Myocardial Damage, Inflammation, Coagulation, and Platelet Activity During Catheter Ablation Using Radiofrequency and Pulsed-Field Energy.

BACKGROUND: Pulsed-field ablation (PFA) represents a new, nonthermal ablation energy for the ablation of atrial fibrillation (AF). Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation activation. OBJECTIVES: This study aimed to compare the systemic response in patients undergoing pulmonary vein isolation (PVI) using pulsed-field and radiofrequency (RF) energy. METHODS: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or pulsed-field (Farapulse, Boston-Scientific) energy. Markers of myocardial damage (troponin I), inflammation (interleukin-6), coagulation (D-dimers, fibrin monomers, von Willebrand antigen and factor activity), and platelet activation (P-selectin, activated GpIIb/IIIa antigen) were measured before the procedure (T1), after trans-septal puncture (T2), after completing the ablation in the left atrium (T3), and 1 day after the procedure (T4). RESULTS: A total of 65 patients were enrolled in the pulsed-field ablation (n = 33) and RF ablation (n = 32) groups. Both groups were similar in baseline characteristics (age 60.5 ± 12.7 years vs 64.0 ± 10.7 years; paroxysmal AF: 60.6% vs 62.5% patients). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09 ± 11:57 min vs 151:19 ± 41:25 min; P < 0.001; 36:00 ± 8:05 min vs 115:58 ± 36:49 min; P < 0.001). Peak troponin release was substantially higher in the PFA group (10,102 ng/L [IQR: 8,272-14,207 ng/L] vs 1,006 ng/L [IQR: 603-1,433ng/L]). Both procedures were associated with similar extents (>50%) of platelet and coagulation activation. The proinflammatory response 24 h after the procedure was slightly but nonsignificantly higher in the RF group. CONCLUSIONS: Despite 10 times more myocardial damage, pulsed-field ablation was associated with a similar degree of platelet/coagulation activation, and slightly lower inflammatory response. (The Effect of Pulsed-Field and Radiofrequency Ablation on Platelet, Coagulation and Inflammation; NCT05603637).

Clinical characteristics and mortality in all Czech patients after pacemaker implantation in the last decade.

Background and aims: Analysis of mortality from the national health registries and data from a specific central registry dealing with the implantation of pacemakers (REPACE) in Czech patients. Methods and results: Retrospective observational analysis of pacemakers' implantation in all Czech patients [n = 82,791; 47,070 (56.9%) men, 75.9 ± 10.4 years old] between 2010 and 2021. Almost 114,000 pacemakers were implanted between 2010 and 2021, of which 27.9% were single-chamber, 67.4% were dual-chamber and 4.6% were biventricular. The annual number of implantations has been steadily increasing with a 6% annual decline in 2020 with increased mortality and reductions in care provided, likely related to COVID-19. The observed 5-year relative survival was 88.6% (overall survival 60.6%) and the 10-year relative survival was 75.9% (overall survival 32.7%). Causes of death 5ary according to the age of the patient. The highest difference 1n the reported numbers in the REPACE Registry did not exceed 2% in comparison with the National Register of Reimbursed Health Services. Conclusion: This study followed all Czech patients with pacemaker's implantation in between 2010 and 2021. The annual number of 1mplantations has been steadily 1ncreasing. Patients with implanted pacemakers had a significantly higher mortality than the average population. Number of patients in the registry corresponded almost perfectly with the National Register of Reimbursed Health Services.

Challenges in prospective observational studies evaluating pressure ulcer costs: how to price the items correctly.

OBJECTIVE: Pressure ulcers (PUs) are a significant healthcare problem with a negative impact on patients' quality of life and incurring substantial healthcare expenses. Our study aimed to analyse the costs of treating PUs in hospitalised patients in the Czech Republic, in the context of current treatment procedures and price levels, and to pilot-test the detailed methodology developed. METHOD: A prospective, observational, non-interventional study was conducted at the Clinic of Anesthesiology, Resuscitation and Intensive Medicine, the Internal Medicine Department and the Surgical Department of the University Hospital Ostrava. The study included all hospitalised patients with a PU from March-May 2021. Data were collected using the hospital information system. A bottom-up, person-based approach to cost analysis was used, based on a comprehensive cost structure using accurate patient-specific consumption records. RESULTS: The length of hospitalisations ranged from 1-31 (mean: 12.7) days. The average cost of PU treatment per hospitalisation was calculated at €1579. The average daily cost of PU treatment was €179, including antibiotic therapy (ATB) and €112 without ATB. Most of the costs were associated with ATB (38.6%) and caregivers' time (35.9%). Based on the results, a predictive model was developed to estimate the cost of treating a hospitalised patient with a PU, which could be used in future research to assess the costs of treating these patients. CONCLUSION: We have faced many challenges in the methodology of preparation of cost analysis (e.g., how to count amorphous topical agents and sprays, how to properly identify PUs, how to price the positioning aids and mattresses, and how to relate the ATB treatment to the PU). This analysis provides important input for developing a comprehensive and more accurate methodology for monitoring PU costs in hospitalised patients, applicable in clinical practice for inpatient healthcare providers.

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

INTRODUCTION: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). METHODS: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). RESULTS: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. CONCLUSION: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Mortality related to pressure ulcers in Czech Republic - Analyses of national health registries.

BACKGROUND: Pressure ulcers/pressure injuries (PUs/PIs) relate to decreasing quality of life, prolonged hospitalisation, the increased economic cost of care, and increased mortality. That's why this study focused on one of the mentioned factors - mortality. OBJECTIVES: The study analyses national data in the Czech Republic to map the mortality phenomenon comprehensively based on data from national health registries. METHOD: The retrospective, nationwide cross-sectional data analysis of data collected by the National Health Information System (NHIS) has been provided in the period 2010-2019 with a special focus on 2019. Hospitalisations with PUs/PIs were identified by reporting L89.0-L89.9 diagnosis as a primary or secondary hospitalisation diagnosis. We also included all the patients who died in the given year with an L89 diagnosis reported in 365 days prior the death. RESULTS: In 2019, 52.1% of patients with reported PUs/PIs were hospitalised, and 40.8% were treated on an outpatient basis. The most common underlying cause of death mortality diagnosis (43.7%) in these patients was the diseases of the circulatory system. Patients who die in a healthcare facility while hospitalised with an L89 diagnosis generally have a higher category of PUs/PIs than persons who die outside a healthcare facility. CONCLUSION: The proportion of patients dying in a health facility is directly proportional to the increasing PUs/PIs category. In 2019, 57% of patients with PUs/PIs died in a healthcare facility, and 19% died in the community. In 24% of patients who died in the healthcare facility, PUs/PIs were reported 365 days before the death.

Role of adjuvant therapy in intermediate-risk cervical cancer patients - Subanalyses of the SCCAN study.

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

Stratification of lymph node metastases as macrometastases, micrometastases, or isolated tumor cells has no clinical implication in patients with cervical cancer: Subgroup analysis of the SCCAN project.

BACKGROUND: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis. METHODS: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges. RESULTS: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group. CONCLUSIONS: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication.

Effectiveness of ICD therapy in real clinical practice. The Olomouc ICD Registry.

BACKGROUND: Clinical parameters linked to a low benefit of ICD implantation and increased mortality risks are needed for an individualized assessment of potential benefits and risks of ICD implantation. METHODS: Analysis of a prospective registry of all patients hospitalized from 2009 to 2019 in a single centre for a first implantation of any type of ICD. RESULTS: A total of 2,681 patients were included in the registry. Until the end of follow-up (38.4 ± 29.1 months), 682 (25.4%) patients died. The one-year mortality in all patients, the one-year CV mortality, the three-year mortality in all patients, and the three-year CV mortality were 7.8%, 5.7%, 20.6%, and 14.8%, respectively. There was a statistically significant difference when the subgroups were compared according to the type of cardiomyopathy. No significant difference was found between primary and secondary prevention and between the types of devices. Male gender, age ≥ 75 years, diabetes mellitus, and atrial fibrillation were associated with a significantly increased mortality risk. CONCLUSION: In an analysis of a long-term follow-up of 2,681 ICD patients, we found no mortality difference between patients with ischemic or non-ischemic cardiomyopathy and in the device type. A higher mortality risk was found in men, patients older than 75 years, diabetics, and those with atrial fibrillation.

Pharmacotherapy of diabetes mellitus in patients with heart failure - a nation-wide analysis of contemporary treatment.

AIM: Retrospective national sub-analysis of antidiabetic pharmacotherapy in patients with diabetes mellitus (DM) and heart failure (HF) based on data reported to the National Register of Paid Health Services in the Czech Republic between 2012-2018. METHODOLOGY AND RESULTS: In 2012, there were 75,022 patients with HF and DM (i.e. 42.5% of patients with HF), 6 years later 117,265 (i.e. 41.0% of HF patients in 2018). The most represented antidiabetic drug was metformin (45.6%). Of the insulins and analogues, glargine showed the largest positive trend (5.8% 2012; 14.8% 2018). Empagliflozin was the most prescribed SGLT-2 inhibitor (1.8% in 2018). A decrease in prescribing was observed for saxagliptin (0.5% 2012; 0.1% 2018) and for sulfonylurea derivates - gliclazide (13.0% 2012; 10.3% in 2018) and glimepiride (12.9% 2012; 9.0% 2018). Linagliptin was the most prescribed dipeptidyl peptidase inhibitor (0.7% 2012; 6.8% 2018). CONCLUSION: In the Czech Republic, between 2012 and 2008, there was an increase in prevalence of patients with heart failure and concomitant diabetes mellitus, their proportion being similar. In correspondence with other registries, metformin was used mostly. A positive trend was observed in prescription of DDP-4 and SGLT-2 inhibitors, while there was a significant decrease in patients taking sulfonylureas.

COVID-19 vaccine booster significantly decreases the risk of intensive care unit hospitalization in heart failure patients during the Omicron variant wave: A population-based study.

Background: Heart failure (HF) patients are at higher risk of severe coronavirus disease 2019 (COVID-19). The Omicron variant has many novel mutations including those in the spike protein, leading to questions about vaccine effectiveness. The aim of this analysis was to evaluate the effectiveness of the COVID-19 vaccine with or without a booster (i.e., after the third dose) during the Omicron variant wave. Methods: Chronic heart failure patients in the Czech Republic were included in the analysis. COVID-19 infection was monitored from January 1st 2022 to March 31st 2022. The analysis was conducted on data collected in the National Health Information System. Vaccine effectiveness of vaccinated (with or without booster) vs. unvaccinated patients was analyzed for incidence of COVID-19, COVID-19-related hospitalizations, COVID-19 related intensive care unit admissions, and COVID-19 related mechanical ventilation/extracorporeal membrane oxygenation treatment. Findings: From a total 165,453 HF patients in the Czech Republic, 9,728 contracted COVID-19 (22.9% of them not vaccinated, 23.2% vaccinated and 53.8% vaccinated and boosted). Risk of intensive care unit (ICU) hospitalization was 7.6% in the unvaccinated group, 4.8% in the vaccinated group and 2.9% in the boosted group. The calculated effectiveness of the COVID-19 vaccine in prevention of ICU hospitalization in the vaccinated group was 41.9 and 76.6% in the boosted group. Interpretation: The results demonstrated moderate vaccine effectiveness in the prevention of severe COVID-19 in vaccinated but not boosted HF patients. Much stronger effectiveness was found in those who were vaccinated and boosted.

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

How the COVID-19 pandemic influences the prevalence of pressure injuries in the Czech Republic: A nationwide analysis of a health registry in 2020.

BACKGROUND: COVID-19 significantly influences the overall patient status and, in severe symptomatology, the ability to move and the low oxygenation of the tissue for the ventilated patient in Intensive Care Units (ICU). There is a higher risk for Pressure injuries (PIs) development. OBJECTIVES: The nationwide analyses of the National health register aimed to compare the prevalence of PIs reported before the pandemic COVID-19 started and during the pandemic in 2020. METHOD: A retrospective, nationwide cross-sectional analysis of data regarding the STROBE checklist collected by the National Health Information System (NHIS), focusing on the PIs reporting based on the International Classification of Diseases (ICD-10) diagnoses L89.0-L89.9 for PIs in 2020. The data from the pandemic period of COVID-19 in 2020 were compared to the prevalence of PI cases in the period 2010-2019 in the Czech Republic in all hospitalized patients. RESULTS: The total number of admissions for L89 in 2020 was 14,441, of which 1509 (10.4%) also had COVID-19. In the ICU were 4386 admissions, 12.1% of which also had COVID-19. A higher proportion of PIs is observed in patients hospitalized with COVID-19 than in patients without COVID-19 (2.62% vs 0.81%, respectively 1.05% vs 0.46% when standardized to the 2013 ESP = European Standard Population). In patients hospitalized in ICU, 3.68% with COVID-19 had PIs vs 1.42% without COVID-19 had PIs (1.97% vs 0.81% using the 2013 ESP). CONCLUSION: The national health registers analyses have proven that the prevalence of PIs was higher among patients hospitalized with the SARS-CoV-2 infection.

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study.

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2'-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker's ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin.

A ten-year follow-up of the prevalence of pressure injuries in the Czech Republic: Analysis of the National Registry.

The study aims to follow up on the analysis of Pressure injuries (PIs) prevalence conducted between 2007 and 2014 and after the new methodological requirements for PIs surveillance establishment at the national level. A retrospective, nationwide cross-sectional analysis of data regarding the STROBE checklist was collected by the National Health Information System (NHIS). The International Classification of Diseases (ICD-10) diagnoses L89.0-L89.9 for PIs were used in the period 2010-2019. A total of 264 442 records of patients with diagnoses of L89.0-L89.9 were identified from 2010 to 2019 (26 444 patients per year on average). The numbers are increasing every year, and there is a 40% increase between 2010 and 2019. When comparing recorded PIs, the percentage of PIs occurrence in category I decreased, and the number of PIs in category IV increased in the second analysed period. Still, in absolute numbers, there is an increase across all categories. The age of patients with recorded PIs also rose slightly in the second analysed period. We have proven the PIs prevalence increase in an ageing population.

Hypertension outcomes of adrenalectomy for unilateral primary aldosteronism.

PURPOSE: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA). METHODS: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. RESULTS: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4. CONCLUSION: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs.

4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation.

BACKGROUND: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk. OBJECTIVES: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17. METHODS: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA2DS2-VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat. RESULTS: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA2DS2-VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses. CONCLUSIONS: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944).

Post-recurrence survival in patients with cervical cancer.

BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.

The annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer.

PURPOSE: Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. METHODS: Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. RESULTS: Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. CONCLUSION: The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally.

Trends in the treatment and survival of heart failure patients: a nationwide population-based study in the Czech Republic.

AIMS: A retrospective nationwide observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018. METHODS AND RESULTS: Prevalence of heart failure (HF) patients increased from 176 496 (1679.4 per 100 000 population) in 2012 to 285 745 (2689.0 per 100 000 population) patients in 2018 (mean age 74.4 ± 12.8 years). In the last years, a stable incidence of HF patients was observed (544 per 100 000 population in 2016 vs. 551 per 100 000 population in 2018; P = 0.310). Mortality rate decreased from 20.55% in 2012 to 15.89% in 2018. The number of hospitalized patients remained similar (318.2 per 100 000 population in 2012 vs. 311.8 per 100 000 population in 2018; P = 0.479). The most used drugs were diuretics (173 295; 60.6%) and beta-blockers (178 823; 62.6%), followed by angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (angiotensin-converting enzyme inhibitors 120.581; 42.2%; angiotensin II receptor blockers 47 216; 16.5%). Even though the whole number of implanted devices in HF patients increased steadily (from 25 205 in 2012 to 45 363 in 2018), the prevalence of all devices (pacemakers and defibrillators) in the HF patients remained about the same (14.3% in 2012; 15.9% in 2018). CONCLUSIONS: The study included all patients with HF in the Czech Republic. These are the first nationwide data of HF epidemiology in the Eastern bloc. The incidence of HF remains stable in the last years. Due to aging of the population, the prevalence of HF significantly increased in the last 6 years. Despite a continuous increase in the prevalence of HF and a suboptimal utilization of its pharmacological therapy, mortality decreased, and the number of hospitalized patients remained the same.