'Evaluation of beta-2-microglobulin and neuron-specific enolase as prognostic factors in patients over 65 years of age with frailty syndrome hospitalized for acute coronary syndrome'.

BACKGROUND: The aim of the study is to assess the value of beta-2-microglobulin (B2M) and neuron-specific enolase (NSE) as prognostic factors in the population of patients over 65 years of age with frailty hospitalized due to acute coronary syndrome (ACS). METHODS: Patients aged ≥65 years with ACS were included. Assessment of frailty was carried out using the FRAIL scale. The measurement of NSE and B2M was carried out three times during hospitalization: (1) at the time of admission, (2) on the second day of hospitalization, (3) on the seventh day of hospitalization, or the day of discharge if it was before the seventh day. The primary endpoint was all-cause mortality, and the secondary endpoint was unscheduled rehospitalization. RESULTS: Of the 127 patients, frailty was identified in 39.3%. Multivariate analysis of variance showed significantly higher levels of NSE (P = 0.012) and B2M (P < 0.001) in patients with frailty compared to the nonfrail group and significant changes in marker levels during hospitalization - decreased NSE (P < 0.001) and increased B2M levels (P < 0.001). Elevated B2M-1 level was an independent marker of the occurrence of frailty [odds ratio (OR), 1.98 (1.09-4.00); P = 0.044], and the optimal cutoff point for the diagnosis of frailty was 2.85 mg/l [area under the curve (AUC), 0.718 (0.632-0.795)] with sensitivity 52% and specificity 84.4% (P < 0.001). Elevated NSE-3 level was associated with all-cause mortality, and each 1 ng/ml increase in NSE-3 increased the risk of death by 1.07-fold [OR, 1.07 (1.03-1.10]). Meanwhile, elevated B2M-3 level was associated with unscheduled rehospitalization, and each 1 mg/l increase in B2M-3 increased the risk of unscheduled rehospitalization by 1.21-fold [OR, 1.21 (1.03-1.42)]. The Harrell's C-index for all-cause mortality was higher for NSE-3 [0.820 (95% confidence interval {CI}, 0.706-0.934)] compared to frailty assessed by the FRAIL scale [0.715 (95% CI, 0.580-0.850)], which means that additional NSE-3 assessment may improve the prediction of all-cause mortality. However, Uno's C-Statistic analysis showed that the difference was not statistically significant (Pr>chi-square 0.556). Harrell's C-index for unscheduled rehospitalization was higher for frailty assessed by the FRAIL scale compared to B2M-3. CONCLUSION: Monitoring NSE and B2M marker levels in patients over 65 years of age with frailty and ACS does not provide additional benefits in terms of prognostic ability compared to tests assessing frailty. B2M, assessed upon hospital admission and monitoring NSE and B2M levels during hospitalization may be considered in the diagnosis of frailty and risk stratification in a group of patients for whom currently available frailty diagnostic tools cannot be used.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Nicotine and Cardiovascular Health: When Poison is Addictive - a WHF Policy Brief.

Nicotine is universally recognized as the primary addictive substance fuelling the continued use of tobacco products, which are responsible for over 8 million deaths annually. In recent years, the popularity of newer recreational nicotine products has surged drastically in many countries, raising health and safety concerns. For decades, the tobacco industry has promoted the myth that nicotine is as harmless as caffeine. Nonetheless, evidence shows that nicotine is far from innocuous, even on its own. In fact, numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems. Tobacco and recreational nicotine products are commercialized in various types and forms, delivering varying levels of nicotine along with other toxic compounds. These products deliver nicotine in profiles that can initiate and perpetuate addiction, especially in young populations. Notably, some electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) can deliver concentrations of nicotine that are comparable to those of traditional cigarettes. Despite being regularly advertised as such, ENDS and HTP have demonstrated limited effectiveness as tobacco cessation aids in real-world settings. Furthermore, ENDS have also been associated with an increased risk of cardiovascular disease. In contrast, nicotine replacement therapies (NRT) are proven to be safe and effective medications for tobacco cessation. NRTs are designed to release nicotine in a slow and controlled manner, thereby minimizing the potential for abuse. Moreover, the long-term safety of NRTs has been extensively studied and documented. The vast majority of tobacco and nicotine products available in the market currently contain nicotine derived from tobacco leaves. However, advancements in the chemical synthesis of nicotine have introduced an economically viable alternative source. The tobacco industry has been exploiting synthetic nicotine to circumvent existing tobacco control laws and regulations. The emergence of newer tobacco and recreational nicotine products, along with synthetic nicotine, pose a tangible threat to established tobacco control policies. Nicotine regulations need to be responsive to address these evolving challenges. As such, governments should regulate all tobacco and non-medical nicotine products through a global, comprehensive, and consistent approach in order to safeguard tobacco control progress in past decades.

Current Spectrum and Outcomes of Infarct-Related Cardiogenic Shock: Insights from the CULPRIT-SHOCK Registry and RCT.

BACKGROUND: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry. METHODS: In total, 1,075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialised centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1-year. RESULTS: Mean age was 68 years and 260 (25 %) were women. 13.5 %, 30.9 %, and 55.6 % had 1-vessel, 2-vessel, and 3-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0 %. 54.2 % of the patients had cardiac arrest before admission. TIMI 3 patency of the infarct vessel after PCI was achieved in 83.6 % of all patients. Mechanical circulatory support was applied in one third of patients. Total mortality after 30 days and one year was 47.6 % and 52.9 %. Mortality after one year was highest in patients with LM coronary artery stenosis (63.5 %), followed by 3-vessel- (56.6 %), 2-vessel- (49.8 %), and 1-vessel-CAD (38.6 %), respectively. Mechanical complications were rare (21/1008; 2.1 %) but associated with a high mortality of 66.7 % after 1 year. CONCLUSIONS: In specialised centres in Europe short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depending on the extent of coronary artery disease. Therefore, there is still need for improvement of care to improve prognosis of infarct-related CS.

Clinical Outcomes in Older Patients with Atrial Fibrillation: Insights from the GARFIELD-AF Registry.

BACKGROUND: Oral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment patterns, and impact of anticoagulation upon clinical outcomes with respect to age. METHODS: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme. RESULTS: Of 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years. CONCLUSIONS: Older patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs.

Management of myocardial infarction complicated by cardiogenic shock: Expert opinion of the Association of Intensive Cardiac Care and Association of Cardiovascular Interventions of the Polish Society of Cardiology.

Despite significant advances in interventional cardiology and mechanical circulatory support (MCS) techniques, outcomes for patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) remain suboptimal. This expert consensus aims to provide information on the current management of patients with MI complicated by CS in Poland and to propose solutions, including systemic ones, for all stages of care. The document uses data from the Polish PL-ACS Registry of Acute Coronary Syndromes, which includes records of more than 820 000 hospital admissions. We describe the role of medical rescue teams, highlighting the necessity to expand their range of competencies at the level of prehospital care. We emphasize the importance of treating the underlying cause of CS and direct patient transfer to centers capable of performing percutaneous coronary interventions. We present current recommendations of scientific societies on MCS use. We underline the role of the Cardiac Shock Team in the management of patients with MI complicated by CS. Such teams should comprise an interventional cardiologist, a cardiothoracic surgeon, and an intensive care physician. Patients should be transferred to highly specialized CS centers, following the example of so-called Cardiac Shock Care Centers described in some other countries. We propose criteria for the operation of such centers Other important aspects discussed in the document include the role of rehabilitation, multidisciplinary care, and long-term follow-up of treatment outcomes. The document was developed in cooperation with experts from different scientific societies in Poland, which illustrates the importance of interdisciplinary care in this patient population.

Position of the Polish Cardiac Society on therapeutic targets for LDL cholesterol concentrations in secondary prevention of myocardial infarctions.

Cardiovascular diseases account for 43% of deaths in Poland. The COVID-19 pandemic increased the number of cardiovascular deaths by as much as 16.7%. Lipid metabolism disorders are observed in about 20 million Poles. Lipid disorders are usually asymptomatic, they cause a significant increase in the risk of cardiovascular diseases. Up to 20% of patients who experience an acute coronary syndrome (ACS) may experience a recurrence of a cardiovascular event within a year, and up to 40% of these patients may be re-hospitalized. Within 5 years after a myocardial infarction, 18% of patients suffer a second ACS and 13% have got a stroke. Lipid-lowering therapy is an extremely important element of comprehensive management, both in primary and secondary prevention, and its main goal is to prevent or extend the time to the onset of heart or vascular disease and reduce the risk of cardiovascular events. A patient with a history of ACS belongs to the group of a very high risk of a cardiovascular event due to atherosclerosis. In this group of patients, low-density lipoprotein cholesterol levels should be aimed below 55 mg/dl (1.4 mmol/l). Many scientific guidelines define the extreme risk group, which includes not only patients with two cardiovascular events within two years, but also patients with a history of ACS and additional clinical factors: peripheral vascular disease, multivessel disease (multilevel atherosclerosis), or multivessel coronary disease, or familial hypercholesterolemia, or diabetes with at least one additional risk factor: elevated Lp(a) >50 mg/dl or hsCRP >3 mg/l, or chronic kidney disease (eGFR <60 ml/min/1.73 m²). In this group of patients, the LDL-C level should be aimed at below 40 mg/dl (1.0 mmol/l). Achieving therapeutic goals in patients after ACS should occur as soon as possible. For this purpose, a high-dose potent statin should be added to the therapy at the time of diagnosis, and ezetimibe should be added if the goal is not achieved after 4-6 weeks. Combination therapy may be considered in selected patients from the beginning. After 4-6 weeks of combination therapy, if the goal is still not achieved, adding a proprotein convertase subtilisin/kexin type 9 protein inhibitor or inclisiran should be considered. In order to increase compliance with the recommendations, Polish Cardiac Society and Polish Lipid Society propose to attach in the patient's discharge letter a statement clearly specifying what drugs should be used and what LDL-C values should be achieved. It is necessary to cooperate between the patient and the doctor, to follow the recommendations and take medicines regularly, to achieve and maintain therapeutic goals.

The impact of frailty on in-hospital complications in elderly patients with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is linked to a range of in-hospital complications, and age is recognized as risk factor for adverse events. Discrepancies between physiological and chronological age are explained by frailty. However, the relationship between frailty and in-hospital complications is not clear. METHODS: Assessment of frailty in patients was carried out using the FRAIL scale. In-hospital complications assessed included, bleeding, infection, arrhythmia, acute kidney injury (AKI), delirium, stroke/transient ischemic attack (TIA), liver injury, hypoglycemia, length of stay in the cardiac care unit (CCU). RESULTS: Of the 174 patients, frailty was identified in 39.1% and pre-frailty in 29.9%. Frailty was associated with a higher incidence of all types of bleeding (frail vs. robust: 45.5% vs. 16.7%, P < 0.001) and infection (54.4% vs. 11.1%, P < 0.001), including pneumonia/lower respiratory tract infections (LRTI) and urinary tract infections (UTI). Incidence of antibiotic therapy (52.9% vs. 13.0%, P < 0.001), atrial fibrillation (AF) (47.1% vs. 9.3%, P < 0.001), AKI (57.3% vs. 20.4%, P < 0.001), delirium (52.9% vs. 3.7%, P < 0.001), liver injury, were higher in frail patients (17.6% vs. 0, P = 0.001), whilst their length of stay in the CCU was longer (4 days (2-6.5) vs. 2 days (2-3), P < 0.001). Infections, pneumonia/LRTI, antibiotic therapy during hospitalization, the incidence of AF and liver injury were more often in patients with pre-frailty compared to the robust group. After adjustment for potential confounders, frailty remained independently associated with an increased risk of infection (OR: 3.3 [1.6-7.0]), including pneumonia/LRTI (OR: 2.5 [1.1-5.8]) and UTI (OR: 4.8 [1.8-12.5]). Frail individuals had an increased requirement for antibiotic therapy (OR: 3.9 [1.9-8.1]), and greater risk of AF (OR: 3.5 [1.3-9.3]), AKI (OR: 2.6 [1.2-5.3]) delirium (OR: 11.7 [4.8-28.7]), as well as having to stay longer in the CCU (> 3 days) (OR: 3.7 [1.9-7.3]). CONCLUSIONS: Frailty was associated with an increased risk of numerous in-hospital complications in elderly patients who had been hospitalized with ACS.

ARTERIAL HYPEROXIA AND MORTALITY IN PATIENTS UNDERGOING VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION.

ABSTRACT: Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can easily lead to supranormal oxygenation. The impact of hyperoxygenation beyond the early VA-ECMO support phase is unexplored. We sought to investigate its association with short- and long-term mortality. Methods: A total of 10,615 arterial blood gases of 179 patients undergoing VA-ECMO between 2013 and 2018 in our cardiosurgical tertiary center were analyzed for partial pressure of oxygen (PaO2) and its association with in-hospital, 90-day, and 1-year mortality. Patients were stratified into terciles (T) based on PaO2. Results: The median systemic PaO2 during VA-ECMO was 122 mm Hg (Q1-Q3, 111-158 mm Hg) and was significantly higher in 90-day nonsurvivors versus survivors (134 mm Hg [Q1-Q3, 114-175 mm Hg] vs. 114 mm Hg [Q1-Q3, 109-136 mm Hg]; P < 0.001). The incidence of mortality increased at all time points tested after VA-ECMO implantation along with the increasing terciles of PaO2. The lowest mortality rates were noted for patients with median PaO2 values of <115 mm Hg (T1), whereas patients with median PaO2 values of >144 mm Hg (T3) had the highest mortality rates. Bonferroni multiple testing analysis found the T3 of PaO2 to be a predictor of decreased 90-day survival in comparison with T1 (P < 0.001) and T2 (P = 0.002). Multivariable Cox regression analyses for in-hospital, 90-day, and 1-year mortality showed a significant association of the T3 compared with the T2 and the T1 of PaO2 to mortality across all endpoints. Conclusion: Hyperoxygenation during VA-ECMO might be associated with increased all-cause mortality. The results of our study further document the known toxicity of hyperoxygenation in general critical care patients and mark the need to focus specifically on VA-ECMO patients.

Troponin T and Survival following Cardiac Surgery in Patients Supported with Extracorporeal Membrane Oxygenation for Post-Cardiotomy Shock.

BACKGROUND: While troponin is an established biomarker of cardiac injury, its prognostic significance in post-cardiotomy cardiogenic shock patients supported by venoarterial extracorporeal membrane oxygenation (PCCS-VA-ECMO) remains unclear. OBJECTIVE: This study aimed to assess the correlation between early post-operative troponin T levels and both short-term and long-term mortality outcomes in this cohort. METHODS: We evaluated 1457 troponin T measurements from 102 PCCS-VA-ECMO patients treated from 2013 to 2018 at a specialized cardio-surgical and transplantation center. Emphasis was placed on troponin concentrations at 24-48 h post-surgery, post-VA-ECMO implantation, and peak troponin levels in relation to VA-ECMO weaning, as well as 90-day and one-year mortality. RESULTS: No significant association was observed between troponin T levels post-VA-ECMO implantation and 90-day mortality (median: 1338 ng/L for overall, 1529 ng/L for survivors vs. 1294 ng/L for non-survivors; p = 0.146) or between peak troponin levels and 90-day mortality (median: 3583 ng/L for overall, 3337 ng/L for survivors vs. 3666 ng/L for non-survivors; p = 0.709). Comprehensive multivariate models showed no correlation between troponin levels and various mortality endpoints. Notably, age, procedure urgency, type, LVEF pre-surgery, Euroscore II, prior cardiac arrest, and VA-ECMO duration were not linked with troponin release. Hemodiafiltration emerged as the strongest mortality risk factor [HR 2.4]. CONCLUSIONS: Isolated early Troponin T release and peak troponin T were not associated, while organ complications were linked with VA-ECMO weaning or short- and long-term prognosis. The results underscore the multi-organ implications of PCCS in determining survival.

Comparison of the prognostic value of frailty assessment tools in patients aged ≥ 65 years hospitalized in a cardiac care unit with acute coronary syndrome.

BACKGROUND: Frailty is associated with adverse events in elderly patients with acute coronary syndrome (ACS). Our aim was to compare the prognostic value of four frailty scales in patients aged ≥ 65 years hospitalized with ACS in a cardiac care unit (CCU). METHODS: Patients aged ≥ 65 years with ACS were included. Frailty was assessed using the Fried frailty scale (reference standard), the Edmonton Frail Scale (EFS), the FRAIL scale, and the Clinical frailty scale (CFS). The primary end point was all-cause mortality and the secondary end point was unscheduled rehospitalization. RESULTS: One hundred and seventy four patients aged ≥ 65 years with ACS were recruited. The median follow-up was 637.5 days. Frailty was identified in 41.4%, 40.2%, 39.1% and 36.3% patients by the Fried frailty scale, EFS, FRAIL scale and CFS, respectively. The agreement coefficients were 0.88, 0.86, and 0.79 for the FRAIL scale, EFS and CFS, respectively. In the Cox regression model, frailty was associated with all-cause mortality regardless of the scale used (univariate: hazard ratio [HR] 95% CI = 10.5, 2.4-46.8 Fried frailty scale; 12.0, 2.7-53.4 FRAIL scale; 7.1, 2.0-25.2 EFS; 8.3, 2.4-29.6 CFS. Multivariate: HR = 5.1, 1.1-23.8 Fried frailty scale; 5.7, 1.2-26.8 FRAIL scale; 3.7, 1.0-14.0 EFS; 4.2, 1.1-15.9 CFS). The FRAIL scale had the highest HR. In the univariate analysis, frailty was associated with unscheduled rehospitalization (HR = 3.2, 1.7-6.0 Fried frailty scale; 3.4, 1.8-6.3 FRAIL scale; 3.5, 1.8-6.6 EFS; 3.1, 1.7-5.8 CFS). In the multivariate analysis, only the EFS independently predicted unscheduled rehospitalization (HR = 2.2, 1.1-4.63). CONCLUSIONS: Frailty assessed by the Fried frailty scale, FRAIL scale, EFS and CFS is associated with all-cause mortality and unscheduled rehospitalization in elderly patients hospitalized in a CCU with ACS. The adjusted HR of the FRAIL scale for all-cause mortality was the highest among the scales compared, whereas the EFS was an independent predictor of unscheduled rehospitalization. These data should be taken into consideration when choosing a frailty assessment tool.

Do baseline characteristics and treatments account for geographical disparities in the outcomes of patients with newly diagnosed atrial fibrillation? The prospective GARFIELD-AF registry.

OBJECTIVE: In patients with newly diagnosed atrial fibrillation (AF), do baseline risk factors and stroke prevention strategies account for the geographically diverse outcomes. DESIGN: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation is a prospective multinational non-interventional registry of patients with newly diagnosed AF (n=52 018 patients). SETTING: Investigator sites (n=1317) were representative of the care settings/locations in each of the 35 participating countries. Treatment decisions were all determined by the local responsible clinicians. PARTICIPANTS: The patients (18 years and over) with newly diagnosed AF had at least 1 investigator-determined stroke risk factor and patients were not required to meet specific thresholds of risk score for anticoagulant treatment. MAIN OUTCOMES AND MEASURES: Observed 1-year event rates and risk-standardised rates were derived. RESULTS: Rates of death, non-haemorrhagic stroke/systemic embolism and major bleeding varied more than three-to-four fold across countries even after adjustment for baseline factors and antithrombotic treatments. Rates of anticoagulation and antithrombotic treatment varied widely. Patients from countries with the highest rates of cardiovascular mortality and stroke were among the least likely to receive oral anticoagulants. Beyond anticoagulant treatment, variations in the treatment of comorbidities and lifestyle factors may have contributed to the variations in outcomes. Countries with the lowest healthcare Access and Quality indices (India, Ukraine, Argentina, Brazil) had the highest risk-standardised mortality. CONCLUSION: The variability in outcomes across countries for patients with newly diagnosed AF is not accounted for by baseline characteristics and antithrombotic treatments. Residual mortality rates were correlated with Healthcare Access and Quality indices. The findings suggest the management of patients with AF needs to not only address guideline indicated and sustained anticoagulation, but also the treatment of comorbidities and lifestyle factors. TRIAL REGISTRATION NUMBER: NCT01090362.

Repetitive use of LEvosimendan in Ambulatory Heart Failure patients (LEIA-HF) - The rationale and study design.

PURPOSE: Clinical practice forces the necessity to conduct a clinical trial concerning the group of outpatients with chronically advanced heart failure in III or IV NYHA functional class, frequently requiring hospitalizations due to HF exacerbation, and often left without any additional therapeutic option. The current trial aims to determine the efficacy and safety of repeated levosimendan infusions in the group of severe outpatients with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: LEIA-HF (LEvosimendan In Ambulatory Heart Failure Patients) is a multicentre, randomized, double-blind, placebo-controlled, phase 4 clinical trial to determine whether the repetitive use of levosimendan reduces the incidence of adverse cardiovascular events in ambulatory patients with chronic, advanced HFrEF. A total of 350 patients will be randomized in a 1:1 ratio to receive either levosimendan or placebo, which will be administered as continuous 24 â€‹h infusions, every 4 weeks for 48 weeks (12 infusions in total - phase I), and followed by double-blind 6 visits, every 4 weeks (phase II of the trial including the option of restarting levosimendan or placebo, based on the fulfillment of additional criteria). The primary endpoint for efficacy assessment will be death from any cause or unplanned hospitalization for HF assessed together, whichever occurs first, in a 12-month follow-up period. CONCLUSIONS: A well-designed study with a consistent protocol, including the drug side effects, comprehensive clinical assessment, appropriate definition of endpoints, and monitoring therapy, may provide a complete overview of the effectiveness and safety profile of the repetitive levosimendan administration in ambulatory severe HFrEF patients.

Association between dose of catecholamines and markers of organ injury early after out-of-hospital cardiac arrest.

BACKGROUND: Catecholamines are recommended as first-line drugs to treat hemodynamic instability after out-of-hospital cardiac arrest (OHCA). The benefit-to-risk ratio of catecholamines is dose dependent, however, their effect on metabolism and organ function early after OHCA has not been investigated. METHODS: The Post-Cardiac Arrest Syndrome (PCAS) pilot study was a prospective, observational, multicenter study. The primary outcomes of this analysis were association between norepinephrine/cumulative catecholamines doses and neuron specific enolase (NSE)/lactate concentration over the first 72 hours after resuscitation. The association was adjusted for proven OHCA mortality predictors and verified with propensity score matching (PSM). RESULTS: Overall 148 consecutive OHCA patients; aged 18-91 (62.9 ± 15.27), 41 (27.7%) being female, were included. Increasing norepinephrine and cumulative catecholamines doses were significantly associated with higher NSE concentration on admission (r = 0.477, p < 0.001; r = 0.418, p < 0.001) and at 24 hours after OHCA (r = 0.339, p < 0.01; r = 0.441, p < 0.001) as well as with higher lactate concentration on admission (r = 0.404, p < 0.001; r = 0.280, p < 0.01), at 24 hours (r = 0.476, p < 0.00; r = 0.487, p < 0.001) and 48 hours (r = 0.433, p < 0.01; r = 0.318, p = 0.01) after OHCA. The associations remained significant up to 48 hours in non-survivors after PSM. CONCLUSIONS: Increasing the dose of catecholamines is associated with higher lactate and NSE concentration, which may suggest their importance for tissue oxygen delivery, anaerobic metabolism, and organ function early after OHCA.

One-Year Outcome of Glycoprotein IIb/IIIa Inhibitor Therapy in Patients with Myocardial Infarction-Related Cardiogenic Shock.

BACKGROUND: We aimed to evaluate the effect of intravenous glycoprotein IIb/IIIa receptor inhibitors (GPIs) on in-hospital survival and mortality during and at the 1-year follow-up in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) complicated by cardiogenic shock (CS), who were included in the Polish Registry of Acute Coronary Syndromes (PL-ACS). METHODS: From 2003 to 2019, 466,566 MI patients were included in the PL-ACS registry. A total of 10,193 patients with CS received PCI on admission. Among them, GPIs were used in 3934 patients. RESULTS: The patients treated with GPIs were younger, had lower systolic blood pressure on admission, required inotropes and intra-aortic balloon pump (IABP) support more frequently, and showed a lower efficacy of coronary angioplasty. In both groups, the same rates of in-hospital adverse events were observed. A lower mortality rate was reported in the group treated with GPIs 12 months after admission (54.9% vs. 57.9%, p = 0.002). Therapy with GPI was an independent factor reducing the risk of mortality in the 12-month follow-up. CONCLUSIONS: The addition of GPIs to the standard pharmacotherapy combined with PCI in patients with MI and CS on admission reduced the risk of death in the 12-month follow-up period without increasing in-hospital adverse event rates.

Current applications and outcomes of venoarterial extracorporeal membrane oxygenation based on 6 years of experience: risk factors for in­hospital mortality.

INTRODUCTION: Data regarding venoarterial extracorporeal membrane oxygenation (VA ECMO) as a temporary circulatory support in cardiogenic shock (CS) for Central Europe are scarce. OBJECTIVES: The aim of the study was to disclose indications, in-hospital, and long-term (1-year) mortality along with risk factors. PATIENTS AND METHODS: The study is a retrospective investigation of patients who underwent VA ECMO for CS at a cardiosurgical tertiary center, from January 2013 to June 2018. A broad spectrum of pre- and postimplantation factors was tested using univariable analysis. RESULTS: A total of 198 patients met the inclusion criteria. The median (interquartile range) duration of support was 207 (91­339) hours, with no significant disparity among hospital survivors and nonsurvivors (P = 0.09). A total of 40.4% of patients died during ECMO support, while the joined in-hospital and 6-month mortality progressed to 65.2%, and 1-year mortality to 67.2%; 9% underwent a subsequent heart transplantation. Main adverse events were bleeding (76%), infection (56%), neurologic injury (15%), and limb ischemia (15%). Multiorgan failure was the most decisive risk factor of in-hospital mortality (odds ratio, 4.45; P <⁠0.001). Patients with postcardiotomy CS had a significantly lower out-of-hospital survival rate than the nonsurgical group (32.3% vs 45%; log-rank P = 0.037). CONCLUSION: The study showed survival benefit, despite frequent complications. The protocol focusing on proper candidate selection and timing can positively impact patient survival. Additional risk reduction can be achieved with a further increase of the team experience with ECMO.

Impact of Center Volume on Outcomes in Myocardial Infarction Complicated by Cardiogenic Shock: A CULPRIT-SHOCK Substudy.

Background Little is known about the impact of center volume on outcomes in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to investigate the association between center volume, treatment strategies, and subsequent outcome in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results In this subanalysis of the randomized CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, study sites were categorized based on the annual volume of acute myocardial infarction complicated by cardiogenic shock into low-/intermediate-/high-volume centers (<50; 50-100; and >100 cases/y). Subjects from the study/compulsory registry with available volume data were included. Baseline/procedural characteristics, overall treatment, and 1-year all-cause mortality were compared across categories. n=1032 patients were included in this study (537 treated at low-volume, 240 at intermediate-volume, and 255 at high-volume centers). Baseline risk profile of patients across the volume categories was similar, although high-volume centers included a larger number of older patients. Low-/intermediate-volume centers had more resuscitated patients (57.5%/58.8% versus 42.2%; P<0.01), and more patients on mechanical ventilation in comparison to high-volume centers. There were no differences in reperfusion success despite considerable differences in adjunctive pharmacological/device therapies. There was no difference in 1-year all-cause mortality across volume categories (51.1% versus 56.5% versus 54.4%; P=0.34). Conclusions In this study of patients with acute myocardial infarction complicated by cardiogenic shock, considerable differences in adjunctive medical and mechanical support therapies were observed. However, we could not detect an impact of center volume on reperfusion success or mortality.

World Heart Federation Roadmap on Atrial Fibrillation - A 2020 Update.

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world's population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great.

Development and Validation of a Practical Model to Identify Patients at Risk of Bleeding After TAVR.

OBJECTIVES: No standardized algorithm exists to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR). The aim of this study was to generate and validate a useful predictive model. BACKGROUND: Bleeding events after TAVR influence prognosis and quality of life and may be preventable. METHODS: Using machine learning and multivariate regression, more than 100 clinical variables from 5,185 consecutive patients undergoing TAVR in the prospective multicenter RISPEVA (Registro Italiano GISE sull'Impianto di Valvola Aortica Percutanea; NCT02713932) registry were analyzed in relation to Valve Academic Research Consortium-2 bleeding episodes at 1 month. The model's performance was externally validated in 5,043 TAVR patients from the prospective multicenter POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) database. RESULTS: Derivation analyses generated a 6-item score (PREDICT-TAVR) comprising blood hemoglobin and serum iron concentrations, oral anticoagulation and dual antiplatelet therapy, common femoral artery diameter, and creatinine clearance. The 30-day area under the receiver-operating characteristic curve (AUC) was 0.80 (95% confidence interval [CI]: 0.75-0.83). Internal validation by optimism bootstrap-corrected AUC was 0.79 (95% CI: 0.75-0.83). Score quartiles were in graded relation to 30-day events (0.8%, 1.1%, 2.5%, and 8.5%; overall p <0.001). External validation produced a 30-day AUC of 0.78 (95% CI: 0.72-0.82). A simple nomogram and a web-based calculator were developed to predict individual patient probabilities. Landmark cumulative event analysis showed greatest bleeding risk differences for top versus lower score quartiles in the first 30 days, when most events occurred. Predictivity was maintained when omitting serum iron values. CONCLUSIONS: PREDICT-TAVR is a practical, validated, 6-item tool to identify patients at risk of bleeding post-TAVR that can assist in decision making and event prevention.