Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial.

BACKGROUND: Both transcatheter edge-to-edge repair (TEER) of mitral regurgitation or left atrial appendage closure (LAAC) require periprocedural anticoagulation with unfractionated heparin (UFH) that is administered either before or immediately after transseptal puncture (TSP). The optimal timing of UFH administration (before or after TSP) is unknown. The Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions trial (STOP CLOT Trial) was designed to determine if early anticoagulation is effective in reducing ischemic complications without increasing the risk of periprocedural bleeding. METHODS: The STOP CLOT trial is a multicenter, prospective, double-blind, placebo-controlled, randomized trial. A total of 410 patients scheduled for TEER or LAAC will be randomized 1:1 either early UFH administration (iv. bolus of 100 units/kg UFH or placebo, given after obtaining femoral vein access and at least 5 minutes prior to the start of the TSP) or late UFH administration (iv. bolus of 100 units/kg UFH or placebo given immediately after TSP). Prespecified preliminary statistical analysis will be performed after complete follow-up of the first 196 randomized subjects. To ensure blinding, a study nurse responsible for randomization and UFH/placebo preparation is not involved in the care of the patients enrolled into the study. The primary study endpoint is a composite of (1) major adverse cardiac and cerebrovascular events (death, stroke, TIA, myocardial infarction, or peripheral embolization) within 30 days post-procedure, (2) intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transesophageal echocardiography, or (3) occurrence of new ischemic lesions (diameter ≥4 mm) on brain magnetic resonance imaging performed 2 to 5 days after the procedure. The safety endpoint is the occurrence of moderate or severe bleeding complications during the index hospitalization. CONCLUSIONS: Protocols of periprocedural anticoagulation administration during structural interventions have never been tested in a randomized clinical trial. The Stop Clot trial may help reach consensus on the optimal timing of initiation of periprocedural anticoagulation. CLINICAL TRIALS REGISTRATION NUMBER: The study protocol is registered at ClinicalTrials.gov, identifier NCT05305612.

The Comparative Effectiveness and Safety of Different Anticoagulation Strategies for Treatment of Left Atrial Appendage Thrombus in the Setting of Chronic Anticoagulation for Atrial Fibrillation or Flutter.

PURPOSE: To compare effectiveness of different treatments for atrial fibrillation (AF) patients who were scheduled for cardioversion (CV) or ablation (CA) presenting with left atrium appendage (LAA) thrombus despite chronic oral anticoagulation therapy (OAC). METHODS: This was a retrospective cohort study. We analyzed 2014-2019 medical records of patients scheduled for CV or CA of AF who were diagnosed with LAA thrombus despite optimal OAC and had a follow-up transesophageal echocardiogram (TOE). Changes in treatment were divided into the following groups: switch to a drug with different mechanism of action, switch to a drug with similar mechanism of action, initiation of combination therapy, or deliberate no change in treatment. Patients with contraindications to non-vitamin K antagonists were excluded from the analysis. RESULTS: We analyzed data of 129 patients comprising 181 cycles of treatment. The overall effectiveness of LAA thrombus dissolution was 51.9% regardless of the number of cycles and 42.6% for the first cycle of treatment. Any change of treatment was more effective than deliberate no change-OR 2.97 [95% CI: 1.07-8.25], P = 0.031, but no particular strategy seemed to be more effective than the other. Left atrium area (OR 0.908 [95% CI: 0.842-0.979]) and number of treatment cycles (OR 0.457 [95% CI: 0.239-0.872]) were both adversely related to thrombus resolution. There was one ischemic and three bleeding adverse events during the treatment. CONCLUSION: LAA thrombus resolution in patients already on OAC may require a change of previous OAC treatment but the overall effectiveness of dissolution seems to be about 50%.

A novel ECG-based algorithm to determine right ventricular lead placement in permanent pacemaker patients (RVpace study).

INTRODUCTION: Fluoroscopy guidance alone is not sufficient for the accurate localization of the pacing lead (PL) in the right ventricle (RV) during implantation of the cardiac implantable electronic device (CIED). The aim of this study was to create a surface electrocardiogram (ECG) algorithm based on paced QRS (pQRS) morphology to accurately localize PL position in the RV. METHODS AND RESULTS: Thirty consecutive patients scheduled for catheter ablation of right heart arrhythmias were enrolled. After the elimination of index arrhythmia pacing from the RV interventricular septum (IVS), apex and free wall was performed and pQRS were recorded. The pacing site was verified both by fluoroscopy and transthoracic echocardiography. After a careful analysis of pQRS, a stepwise algorithm was developed to aid the proper positioning of the PL in RV. The algorithm was later prospectively validated in 31 pacemaker patients undergoing an elective generator exchange. A clear R wave in I, II, and V5 leads indicated proximal IVS. For a reliable indication of other RV sites, four ECG leads were crucial I, II, V5, and V6. A prospective evaluation of the algorithm revealed 90.3% agreement between RV lead localization obtained by ECG and echocardiography, with sensitivity of 92.5% (95% confidence interval [CI], 83.2%-100.0%) and a positive predictive value of 96.0% (95% CI, 89.0%-100.0%) for desired lead locations in RV. CONCLUSION: A simple ECG algorithm can reliably differentiate between the sites of permanent PL implantation in the RV in CIED recipients.

New diagnostic pathways urgently needed. Protocol of PET Guidance I pilot study: positron emission tomography in suspected cardiac implantable electronic device-related infection.

BACKGROUND: Cardiovascular implantable electronic device (CIED) infection is a complication of increasing incidence. We present a protocol of an observational case control clinical trial "Positron Emission Tomography Combined With Computed Tomography (PET CT) in Suspected Cardiac Implantable Electronic Device Infection, a Pilot Study - PET Guidance I" (NCT02196753). AIM: The aim of this observational clinical trial is to assess and standardise diagnostic algorithms for CIED infections (lead-dependent infective endocarditis, generator pocket infection, fever of unknown origin) with PET CT in Poland. METHODS AND RESULTS: Study group will consist of 20 patients with initial diagnosis of CIED-related infection paired with a control group of 20 patients with implanted CIEDs, who underwent PET CT due to other non-infectious indications and have no data for infectious process in follow-up. All patients included in the study will undergo standard diagnostic pro-cess. Conventional/standard diagnostic and therapeutic process will consist of: medical interview, physical examination, laboratory tests, blood cultures; imaging studies: echocardiography: transthoracic (TTE), and, if there are no contraindications transoesophageal, computed tomography scan for pulmonary embolism if indicated; if there are abnormalities in other systems, decisions concerning further diagnostics will be made at the physician's discretion. As well as standard diagnostic procedures, patients will undergo whole body PET CT scan to localise infection or inflammation. Diagnosis and therapeutic decision will be obtained from the Study Committee. Follow-up will be held within six months with control visits at three and six months. During each follow-up visit, all patients will undergo laboratory tests, two blood cultures collected 1 h apart, and TTE. In case of actual clinical suspicion of infective endocarditis or local generator pocket infection, patients will be referred for further diagnostics. Endpoints for the results assessment - primary endpoints are to standardise PET CT in the diagnostic process: sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis made by PET CT; secondary endpoints are: assessment of usefulness of PET CT for detection of remote infective complications (metastatic abscesses, infected pulmonary emboli), incidence of particular localisations of infection, influence of PET CT on therapeutic decision: confirmation or change of decision based on PET CT, safety and complications of diagnostic process of CIED-related infections with PET CT. CONCLUSIONS: Evaluation of PET CT use for device-related infections in a case control study may be conclusive and improve diagnostic pathway.

Osteoprotegerin in patients with degenerative aortic stenosis and preserved left-ventricular ejection fraction.

OBJECTIVES: The aim of the present study was to evaluate value of osteoprotegerin (OPG) in patients with degenerative aortic stenosis and preserved left-ventricular ejection fraction. METHODS: We have prospectively followed 70 patients with aortic stenosis (mean aortic gradient ≥15 mmHg) and preserved left-ventricular ejection fraction for 1 year. In all patients, echocardiography and blood tests (OPG, lipids, high-sensitivity C-reactive protein) were performed at baseline and after 1 year of follow-up. Detailed medical history including atherosclerotic risk factors was obtained. The control group consisted of 20 healthy individuals with normal echocardiographic findings. Rapid progression of aortic stenosis was defined as more than 7 mmHg increase in mean aortic gradient per year. RESULTS: Osteoprotegerin concentrations were significantly higher in patients with aortic stenosis (P < 0.0001) and correlated with the degree of aortic stenosis. In multivariable regression model analysis, age (ß = 0.015, P < 0.0001), mean aortic gradient (ß = 0.04, P = 0.0078) and presence of coronary artery disease (ß = 0.111, P = 0.0408) were the only independent determinants of plasma OPG concentrations. There was no association between OPG concentrations and coronary artery disease risk factors: male sex, smoking, hypertension and hypercholesterolemia. Concentrations of high-sensitivity C-reactive protein correlated positively with OPG levels only in nonsurgical patients (with lower degree of stenosis) (r = 0.34, P = 0.01). Aortic stenosis progression was related to body mass, diabetes, triglyceride concentrations, metabolic syndrome and left-ventricular systolic volume. In multivariate analysis, only metabolic syndrome was an independent predictor of aortic stenosis progression. CONCLUSION: Osteoprotegerin concentrations are linked to the presence and severity of aortic stenosis. Metabolic syndrome was the only independent predictor of degenerative aortic stenosis progression.

Utility of automated template matching for the interpretation of pace mapping in patients ablated due to outflow tract ventricular arrhythmias.

AIMS: One of the disadvantages of classic pace mapping (PM) is the operator's subjective interpretation. The aim of this single-centre retrospective study was to evaluate the value of automated template matching (AMT) in patients ablated due to ventricular outflow tract arrhythmias (OTAs). METHODS AND RESULTS: From an overall group of 105 patients with OTA who were scheduled for transcatheter ablation (TA), AMT was accessible in 42 patients [21 right ventricular outflow tract (RVOT), 21 left ventricular outflow tract (LVOT), 28 women, aged 51.5 ± 12.7 years]. We used AMT to compare spontaneous arrhythmia ORS (spontQRS) with paced QRS complexes during PM in sites where radiofrequency (RF) applications were successful and in sites where RF applications were unsuccessful. The concordance was presented in per cents as objective matching scores (OMS). Then, at the successful ablation sites, we examined the relationship between OMS and the visual interpretation of PM was presented as electrophysiologists matching scores (EMS). The OMS of PM at sites of successful ablation varied from 78 to 99% (mean 94.1 ± 3.8) and from 47 to 95% (mean 80.2 ± 12.6%) at sites of unsuccessful ablation. Pace mapping in unsuccessful RF sites was significantly less similar to spontQRS morphologies than in successful RF sites (P = 0.0001). There was a significant correlation between OMS and EMS (r = 0.82; P < 0.0001). The OMS that indicated optimal ablation site was 89% (sensitivity = 95%; specificity = 80%). The mean OMS for successful sites at RVOT (95.1 ± 1.8%) and LVOT (93.1 ± 4.9%) were not different (P = 0.0551). CONCLUSION: This analysis revealed that AMT is a valuable technique for the interpretation of PM and for the identification of successful ablation sites in OTA.

Novel algorithm for arrhythmogenic focus localization in patients with right ventricular outflow tract arrhythmias.

BACKGROUND: Previously presented new electrocardiography (ECG) algorithm for localization of arrhythmogenic focus (AFo) in right ventricular outflow tract (RVOT) was based on spontaneous arrhythmia QRS morphology analysis. The aim of this study was to estimate the clinical value of our RVOT algorithm in a prospective study. METHODS AND RESULTS: Algorithm validation was made on 62 patients with RVOT arrhythmias (45 women), mean age 41.6 ± 14.3 years, scheduled for transcatheter ablation. Results of preablation ECG analysis with RVOT algorithm were matched with successful ablation sites and statistical indices: sensitivity (sens), specificity (spec), and positive and negative predictive values (PPV, NPV) were calculated for algorithm and for each of 9 RVOT zones (septal and free wall). An algorithm precisely localized AFo in 57 out of 62 patients (sens 91.3%, spec 99%, PPV 91%, NPV 98.8%). Sensitivity values for superior RVOT aspect (71% patients) varied from 88% to 100%, specificity from 95.9% to 100%; PPV values from 85.7% to 100%, NPV from 92.5% to 100%. Although the total number of patients was relatively small in the 2 remaining RVOT aspects (29% patients) high values (sens, spec, PPV, NPV) were gained for intermediate and inferior zones. CONCLUSIONS: On the basis of spontaneous arrhythmia QRS analysis, a novel algorithm was built for preablation localization of RVOT arrhythmia in 1 of the 9 RVOT zones. Prospective analysis of our ECG algorithm confirmed that it is a valuable tool to predict the site of successful ablation in patients with RVOT arrhythmias.

High concentrations of B-type natriuretic peptide and left ventricular diastolic dysfunction in patients with paroxysmal/persistent atrial fibrillation as possible markers of conversion into permanent form of arrhythmia: 1-year prospective evaluation.

BACKGROUND: Atrial fibrillation (AF) may cause electrical and structural atrial remodelling, leading to progression from paroxysmal to permanent form of arrhythmia. Predictors of such a transition have not yet been well established. AIM: To assess the role of B-type natriuretic peptide (BNP) and left ventricular (LV) diastolic impairment in prediction of progression from paroxysmal/persistent AF to permanent AF. METHODS: The study group consisted of 154 patients (84 males, mean age 65.8 +/- 10 years) with paroxysmal (51%) or persistent (49%) AF and normal LV systolic function. All patients had BNP level and echocardiographic parameters of diastolic LV dysfunction measured at baseline and after one-year follow up. RESULTS: After one-year follow-up, 15 (9.5%) patients developed permanent AF. These patients had significantly higher baseline and one-year BNP values than the remaining patients (96.0 v. 41 pg/mL, p < 0.005, and 151.1 v. 32.5 pg/mL, p < 0.0001, respectively). Also echocardiographic indices of LV diastolic dysfunction were abnormal in patients who developed permanent AF. Stepwise logistic regression analysis revealed that baseline BNP level had independent prognostic value in predicting permanent AF development (OR 1.06, CI 1.01-1.12, p < 0.0162). The area under ROC curve was 0.787. CONCLUSIONS: Patient with normal systolic LV function and paroxysmal or persistent AF are likely to progress into permanent AF when they have increased BNP levels and echocardiographic signs of LV diastolic dysfunction.

Subacute cardiac perforations associated with active fixation leads.

AIMS: Having several recently published reports on increased rate of cardiac perforation with some lead models as background, we assess the relation between cardiac perforations and models of leads used. METHODS AND RESULTS: All pacing and defibrillation leads implantations between 1 January 2007 and 31 March 2008 were analysed retrospectively. There were 2247 leads implanted in 1419 patients aged 67.6 +/- 14.1, 1200 (53%) active and 1047 (47%) passive fixation leads. Cardiac perforation occurred in eight patients (0.5%). The number of perforations does not differ significantly between the pacemaker and implantable cardioverter defibrillator implantations (five and three cases, respectively, P = 0.13). All perforations were associated with the active fixation leads implantation (8 vs. 0, P < 0.01). Only four models of leads were associated with perforations, but the risk of their use was not statistically significantly increased, when compared with other active fixation leads placed in the adequate position. CONCLUSIONS: The incidence of cardiac perforation related to pacing and defibrillation leads is low. The use of active fixation leads is associated with an increased risk of cardiac perforation. We did not find any correlation between the perforation rate and any particular model of the implanted lead.

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure.

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.

[Acute inferolateral myocardial infarction as the first manifestation of left atrial myxoma -- a case report]. / Sluzak lewego przedsionka powiklany zawalem serca sciany dolno-bocznej.

A case of a young patient admitted to our hospital due to acute myocardial infarction is presented. Coronary angiography revealed normal coronary arteries. Echocardiography performed immediately after coronary angiography showed the presence of the left atrial myxoma. Three days later the patient underwent urgent surgery with a favourable outcome. The role of echocardiography in detecting atrial myxoma and mechanisms of myocardial infarction caused by this anomaly are discussed.

Gene therapy of coronary artery disease with phvegf165--early outcome.

BACKGROUND: Gene therapy is a new, experimental method of treatment in patients with coronary artery disease (CAD). AIM: To determine the safety and efficacy of gene encoding vascular endothelial growth factor (VEGF165) administered directly into the myocardium as the single treatment or combined with coronary artery by-pass grafting (CABG). METHODS: VEGF gene transfer was performed in 22 patients (20 male, 2 female, ages from 48 to 73 years old). A 200 micro g of the plasmid encoding VEGF165 was injected into the ischaemic myocardium which could not be surgically revascularised in patients undergoing CABG (n=14), and 400 micro g - in patients without CABG (n=8). The value of ejection fraction (EF), myocardial perfusion, angiogram, ventriculography, and nitroglycerine consumption as well as quality of life were evaluated pre- and postoperatively. RESULTS: The majority of patients had no complications and no fatal outcome was observed. Two patients developed acute myocardial infarction. Left ventricular function values improved and the majority of patients were free from angina 6 months after surgery. Patients reported improved quality of life and a reduction in nitroglycerine usage. A reduction in the ischaemic defects detected by SPECT was also observed. In some patients angiography revealed improved collateral filling. CONCLUSIONS: Direct myocardial administration of genes encoding VEGF165 can be an effective method of treatment in patients with chronic and advanced CAD either as a supplementary treatment or as a single therapy.