Effects of Serelaxin in Patients with Acute Heart Failure.

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).

One-Year Outcomes after PCI Strategies in Cardiogenic Shock.

BACKGROUND: Among patients with acute myocardial infarction, cardiogenic shock, and multivessel coronary artery disease, the risk of a composite of death from any cause or severe renal failure leading to renal-replacement therapy at 30 days was found to be lower with percutaneous coronary intervention (PCI) of the culprit lesion only than with immediate multivessel PCI. We evaluated clinical outcomes at 1 year. METHODS: We randomly assigned 706 patients to either culprit-lesion-only PCI or immediate multivessel PCI. The results for the primary end point of death or renal-replacement therapy at 30 days have been reported previously. Prespecified secondary end points at 1 year included death from any cause, recurrent myocardial infarction, repeat revascularization, rehospitalization for congestive heart failure, the composite of death or recurrent infarction, and the composite of death, recurrent infarction, or rehospitalization for heart failure. RESULTS: As reported previously, at 30 days, the primary end point had occurred in 45.9% of the patients in the culprit-lesion-only PCI group and in 55.4% in the multivessel PCI group (P=0.01). At 1 year, death had occurred in 172 of 344 patients (50.0%) in the culprit-lesion-only PCI group and in 194 of 341 patients (56.9%) in the multivessel PCI group (relative risk, 0.88; 95% confidence interval [CI], 0.76 to 1.01). The rate of recurrent infarction was 1.7% with culprit-lesion-only PCI and 2.1% with multivessel PCI (relative risk, 0.85; 95% CI, 0.29 to 2.50), and the rate of a composite of death or recurrent infarction was 50.9% and 58.4%, respectively (relative risk, 0.87; 95% CI, 0.76 to 1.00). Repeat revascularization occurred more frequently with culprit-lesion-only PCI than with multivessel PCI (in 32.3% of the patients vs. 9.4%; relative risk, 3.44; 95% CI, 2.39 to 4.95), as did rehospitalization for heart failure (5.2% vs. 1.2%; relative risk, 4.46; 95% CI, 1.53 to 13.04). CONCLUSIONS: Among patients with acute myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days was lower with culprit-lesion-only PCI than with immediate multivessel PCI, and mortality did not differ significantly between the two groups at 1 year of follow-up. (Funded by the European Union Seventh Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock.

BACKGROUND: In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial. METHODS: In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke. RESULTS: At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups. CONCLUSIONS: Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

The association between patterns of atrial fibrillation, anticoagulation, and cardiovascular events.

AIMS: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. METHODS AND RESULTS: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. CONCLUSION: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Predictors of NOAC versus VKA use for stroke prevention in patients with newly diagnosed atrial fibrillation: Results from GARFIELD-AF.

INTRODUCTION: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. METHODS: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ±â€¯antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. RESULTS: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. CONCLUSION: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.

Sudden Cardiac Death in Patients With Ischemic Heart Failure Undergoing Coronary Artery Bypass Grafting: Results From the STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: The risk of sudden cardiac death (SCD) in patients with heart failure after coronary artery bypass graft surgery (CABG) has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing, and clinical predictors of SCD after CABG. METHODS: Patients enrolled in the STICH trial (Surgical Treatment of Ischemic Heart Failure) who underwent CABG with or without surgical ventricular reconstruction were included. We excluded patients with prior implantable cardioverter-defibrillator and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. RESULTS: Over a median follow-up of 46 months, 113 of 1411 patients who received CABG without (n = 934) or with (n = 477) surgical ventricular reconstruction had SCD; 311 died of other causes. The mean left ventricular ejection fraction at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than did those who died of causes other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31- to 90-day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy, and left ventricular function, end-systolic volume index and B-type natriuretic peptide were most strongly associated with SCD. CONCLUSIONS: The monthly risk of SCD shortly after CABG among patients with a low left ventricular ejection fraction is highest between the first and third months, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative end-systolic volume index or B-type natriuretic peptide. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT0002359.

Multivessel versus culprit lesion only percutaneous revascularization plus potential staged revascularization in patients with acute myocardial infarction complicated by cardiogenic shock: Design and rationale of CULPRIT-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock (CS), up to 80% of patients present with multivessel coronary artery disease. Currently, the best revascularization strategy is unknown. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The CULPRIT-SHOCK study is a 706-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare culprit lesion only percutaneous coronary intervention (PCI) with possible staged non-culprit lesion revascularization versus immediate multivessel PCI in patients with CS complicating acute myocardial infarction. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of CULPRIT-SHOCK is 30-day mortality and severe renal failure requiring renal replacement therapy. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, an intermediate- and long-term follow-up at 6 and 12 months will be performed. Safety endpoints include the assessment of bleeding and stroke. CONCLUSIONS: The CULPRIT-SHOCK trial will address the question of optimal revascularization strategy in patients with multivessel disease and acute myocardial infarction complicated by CS.

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials.

OBJECTIVES AND BACKGROUND: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. METHODS: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. RESULTS: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the ß2-adrenergic receptor gene (ß2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. CONCLUSION: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

[Moderate or severe aquired valvular heart disease in pregnancy--what does determine the management? Experence, intuition or guidelines?]. / Umiarkowana lub ciezka nabyta wada sercaco--co decyduje o postepowaniu, doswiadczenie? intuicja? wytyczne?

Epidemiology of acquired valvular heart diseases has changed significantly over last decades. Degenerative aortic valve stenosis is the most common acquired valvular disease with high prevalence in elderly population. Another common disorder is ischemic mitral regurgitation secondary to myocardial infarction. Both above-mentioned heart disorders are not typical for women in reproductive age. Rheumatic heart valve disease has become infrequent in Polish population. Mitral stenosis, the most prevalent of rheumatic valvular disorders, affects 5% of pregnant women with heart disease and rheumatic aortic stenosis is responsible for 0.5-3% of heart diseases in this population. Despite the fact that acquired valvular disorders are becoming less common among pregnant women, they still remain an important issue and their management should be well known. Discussion about pregnancy should be a part of management of young women with valvular heart disease. Severe valve disorders should be corrected when planning pregnancy. The final management should always be based on collaborative decision made by the patient and health professionals.

Vascular complications after transcatheter aortic valve implantation (TAVI): risk and long-term results.

UNLABELLED: Vascular complications are the main safety limitations of transcatheter aortic valve implantation (TAVI). The aim of the study was to assess the incidents, predictors, and the impact of early vascular complications on prognosis after TAVI. This was a single-center analysis of vascular complications related to TAVI. Early vascular complications were defined as incidents within 30 days after TAVI and comprised complications related to transvascular: transfemoral/transsubclavian ,and transapical bioprosthesis implantation. Evaluated risk factors were: (1) clinical characteristics, (2) TAVI route, and (3) center experience. In patients with transvascular TAVI the impact of: (1) diameters of access arteries, vascular sheathes and difference between them, (2) arterial wall calcification, and (3) ProStar devices used for access site closure were assessed. Arterial wall calcification and arteries diameters were measured by 64-slice computer tomography. Arterial wall calcification was graded according to 5° scale. RESULTS: between 2009-2011; follow-up 1-23 months (12 ± 15.55), 83 consecutive patients, and 62-91 (81.10 ± 7.20) years, underwent TAVI: 67 (80.72%) patients had transvascular, and 16 (19.27%) patients had transapical bioprosthesis implantation. We noted 44 (53.01%) early vascular complications: 17 (20.48%) were major and 27 (32.53%) were minor incidents. Independent predictors of early vascular complications were: history of anaemia (OR 3.497: 95% CI [1.276-9.581]; p = 0.014), diabetes (OR 0.323: 95% CI [0.108-0.962]; p = 0.042), percutaneous coronary intervention performed as preparation for TAVI (OR 4.809: 95 % CI [1.172-19.736]; p = 0.029), and arterial wall calcification (OR 1.945: 95% CI [1.063-3.558]; p = 0.03). Of 6 (7.22%) in-hospital and 10 (12.98%) late deaths: 5 (83.33%) patients and 8 (80%) patients respectively had post-procedural vascular complications. Vascular complications, which occurred in 30-days after TAVI, predict late mortality (p = 0.036). Conclusions derived were: (1) TAVI patients with history of anaemia and diabetes required careful monitoring for early vascular complications. (2) If coronary intervention before TAVI is required, it should be performed in the time allowing vascular injuries to heal. (3) Calcification of access arteries is an independent predictor of post-procedural vascular complications; therefore, its estimation should be a regular element of preceding computer tomography. (4) Vascular complications seem to be predictors of late mortality after TAVI.

'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.

Incidence and prevalence of registered hypertension in Poland.

INTRODUCTION: Hypertension is a major factor related to morbidity and mortality in middle- and high­income countries. OBJECTIVES: The aim of the study was to assess the incidence and prevalence of registered hypertension in Poland in the years 2018-2022. PATIENTS AND METHODS: We used the public payer claims database to assess incidence and prevalence of registered hypertension. Definition of hypertension was based on the International Classification of Diseases, 10th Revision codes from I10 to I15. RESULTS: The number of registered hypertension cases during the analyzed period varied from 10.9 to 11 million. The prevalence was 0.5%, 0.5%, 0.5%, 0.4%, and 0.4% (P <0.001) in children (age <18 years) and 34.4%, 34.8%, 34.9%, 35.2%, and 35.2% (P <0.001) among adults in 2018, 2019, 2020, 2021, and 2022, respectively. In 2022, the mean (SD) age of persons with registered hypertension was 66.2 (14.1) years in women and 60.8 (14.8) years in men (P <0.001). The highest incidence of registered hypertension was found in men aged 55-59 years and in women aged 50-54 years. In the population aged up to 54 years, the registered prevalence of hypertension was higher among men, while in older age groups it was higher in women, reaching 94% and 87% in the oldest groups of women and men, respectively. CONCLUSIONS: In 2022, the number of patients with registered hypertension in Poland was close to 11 million, while the prevalence was 35.2% in adults and 0.4% in children. In the population under the age of 55 years, hypertension is more common in men, while women predominate in the older age groups.

Current spectrum and outcomes of infarct-related cardiogenic shock: insights from the CULPRIT-SHOCK registry and randomized controlled trial.

AIMS: 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 AND RESULTS: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-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. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-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. CONCLUSION: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS.

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.

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.

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.

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome.

UNLABELLED: Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions. MATERIALS AND METHODS: In 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed>50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries. RESULTS: In all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p<0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p<0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p<0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p<0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p<0.05). CONCLUSIONS: In acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

ESC Working Group on Valvular Heart Disease Position Paper: assessing the risk of interventions in patients with valvular heart disease.

AIMS: Risk scores provide an important contribution to clinical decision-making, but their validity has been questioned in patients with valvular heart disease (VHD), since current scores have been mainly derived and validated in adults undergoing coronary bypass surgery. The Working Group on Valvular Heart Disease of the European Society of Cardiology reviewed the performance of currently available scores when applied to VHD, in order to guide clinical practice and future development of new scores. METHODS AND RESULTS: The most widely used risk scores (EuroSCORE, STS, and Ambler score) were reviewed, analysing variables included and their predictive ability when applied to patients with VHD. These scores provide relatively good discrimination, i.e. a gross estimation of risk category, but cannot be used to estimate the exact operative mortality in an individual patient because of unsatisfactory calibration. CONCLUSION: Current risk scores do not provide a reliable estimate of exact operative mortality in an individual patient with VHD. They should therefore be interpreted with caution and only used as part of an integrated approach, which incorporates other patient characteristics, the clinical context, and local outcome data. Future risk scores should include additional variables, such as cognitive and functional capacity and be prospectively validated in high-risk patients. Specific risk models should also be developed for newer interventions, such as transcatheter aortic valve implantation.

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.