 4 subgroups, namely negative controls receiving intravenous saline (CON), positive controls receiving intravenous DOX (6 cycles; D-CON), and DOX-treated animals receiving either prophylactic (PRE, started 1 week before DOX) or conventionally applied (POST, started 1 month after DOX) combined heart failure therapy of oral bisoprolol, perindopril and eplerenone. Blood pressure, heart rate, body weight and echocardiographic parameters were monitored in vivo, whereas myocardial fibrosis, capillarisation, ultrastructure, myofilament function, apoptosis, oxidative stress and mitochondrial biogenesis were studied in vitro. RESULTS: The survival rate in the PRE group was significantly improved compared to D-CON (p = 0.0207). DOX increased the heart rate of the animals (p = 0.0193), while the blood pressure (p ≤ 0.0105) and heart rate (p = 0.0029) were significantly reduced in the PRE group compared to D-CON and POST. The ejection fraction remained preserved in the PRE group compared to D-CON or POST (p ≤ 0.0237), while none of the treatments could prevent the DOX-induced increase in the isovolumetric relaxation time. DOX decreased the rate of the actin-myosin cross-bridge cycle, irrespective of any treatment applied (p ≤ 0.0433). The myocardium of the D-CON and POST animals displayed pronounced ultrastructural damage, which was not apparent in the PRE group (p ≤ 0.033). While the DOX-induced apoptotic activity could be reduced in both the PRE and POST groups (p ≤ 0.0433), no treatment was able to prevent fibrotic remodelling or the disturbed mitochondrial biogenesis. CONCLUSION: For attenuating DOX-induced adverse myocardial effects, prophylactic cardioprotection has many advantages compared to a late-applied treatment.

[The efficacy and safety of edoxaban in non-valvular atrial fibrillation]. / Az edoxabán véralvadásgátló hatásossága és biztonságossága nonvalvuláris pitvarfibrillációban.

The significantly increased incidence of stroke and systemic embolisation caused by atrial fibrillation can be prevented by adequately adjusted anticoagulant therapy. Vitamin K antagonists effectively decrease the risk of thromboembolic events but this effect is influenced by many factors. The development of the new direct oral anticoagulant drugs (DOAC) in the last few years provided new opportunities for us to choose the suitable anticoagulant therapy. According to the results of the ENGAGE AF-TIMI 48 and ENSURE-AF multicenter, randomized trials, edoxaban, the recently introduced DOAC is equally effective as the traditional coumarin therapy, nevertheless, it ensures more tolerable anticoagulation for patients suffering from non-valvular atrial fibrillation. Orv Hetil. 2018; 159(12): 466-469.

Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial.

AIMS: This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. METHODS AND RESULTS: A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 ± 9 years, CHA2DS2-VASc score 1.4 ± 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT ≥ 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16-72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 ± 10.0) than in ERACE (28.8 ± 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. CONCLUSION: Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01767558.

[Risk of thromboembolism in atrial fibrillation]. / Thromboemboliás kockázat pitvarfibrillációban.

Atrial fibrillation is considered as one of the cardiovascular pandemics of our days due to its increasing prevalence and the significant burden on healthcare systems. Management, especially prevention of thromboembolism associated with the arrhythmia is still a challenge even with recently available treatment options. Herein, the author reviews the possibilities of risk stratification and stroke prevention, which are important to all medical professionals who potentially encounter patients with this arrhythmia. Orv. Hetil., 2016, 157(38), 1511-1515.

[The importance of "free" nucleic acids in the non-invasive diagnostics]. / A "szabad" nukleinsavak jelentosége a noninvazív diagnosztikában.

There is a great interest to determine the physiological role of "free" nucleic acids, and to use them in the clinical diagnostics. These could be DNA, mRNA, microRNA and long non-coding RNA molecules, they are in the body fluids, like serum, tear, saliva, etc. Their exact role in the normal and pathological physiological processes is still in the focus of the research, while their use in the diagnostics is becoming more and more important. The use of "free" DNA in the non-invasive prenatal diagnosis is the first clinical application of the new generation sequencers, these methods are able to reach 99.9% specificity and sensitivity for the detection of the most common trisomies. There are promising results in their use in the diagnosis and classification of heart and cardiovascular diseases. In oncology the possibility to use the "liquid biopsy" captured the attention of not only researchers and clinicians, but the whole community. There is not enough data until today for the clinical utility and applicability of these methods. Orv. Hetil., 2016, 157(48), 1900-1909.

Predictors of cerebral microembolization during phased radiofrequency ablation of atrial fibrillation: role of the ongoing rhythm and the site of energy delivery.

BACKGROUND: Pulmonary vein isolation with phased radiofrequency current and use of a pulmonary vein ablation catheter (PVAC) has recently been associated with a high incidence of clinically silent brain infarcts on diffusion-weighted magnetic resonance imaging, and a high microembolic signal (MES) count detected by transcranial Doppler. We investigated the potential effects of the ongoing rhythm and the target vein during energy delivery (ED) on MES generation during PVAC ablations. METHODS AND RESULTS: A total of 735 EDs during 48 PVAC ablations were analyzed. MES counts were recorded for each ED and time-stamped for correlation with the ongoing rhythm and the target vein for each ED. Significantly higher MES counts were observed during ablations of the left-sided as compared with the right-sided pulmonary veins (P = 0.0003). Similarly, higher MES counts were detected during EDs in atrial fibrillation as compared with sinus rhythm when the temperature was >56°C (P < 0.0001). The ongoing rhythm had no effect on the number of MESs at lower temperatures during ablation. CONCLUSIONS: Both the ongoing rhythm during ED and the site of ablation influence microembolus generation during PVAC ablation procedures.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

INTRODUCTION: Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. METHODS: CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. RESULTS: A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II. CONCLUSION: SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

Atrial Fibrillation Related Coronary Embolism: Diagnosis in the Focus.

Atrial fibrillation (AF) is the most common arrhythmia in myocardial infarction (MI). AF can be caused by ischemia, and MI can be caused by AF. Additionally, 4-5% of MI cases are related to coronary embolism (CE), and one-third of cases are attributed to AF. Our aim was to investigate the prevalence of AF-related CE cases among 3 consecutive years of STEMI cases. We also aimed to reveal the diagnostic accuracy of the Shibata criteria scoring system and the role of thrombus aspiration. Among 1181 STEMI patients, 157 had AF (13.2%). By using the Shibata's diagnostic criteria, 10 cases were classified as 'definitive' and 31 as 'probable' CE. After re-evaluation, a further five cases were classified as 'definitive'. Further analysis of the 15 CE cases revealed that CE was more prevalent in patients with previously known (n = 10) compared to those with new-onset (n = 5) AF (16.7% vs. 5.1%, p = 0.024). A PubMed search was performed, and 40 AF-related cases were found where the Shibata's criteria could be applied. Further, 31 cases could be classified as 'definitive', 4 as 'probable' and, in 5 cases, the embolic origin could be excluded. In 40% of reported cases and in 47% of our cases, thrombus aspiration helped in diagnosis.

Right superior pulmonary vein parameter determined by three-dimensional transesophageal echocardiography is an independent predictor of the outcome after cryoballoon isolation of the pulmonary veins.

BACKGROUND: A direct comparison of three-dimensional transesophageal echocardiography (3DTEE) and cardiac computed tomography imaging has demonstrated good inter-technique agreement for the following pulmonary vein (PV) parameters: the ostium area of the right superior PV (RSPV) and its major (a) and minor axis (b) diameters, the left lateral ridge and the minor axis (b) diameter of the left superior PV. Herein, under investigation, was the predictive value of these parameters for arrhythmia recurrence (AR) after PV isolation with the 28 mm second generation cryoballoon (CBG2). METHODS: One hundred eleven patients (67 men, mean age 58.06 ± 10.58 years) undergoing 3DTEE before PV isolation with the CBG2 for paroxysmal atrial fibrillation were followed. "Point by point" redo intervention was offered in case of AR and reconnected PVs were defined. RESULTS: During a mean follow-up of 617 ± 258.86 days, 65 (58.9%) patients remained free of AR. Longer RSPV b was found to be the only significant predictor for AR (hazard ratio [HR] 1.059; 95% confidence interval [CI] 1.000-1.121; p = 0.048). RSPV b ≥ 28 mm resulted in a threefold (HR 3.010; 95% CI 1.270-7.134, p = 0.012) increase in the risk of AR. The association of RSPV b with AR was independent of the biophysical parameters of cryoapplications. In 25 "redo" patients, reconnections were found 1.75 times more likely in the RSPV than in the other 3 PVs altogether. CONCLUSIONS: Right superior PV b measured with 3DTEE might be a significant predictor of AR after PV isolation with the CBG2. In case of RSPV b exceeding 28 mm, alternative PV isolation techniques or use of a larger balloon might be considered.

Omecamtiv mecarbil augments cardiomyocyte contractile activity both at resting and systolic Ca2+ levels.

AIMS: Heart failure with reduced ejection fraction (HFrEF) is a disease with high mortality and morbidity. Recent positive inotropic drug developments focused on cardiac myofilaments, that is, direct activators of the myosin molecule and Ca2+ sensitizers for patients with advanced HFrEF. Omecamtiv mecarbil (OM) is the first direct myosin activator with promising results in clinical studies. Here, we aimed to elucidate the cellular mechanisms of the positive inotropic effect of OM in a comparative in vitro investigation where Ca2+ -sensitizing positive inotropic agents with distinct mechanisms of action [EMD 53998 (EMD), which also docks on the myosin molecule, and levosimendan (Levo), which binds to troponin C] were included. METHODS: Enzymatically isolated canine cardiomyocytes with intact cell membranes were loaded with Fura-2AM, a Ca2+ -sensitive, ratiometric, fluorescent dye. Changes in sarcomere length (SL) and intracellular Ca2+ concentration were recorded in parallel at room temperature, whereas cardiomyocyte contractions were evoked by field stimulation at 0.1 Hz in the presence of different OM, EMD, or Levo concentrations. RESULTS: SL was reduced by about 23% or 9% in the presence of 1 µM OM or 1 µM EMD in the absence of electrical stimulation, whereas 1 µM Levo had no effect on resting SL. Fractional sarcomere shortening was increased by 1 µM EMD or 1 µM Levo to about 152%, but only to about 128% in the presence of 0.03 µM OM. At higher OM concentrations, no significant increase in fractional sarcomere shortening could be recorded. Contraction durations largely increased, whereas the kinetics of contractions and relaxations decreased with increasing OM concentrations. One-micromole EMD or 1 µM Levo had no effects on contraction durations. One-micromole Levo, but not 1 µM EMD, accelerated the kinetics of cardiomyocyte contractions and relaxations. Ca2+ transient amplitudes were unaffected by all treatments. CONCLUSIONS: Our data revealed major distinctions between the cellular effects of myofilament targeted agents (OM, EMD, or Levo) depending on their target proteins and binding sites, although they were compatible with the involvement of Ca2+ -sensitizing mechanisms for all three drugs. Significant part of the cardiotonic effect of OM relates to the prolongation of systolic contraction in combination with its Ca2+ -sensitizing effect.

Technically Challenging Percutaneous Interventions of Chronic Total Occlusions Are Associated with Enhanced Platelet Activation.

Percutaneous coronary intervention (PCI) is a frequently performed treatment option for recanalization in patients with chronic total occlusion (CTO). As CTO-PCIs are often complicated and challenging for interventionalists, the stressful and damaging nature of the procedure can be remarkable, thus platelets can be easily activated. Our aim was to investigate the effect of CTO-PCI on platelet activation and the expression of selected circulating microRNAs (miR) of platelet and endothelium origin after CTO-PCI. In this study, 50 subjects after CTO-PCI were enrolled. Blood samples were obtained before PCI, at 2 days and 3-6 months after the procedure to measure the degree of platelet activation and the level of plasma miR-223, miR-181b, and miR-126. Patients were divided based on the characteristics of the intervention. Patients with higher Japanese CTO scores and longer duration of PCI showed significantly elevated platelet P-selectin positivity (p = 0.004 and p = 0.013, respectively) 2 days after the procedure compared to pre-PCI and increased concentration of soluble P-selectin 3-6 months after the intervention (higher Japanese CTO score: p = 0.028 and longer duration of PCI: p = 0.023) compared to baseline values. Shorter total stent length caused a significantly lower miR-181b expression at 3-6 months after the intervention (p = 0.031), while no difference was observed in miR-223 and miR-126. One stent thrombosis occurred during the follow-up period. Although these technically challenging CTO-PCIs may cause enhanced platelet activation right after the intervention and long-term endothelial cell dysfunction, these interventions are not associated with more adverse clinical events.

Mortality on DOACs Versus on Vitamin K Antagonists in Atrial Fibrillation: Analysis of the Hungarian Health Insurance Fund Database.

PURPOSE: Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period. METHODS: The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled. FINDINGS: A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA2DS2-VASc score segment and in those with fewer (0-1) bleeding risk factors (HR = 0.50, CI 0.34-0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year. IMPLICATIONS: Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA2DS2-VASc score, and those with fewer bleeding risk factors.