Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.).

Comprehensive care for people living with heart failure and chronic obstructive pulmonary disease-Integration of palliative care with disease-specific care: From guidelines to practice.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the leading global epidemiological, clinical, social, and economic burden. Due to similar risk factors and overlapping pathophysiological pathways, the coexistence of these two diseases is common. People with severe COPD and advanced chronic HF (CHF) develop similar symptoms that aggravate if evoking mechanisms overlap. The coexistence of COPD and CHF limits the quality of life (QoL) and worsens symptom burden and mortality, more than if only one of them is present. Both conditions progress despite optimal, guidelines directed treatment, frequently exacerbate, and have a similar or worse prognosis in comparison with many malignant diseases. Palliative care (PC) is effective in QoL improvement of people with CHF and COPD and may be a valuable addition to standard treatment. The current guidelines for the management of HF and COPD emphasize the importance of early integration of PC parallel to disease-modifying therapies in people with advanced forms of both conditions. The number of patients with HF and COPD requiring PC is high and will grow in future decades necessitating further attention to research and knowledge translation in this field of practice. Care pathways for people living with concomitant HF and COPD have not been published so far. It can be hypothesized that overlapping of symptoms and similarity in disease trajectories allow to draw a model of care which will address symptoms and problems caused by either condition.

Expert opinion of the Heart Failure Working Group of the Polish Cardiac Society on the use of dapagliflozin in the treatment of heart failure with reduced ejection fraction.

Heart failure (HF) is a global health problem inherent in an aging population with coexisting cardiovascular diseases. Based on data from the Polish National Health Fund (Polish, Narodowy Fundusz Zdrowia), approximately 1.2 million people in Poland currently suffer from HF, and 140 000 of them die annually. Recently, Poland was ranked fifth among the European Union countries regarding the number of patients with diagnosed HF and first in terms of the number of HF hospitalizations (547 per 100 000 population) among 34 countries associated in the Organization for Economic Cooperation and Development. In recent years, a significant progress has been made in the diagnosis and treatment of HF with reduced left ventricular ejection fraction (HFrEF), which has resulted in a reduction in cardiovascular and total mortality. Despite these advantages, 5-year survival in the course of HF is still worse than that observed in some types of cancer, both in the populations of men and women. Hence, the search for drugs improving the prognosis in this group of patients is still ongoing. Sodium-glucose cotransporter 2 inhibitors represent a new group of drugs that will undoubtedly be a milestone in the treatment of patients with HFrEF. This expert opinion covers the history of dapagliflozin, which, from a drug dedicated to the treatment of type 2 diabetes, has become one of the most effective drugs improving prognosis and quality of life as well as reducing the number of hospitalizations in patients with HF. This document presents the opinion from the experts of the Heart Failure Working Group of the Polish Cardiac Society on the most relevant studies on dapagliflozin and indications for its use.

Angiotensin receptor/neprilysin inhibitor-a breakthrough in chronic heart failure therapy: summary of subanalysis on PARADIGM-HF trial findings.

It is over 4 years since the Prospective Comparison of angiotensin receptor/neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial was published in New England Journal of Medicine. The PARADIGM-HF trial was the one that contributed to the official approval to use ARNI simultaneously with cardiac resynchronisation therapy (CRT) or implantable cardioverter-defibrillator (ICD) in patients who receive optimal medical treatment and still presented NYHA II-IV class symptoms according to the 2016 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure. The aim of this article is to summarise current knowledge on the activity of ARNI in a selected group of patients with heart failure with reduced ejection fraction (HFrEF) based on a recent PARADIGM-HF subanalysis in the field of renal function in patients with and without chronic kidney disease, glycaemia control in patients with diabetes, ventricular arrhythmias and sudden cardiac death and health-related quality of life. This article includes also recently announced findings on the TRANSITION study which revealed that HFrEF therapy with ARNI might be safely initiated after an acute decompensated heart failure episode, including patients with heart failure de novo and ACEI/ARB naïve, both hospitalised or shortly after discharge, in contrary to the PARADIGM-HF trial, where patients had to be administered a stable dose of an ACEI/ARB equivalent to enalapril 10 mg a day for at least 4 weeks before the screening.

Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study.

AIMS: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). METHODS AND RESULTS: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46). CONCLUSIONS: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02661217.

Diagnostic utility of biomarkers of left ventricular stress in patients with aortic stenosis and preserved left ventricular ejection fraction.

INTRODUCTION: Aortic stenosis (AS) is the most common acquired valvular heart disease. The early identification of patients with severe AS is crucial. NT-proBNP is a well-known biomarker of pressure overload, and its role in patients with AS has been demonstrated in previous studies. Another, less well-known biomarker of pressure overload is sST2 protein, and its role in AS is unclear. AIM: To evaluate the utility of sST2 protein, NT-proBNP and selected clinical parameters in the assessment of degenerative AS severity in a population with preserved left ventricular ejection fraction (LVEF). MATERIAL AND METHODS: Sixty-nine consecutive patients (mean age: 68.42 ±12.58 years, 55.07% male) with symptomatic degenerative AS and preserved LVEF ≥ 45% were prospectively included. At enrollment complete transthoracic echocardiographic examination, ECG analysis, and standard laboratory tests including NT-proBNP were performed and blood samples for sST2 were obtained. RESULTS: There were 43 (62.32%) patients with severe AS. The multivariate stepwise linear regression models revealed that only systolic blood pressure (SBP), Sokolow-Lyon index and left ventricular end-diastolic diameter (LVEDD) were independently associated with severe AS. Spearman correlation coefficients analysis showed no correlations between sST2 levels and a mild to moderate correlation between NT-proBNP concentration and parameters of AS severity. However, levels of NT-proBNP (p = 0.1857) and sST2 (p = 0.7851) did not differentiate patients according to severity of AS. CONCLUSIONS: In the study population with degenerative AS and preserved LVEF neither the NT-proBNP nor sST2 concentrations can be used to differentiate patients according to the severity of AS.

Thirty-year risk of cardiovascular disease in senior medical students - based on the StudHeart study.

INTRODUCTION: Long-term risk functions highlight the need of prophylaxis in youth before the first symptoms of cardiovascular disease (CVD) occur. AIM: On the basis of data obtained in the StudHeart study, the aim of this report was to evaluate the 30-year risk of CVD based on the risk scale developed by the Framingham Heart Study (FHS). MATERIAL AND METHODS: Seven hundred and one students aged 22-27 (mean age: 24 ±1.42) from the 5(th) and 6(th) year of the medical faculties of the Medical University of Lodz were included in the study. The StudHeart study was based on an anonymous survey comprising 12 questions. Based on the answers the authors evaluated the 30-year risk of CVD in each respondent using an on-line calculator that allows one to evaluate: general CVD risk including coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, heart failure and hard CVD risk including coronary death, myocardial infarction and stroke. RESULTS: Elevated general 30-year CVD risk occurred in 23.18% of students, while hard CVD risk was elevated in 16.91% of respondents. In both cases elevated risk occurred more often in men (general CVD risk: 43.46% male vs. 8.93% female, p < 0.001 and hard CVD risk: 29.33% male vs. 8.19% female, p < 0.001). Elevation of the risk was mainly caused by overweight, obesity and smoking cigarettes. CONCLUSIONS: Based on FHS 30-Year CVD risk, elevated risk occurred in almost one-fourth of students. Prophylactic actions should be performed, especially in men.

Fludrocortisone for the Prevention of Vasovagal Syncope: A Randomized, Placebo-Controlled Trial.

BACKGROUND: There is limited evidence whether being on fludrocortisone prevents vasovagal syncope. OBJECTIVES: The authors sought to determine whether treatment with fludrocortisone reduces the proportion of patients with recurrent vasovagal syncope by at least 40%, representing a pre-specified minimal clinically important relative risk reduction. METHODS: The multicenter POST 2 (Prevention of Syncope Trial 2) was a randomized, placebo-controlled, double-blind trial that assessed the effects of fludrocortisone in vasovagal syncope over a 1-year treatment period. All patients had >2 syncopal spells and a Calgary Syncope Symptom Score >-3. Patients received either fludrocortisone or matching placebo at highest tolerated doses from 0.05 mg to 0.2 mg daily. The main outcome measure was the first recurrence of syncope. RESULTS: The authors randomized 210 patients (71% female, median age 30 years) with a median 15 syncopal spells over a median of 9 years equally to fludrocortisone or placebo. Of these, 96 patients had ≥1 syncope recurrences, and only 14 patients were lost to follow-up before syncope recurrence. There was a marginally nonsignificant reduction in syncope in the fludrocortisone group (hazard ratio [HR]: 0.69: 95% confidence interval [CI]: 0.46 to 1.03; p = 0.069). In a multivariable model, fludrocortisone significantly reduced the likelihood of syncope (HR: 0.63; 95% CI: 0.42 to 0.94; p = 0.024). When the analysis was restricted to outcomes after 2 weeks of dose stabilization, there was a significant benefit due to fludrocortisone (HR: 0.51; 95% CI: 0.28 to 0.89; p = 0.019). CONCLUSIONS: The study did not meet its primary objective of demonstrating that fludrocortisone reduced the likelihood of vasovagal syncope by the specified risk reduction of 40%. The study demonstrated a significant effect after dose stabilization, and there were significant findings in post hoc multivariable and on-treatment analyses. (A randomised clinical trial of fludrocortisone for the prevention of vasovagal syncope; ISRCTN51802652; Prevention of Syncope Trial 2 [POST 2]; NCT00118482).

EuroSCORE II does not show better accuracy nor predictive power in comparison to original EuroSCORE: a single-centre study.

BACKGROUND: EuroSCORE is used to predict postoperative mortality in patients undergoing cardiac surgery. Its updated version was published in 2011. AIM: To assess whether EuroSCORE II (ESII) predicts more accurately postoperative mortality after cardiac surgery in comparison with additive (addES) and logistic EuroSCORE (logES). METHODS: A total of 461 patients (aged 21-88 years, 63.4% of men) who underwent cardiac surgery (December 2010 - June 2011) were included into the prospective research. For each patient ESII, addES and logES were calculated. Accuracy, calibration, and clinical performance of these models were assessed with receiver operating characteristics analyses using the area under the curve and the Hosmer-Lemeshow test. Out of this population, a group of 300 coronary artery bypass grafting (CABG) patients (aged 42-85 years, 73% of men) was selected and statistically analysed using the same methods. RESULTS: The mortality rate was 5.21%. Predicted mortality rates were as follows: addES 4.68%, logES 4.57%, and ESII 1.89%; the accuracy was: 0.589, 0.728, and 0.726, respectively. Only logES presented good predictive power (Hosmer-Lemeshow test: c2 = 12.79, p = 0.12). In the CABG patients, the postoperative mortality rate was 5.33%. Predicted mortality rates were as follows: addES 4.69%, logES 4.59%, and ESII 1.88%; the accuracy was: 0.512, 0.691, and 0.687, respectively. In the Hosmer-Lemeshow test also logES presented good predictive power (c2 = 10.72, p = 0.218). CONCLUSIONS: EuroSCORE II did not estimate mortality risk better in comparison to its previous versions, in the entire studied population or in the CABG patients. On the basis of the analysed data, it seems that the closest to the actual risk of death for the Polish population is the EuroSCORE logistic model.

New oral anticoagulants - a practical guide.

Oral direct inhibitors of thrombin and activated factor Xa are approved as new anticoagulant drugs. In contrast to vitamin K antagonists (VKA) and heparins, the new agents have single targets in the coagulation cascade and more predictable pharmacokinetics, but they lack validated and available antidotes. Unlike VKA, they do not require routine monitoring of coagulation. However, the measurement of their pharmacologic effects might be of value in selected patients. They interfere with the routine coagulation tests, which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. The administration of coagulation factors, such as fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII, can benefit in life-threatening bleeding or emergency surgery. Specific antidotes for non-vitamin K oral anticoagulants are in clinical development. This review aims at answering in a brief and simplified manner some clinical questions.

Severe multivessel coronary artery disease and high-sensitive troponin T.

INTRODUCTION: A key problem in stable coronary artery disease (CAD) is non-invasive identification of patients with severe multivessel CAD. Determination of biomarkers that have pro-inflammatory properties (C-reactive protein - hsCRP) and indicate heart muscle ischemia (high-sensitive troponin T - hsTnT) can contribute to the improvement of stratification in this regard. THE AIM OF THE STUDY: The aim of the study was to identify factors associated with the presence of multivessel CAD in clinically stable men. MATERIAL AND METHODS: The study included 92 symptomatic men (mean age 64.05 ± 9.42 years) with preserved left ventricular function, scheduled for elective coronary angiography. Patients were divided and analyzed in two groups: with multivessel coronary artery disease (2-3-vessel disease, n = 46) vs. without multivessel coronary artery disease (n = 46). RESULTS: Patients with multivessel CAD had significantly higher levels of hsTnT (0.01 vs. 0.007, p = 0.0021) and fasting glucose (6.0 vs. 5.45, p = 0.0112). Based on the drawn ROC curves, the cut-off points were determined for hsTnT ≥ 0.0085 ng/ml and fasting plasma glucose ≥ 5.85 mmol/l. From multivariate analysis only hsTnT in concentration higher than the cut-off point enhanced the risk of multivessel CAD (OR 4.286, 95% CI: 1.79-10.263, p = 0.001). CONCLUSIONS: In men with stable CAD, preserved systolic left ventricular function and non-high cardiovascular risk determined from the initial concentration of hsCRP, elevated level of hsTnT was independently associated with the risk of multivessel coronary artery disease.

Factors affecting the quality of anticoagulation with warfarin: experience of one cardiac centre.

INTRODUCTION: The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. MATERIAL AND METHODS: We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. RESULTS: The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). CONCLUSIONS: The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients.

Single sST2 protein measurement predicts adverse outcomes at 1-year follow-up in patients with chronic heart failure.

INTRODUCTION: sST2 protein is a new biomarker. Its prognostic value in chronic heart failure (CHF) is still unclear. OBJECTIVES: The aim of the study was to evaluate the value of sST2 protein in patients with CHF during 1-year follow-up after hospitalization for prediction of adverse events: cardiovascular death, rehospitalization, an increase in diuretic doses, and/or worsening of the New York Heart Association functional class, defined as the composite endpoint. PATIENTS AND METHODS: The study involved 145 consecutive patients (mean age, 62.16 ±11.25 y; men, 82.76%) with left ventricular (LV) ejection fraction of 30% or less and symptomatic CHF. We analyzed clinical and biochemical data along with the serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and sST2. The optimal cut-off points for significant predictors of the composite endpoint were determined using receiver operating characteristi c curves. RESULTS: Patients with elevated levels of sST2 and NT-proBNP had more than a 4-fold higher risk of composite endpoint (odds ratio [OR], 4.033; 95%CI, 1.540-10.559) compared with patients in whom both biomarkers were below the cut-off points. The C-statistic for predicting the composite endpoint was improved when both biomarkers were incorporated into the model (C-statistic, 0.692; P = 0.0001) compared with an individual analysis for NT-proBNP (C-statistic, 0.606; P = 0.009) and sST2 (C-statistic, 0.613; P = 0.003). Moreover, after the addition of sST2 to NT-proBNP, the continuous net reclassification improvement index (OR, 0.256; 95% CI, 0.090-0.401; P = 0.007) and the integrated discrimination improvement index (OR, 0.104; 95% CI 0.011-0.221; P = 0.007) significantly improved. CONCLUSIONS: A single measurement of sST2 levels on admission in patients with poor LV systolic function and stable CHF is useful in short-term risk stratification and, in combination with NT-proBNP, it could be more useful in identifying patients with unfavorable c ourse of CHF.

Truly low and high thromboembolic risk - impact of risk scores in real life.

BACKGROUND: Anticoagulation therapy is followed by analysis of factors used in the CHA2DS2-VASc score and assessing the risk of bleeding (HAS-BLED). THE AIM OF THE STUDY: The aim of the study was to evaluate in 'real life' risk stratification scores in nonvalvular atrial fibrillation (AF). MATERIAL AND METHODS: From 81 consecutive patients who had not yet received anticoagulation, 68 were finally enrolled after exclusion criteria. Patients were analyzed related to risk scores: CHADS2 ≥ 2 (group I) vs. CHADS2 < 2 and CHA2DS2-VASc score ≥ 2 (group II) and gender. Patients at high thromboembolic risk were treated with warfarin, after consideration of the patient's decision. RESULTS: At high risk of thromboembolic complications were 61 patients (90%). In 26 subjects (43%, 15 women - 57%) indication for anticoagulation was established by CHA2DS2-VASc. When compared to CHADS2 ≥ 2, these patients were younger (72 ±10 years vs. 63 ±10 years, p = 0.0002), less frequently burdened with arterial hypertension (p = 0.03) and had lower risk in HAS-BLED (1.23 ±0.65 vs. 0.81 ±0.49, p = 0.03). Seven patients (10%) did not require anticoagulation (CHA2DS2-VASc = 0). Compared to men, women more often had ischemic stroke (2 vs. 18%, p = 0.03), but less coronary artery disease (58 vs. 25%, p = 0.005). During 18 months on warfarin, bleeding occurred in 9 patients (13%, 6 women). On dual antiplatelet therapy were 11 patients (16%). No thromboembolic complications were recorded. CONCLUSIONS: CHA2DS2-VASc and HAS-BLED schemata easily identify real low and high thromboembolic risk patients and bleeding risk. It seems that women present higher risk of bleeding, but less frequent use of antiplatelet therapy.

The impact of chronic kidney disease on the annual prognosis in patients 80+ years old suffering from chronic heart failure.

INTRODUCTION: It is well known that the function of kidneys is impaired with age. AIM: The purpose of the study was to evaluate whether chronic kidney disease (CKD) is a predictor for 1-year follow-up mortality among hospitalized chronic heart failure (CHF) patients aged 80+. MATERIAL AND METHODS: The study included 141 consecutive patients aged 80-92 (mean: 82.4 years, 44.7% men). The prospective analysis contains 61 variables with glomerular filtration rate (GFR) and the occurrence of death at the 1-year follow-up. Patients were divided and analyzed depending on GFR. RESULTS: Chronic kidney disease defined as estimated GFR < 60 ml/min/1.73 m(2) was recorded in 93 patients (66%). A relationship with GFR < 60 was found for older age (p = 0.0001), lower body mass index - BMI (p = 0.003), more advanced NYHA class III (p = 0.007), higher concentrations of N-terminal probrain natriuretic peptide - NT-proBNP (p = 0.023), lower hemoglobin (p = 0.0004) and LVEF (p = 0.005), longer hospitalization (p = 0.005), more frequent ventricular blocks in ECG (p = 0.017) and rarely performed coronary angiography (p = 0.021). In turn, GFR < 30 ml/min/1.73 m(2) was recorded in 14 patients (9.9%). Similar relationships as in GFR < 60 were found for GFR < 30 and additionally higher concentrations of high-sensitivity C-reactive protein (hsCRP) (p = 0.003), D-dimer (p = 0.002) and more frequent dyslipidemia (p = 0.004) and left main coronary artery disease (p = 0.007). Annual mortality for the total population was 14.2% (n = 20) and was higher (16.1%) if GFR was < 60 and even more (21.4%) in GFR < 30. However, the relationship between deaths and GFR was not statistically significant (for GFR < 60, p = 0.505 and GFR < 30, p = 0.547). CONCLUSIONS: Annual mortality in the patients 80+ who suffered from CHF was high but not statistically significantly associated with CKD.

Giant aneurysm of the right coronary artery and magnetic resonance coronary angiography.

Coronary artery aneurysm (CAA) is generally defined as coronary dilatation that exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. The prime cause of CAAs is atherosclerosis, and the most commonly affected artery is the right coronary artery. CAAs are quite commonly detected during X-ray coronary angiography. However, Coronary artery aneurysm (CAA) is generally defined as coronary dilatation that exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. The prime cause of CAAs is atherosclerosis, and the most commonly affected artery is the right coronary artery. CAAs are quite commonly detected during X-ray coronary angiography. However, giant CAAs, especially with the diameter exceeding 100 mm, are extremely rare. The treatment method of choice of giant CAAs is the excision of aneurysm with coronary artery bypass grafting. We present a case of a 41-year-old apparently healthy woman with a giant right CAA. This was detected by noninvasive methods, including magnetic resonance coronary angiography, and its maximum diameter exceeded 100 mm. In emergency, the aneurysmal sac was excised and the aortocoronary saphenous vein graft was performed. We also present a review of the published studies of giant CAAs with the diameter exceeding 100 mm.