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.

Oral anticoagulation therapy in atrial fibrillation patients at high risk of bleeding: Clinical characteristics and treatment strategies based on data from the Polish multicenter register of atrial fibrillation (POL-AF).

BACKGROUND: Despite its benefits, oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF) is associated with hemorrhagic complications. AIMS: We aimed to evaluate clinical characteristics of AF patients at high risk of bleeding and the frequency of OAC use as well as identify factors that predict nonuse of OACs in these patients. METHODS: Consecutive AF patients hospitalized for urgent or planned reasons in cardiac centers were prospectively included in the registry in 2019. Patients with HAS-BLED ≥3 (high HAS-BLED group) were assumed to have a high risk of bleeding. RESULTS: Among 3598 patients enrolled in the study, 29.2% were at high risk of bleeding (44.7% female; median [Q1-Q3] age 72 [65-81], CHA2DS2-VASc score 5 [4-6], HAS-BLED 3 [3-4]). In this group, 14.5% of patients did not receive OACs, 68% received NOACs, and 17.5% VKAs. In multivariable analysis, the independent predictors of nonuse of oral OACs were as follows: creatinine level (odds ratio [OR], 1.441; 95% confidence interval [CI], 1.174-1.768; P <0.001), a history of gastrointestinal bleeding (OR, 2.918; 95% CI, 1.395-6.103; P = 0.004), malignant neoplasm (OR, 3.127; 95% CI, 1.332-7.343; P = 0.009), and a history of strokes or transient ischemic attacks (OR, 0.327; 95% CI, 0.166-0.642; P = 0.001). CONCLUSIONS: OACs were used much less frequently in the group with a high HAS-BLED score than in the group with a low score. Independent predictors of nonuse of OACs were creatinine levels, a history of gastrointestinal bleeding, and malignant neoplasms. A history of stroke or transient ischemic attack increased the chances of receiving therapy.

Lipid-Lowering Therapy after Acute Coronary Syndrome in Outpatient Practice-How to Achieve Goal.

BACKGROUND: Secondary prevention of cardiovascular disease involves the use of optimal pharmacological treatment and modification of risk factors through lifestyle changes. Recent evidence demonstrates that the major initiating event in atherogenesis is the storage of low-density lipoproteins. OBJECTIVES: We aimed to compare the efficacy in achieving the therapeutic lipid target in relation to the frequency of follow-up at selected time points and to determine the safety and tolerability of cholesterol-lowering drugs (statins, ezetimibe). METHODS: This was a prospective analysis of 72 consecutive patients hospitalized for acute coronary syndrome: ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Patients were consecutively divided into two groups: first, with follow-up and laboratory tests at 1, 3, 6 and 12 months after hospital discharge, including 32 patients; second, including 40 patients with follow-up and laboratory tests 12 months after hospital discharge. RESULTS: A significant reduction in LDL-C level was observed at 12 months in both groups. LDL-C level was significantly lower in group 1 than in group 2 after 12 months (p = 0.02). Total cholesterol level was significantly lower in group 1 than in group 2 after 12 months. After 12 months of therapy, 21 (65.6%) patients in group 1 and 17 (42.5%) in group 2 had LDL-C < 1.4 mmol/L. In group 1, we observed a significant decrease in LDL-C, triglyceride, and total cholesterol levels at 1, 3, 6 and 12 months (p < 0.05). CONCLUSIONS: The group of patients with more frequent follow-up visits showed a greater reduction in LDL-C level than the group with only one visit after a 12-month hospital discharge.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Anatomic Variations of Renal Arteries as an Important Factor in the Effectiveness of Renal Denervation in Resistant Hypertension.

Hypertension remains the leading cause of death worldwide. Despite advances in drug-based treatment, many patients do not achieve target blood pressure. In recent years, there has been an increased interest in invasive hypertension treatment methods. Long-term effects and factors affecting renal denervation effectiveness are still under investigation. Some investigators found that the renal arteries' morphology is crucial in renal denervation effectiveness. Accessory renal arteries occur in 20-30% of the population and even more frequently in patients with resistant hypertension. Diversity in renal vascularization and innervation may complicate the renal denervation procedure and increase the number of people who will not benefit from treatment. Based on previous studies, it has been shown that the presence of accessory renal arteries, and in particular, the lack of their complete denervation, reduces the procedure's effectiveness. The following review presents the anatomical assessment of the renal arteries, emphasizing the importance of imaging tests. Examples of imaging and denervation methods to optimize the procedure are presented. The development of new-generation catheters and the advancement in knowledge of renal arteries anatomy may improve the effectiveness of treatment and reduce the number of patients who do not respond to treatment.

Neutrophil-activating Peptide 2 as a Novel Modulator of Fibrin Clot Properties in Patients with Atrial Fibrillation.

Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF). We recruited 237 consecutive patients with AF (mean age, 68 ± 11 years; median CHA2DS2VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (> 796 ng/ml) were characterized by higher neutrophil count (+ 31.7%), fibrinogen (+ 20.8%), citH3 (+ 86%), and 3-nitrotyrosine (+ 111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1 ng/ml ß = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100 ng/ml ß = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced Ks. Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF.

Three-dimensional cardiac computed tomography compared with autopsied material for the assessment of the mitral valve.

To compare the morphometrical features of non-diseased mitral valves imaged in three-dimensional (3D) cardiac computed tomography with those analyzed macroscopically in autopsied healthy human hearts. A total of 51 cardiac computed tomography scans and 120 adult autopsied human hearts without cardiovascular disease were examined. The 3D reconstruction and visualization software (Mimics Innovation Suite 22, Materialise) was used for heart chambers semi-automatic segmentation and myocardial manual segmentation to visualize a 3D structure of the mitral valve complex and to perform all measurements. Direct comparison of corresponding mitral valve parameters revealed significant differences between obtained results. Significantly larger intercommisural diameter, aorto-mural diameter, and perimeter of the mitral annulus were observed in tomographic scans (all p < 0.0001). However, the intercommissural/aorto-mural diameter ratio showed comparable values for both groups. Nevertheless, the size of anterior mitral leaflet was higher in autopsied material. The height of the P2 scallops was the only parameter that show no significant difference between two groups (p = 0.3). The use of 3D postprocessing algorithms provides a very accurate image of the mitral valve structure, which could be useful for the precise non-invasive assessment of mitral valve size and structure. Three-dimensional contrast enhanced cardiac computed tomography significantly overestimates the measurements of the mitral annulus compared to postmortem analysis.

Do Patients with Atrial Fibrillation and a History of Ischemic Stroke Overuse Reduced Doses of NOACs?-Results of the Polish Atrial Fibrillation (POL-AF) Registry.

BACKGROUND: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). METHODS: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. RESULTS: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use-out of reduced dosage groups, p = 0.06). CONCLUSIONS: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.

Effectiveness and safety of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with familial hypercholesterolemia. Our experience in implementing the drug program of the Polish National Health Fund.

Introduction: Heterozygous familial hypercholesterolemia (FH) is characterized by an elevated plasma low-density lipoprotein cholesterol (LDL-C) concentration despite intensive statin and ezetimibe therapy, which significantly increases the cardiovascular risk. Aim: The study evaluated the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, in reducing lipids in patients with FH. Material and methods: This was a single-center analysis of 22 patients diagnosed with FH treated with the PCSK9 inhibitors under the drug program of the National Health Fund. The follow-up interviews and laboratory tests were performed at baseline (22 patients), 3 months (22 patients) and 15 months (9 patients) after the first dose of PCSK9 inhibitors. Results: The mean (SD) baseline level of the total LDL-C fraction was 4.7 ±1.6 mmol/l in the whole group of patients and was significantly reduced after 3 and 15 months of PCSK9 inhibitors therapy to 1.7 ±1.6 and 1.6 ±1.1 mmol/l, respectively. The average percentage of reduction in LDL-C level was 64.9 ±23.7% after 3 months and 66.9 ±18.4% after 15 months. In comparison with baseline, a significant reduction in total cholesterol was observed at both time points (p <0.0002). There were no adverse cardiovascular events or significant growth in the level of alanine transaminase, creatinine, and creatine kinase throughout the study. Conclusions: Patients with FH treated with PCSK9 inhibitors achieved a significant reduction of LDL-C and total cholesterol with the safety of this treatment in follow-up.

Association of Hyperuricemia with Impaired Left Ventricular Systolic Function in Patients with Atrial Fibrillation and Preserved Kidney Function: Analysis of the POL-AF Registry Cohort.

Hyperuricemia is associated with the risk of developing atrial fibrillation (AF) and heart failure. However, coexisting chronic kidney disease and certain cardiovascular drugs make it difficult to determine whether hyperuricemia is a risk factor or merely a marker of pathology. We retrieved data from the Polish Atrial Fibrillation (POL-AF) registry, which included consecutive patients hospitalized with AF from January to December, 2019. We included 829 patients (mean age: 72.7 ± 11.1 years) with data on serum uric acid (UA, mean: 6.56 ± 1.78 mg/dL) and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. We found that UA and ejection fraction (EF) were significantly correlated (r = −0.15, p < 0.05), but not EF and eGFR or eGFR and UA. A multiple regression analysis adjusted for age, body mass index, eGFR, and UA, showed that UA was significantly associated with a reduced EF (R2: 0.021; p < 0.001). The UA cut-off indicative of an EF < 40% was 6.69 mg/dL (AUC, area under the curve: 0.607; 95% CI: 0.554−0.660; p = 0.001). Among drugs known to effect UA concentrations, we found that only diuretics were used more frequently in patients with high UA (above the median) than in patients with low UA (77.5% vs. 67%, p < 0.001). Among patients that used diuretics, UA remained significantly correlated with EF. Thus, we showed that reduced EF was associated with UA in patients with AF and normal renal function, independent of eGFR and diuretic use.

Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

BACKGROUND: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). METHODS: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). RESULTS: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. CONCLUSIONS: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

Why Did All Patients with Atrial Fibrillation and High Risk of Stroke Not Receive Oral Anticoagulants? Results of the Polish Atrial Fibrillation (POL-AF) Registry.

BACKGROUND: Most atrial fibrillation (AF) patients are at high risk of thromboembolic, and the use of oral anticoagulants (OACs) is advised in such cases. The aim of the study was to evaluate the frequency at which OACs were used in patients with AF and high risk thromboembolic complications, and identify factors that result in OACs not being used in the researched group of patients. METHODS: The prospective, multicenter and non-interventional POL-AF registry is a study that includes AF patients from ten Polish cardiology centers. They were consecutively hospitalized between January and December of 2019. All the patients in the study were of high stroke risk. RESULTS: A total of 3614 patients with AF and high stroke risk were included. Among the total study population, 91.5% received OAC therapy; antiplatelet therapy was prescribed for 3.7% of patients, heparin for 2.7%, and 2.1% of patients did not receive any stroke prevention therapy. Independent predictors of no OAC prescription were intracranial bleeding (OR 0.15, 95%CI 0.07-0.35, p < 0.001), gastrointestinal bleeding (OR 0.25, 95%CI 0.17-0.37, p < 0.001), cancer (OR 0.37, 95%CI 0.25-0.55, p < 0.001), hospitalization due to acute coronary syndrome (OR 0.48, 95%CI 0.33-0.69, p < 0.001), and anemia (OR 0.62, 95%CI 0.48-0.81, p < 0.001). CONCLUSIONS: Most AF patients with a high thromboembolic risk received OACs. The factors predisposing a lack of OAC use in these patients were conditions that significantly increased the risk of bleeding complications.

Mavacamten - a new disease-specific option for pharmacological treatment of symptomatic patients with hypertrophic cardiomyopathy.

Current pharmacotherapy for hypertrophic cardiomyopathy (HCM) is not disease-specific and has suboptimal efficacy, often necessitating interventional treatment. EXPLORER-HCM was a phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial investigating the effects of mavacamten, a first-in-class selective cardiac myosin inhibitor, in patients with HCM, left ventricular outflow tract obstruction (LVOTO) and New York Heart Association (NYHA) class II or III symptoms. The primary endpoint was defined as either a ≥1.5 ml/kg/min increase in peak oxygen consumption (pVO2) and ≥1 NYHA class reduction or a ≥3.0 ml/kg/min pVO2 increase without NYHA class worsening. Secondary endpoints evaluated changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopa-thy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). A total of 251 patients were randomized to receiving mavacamten or placebo. The primary endpoint and all secondary endpoints were met significantly more frequently in the mavacamten arm versus placebo. The safety profile of mavacamten was similar to that of placebo. In conclusion, disease-specific treatment with mavacamten in patients with obstructive HCM led to reduced LVOTO and improvement in both objective functional parameters and patient-related health status.