Comparison of the population of Polish patients participating in the TRANSITION study with the international population: a post hoc analysis.

INTRODUCTION: Heart failure (HF) patients discharged from a hospital are at a high risk of death and rehospitalization. Scarce data are available on the use of sacubitril / valsartan in this population in Poland. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of sacubitril / valsartan in the group of Polish patients who participated in the TRANSITION study with the patients recruited at other sites. PATIENTS AND METHODS: This is a post hoc secondary analysis of the TRANSITION study comparing sacubitril / valsartan initiation pre- vs postdischarge in 991 patients hospitalized for acute decompensated HF with reduced ejection fraction (HFrEF). The Polish subgroup consisted of 104 patients. RESULTS: Significant differences were identified in the characteristics of Polish vs non­Polish populations. At baseline, the Polish population showed higher proportion of men, higher body mass index, lower heart rate, N­terminal pro-B­type natriuretic peptide and high­sensitivity troponin T levels, and significantly lower New York Heart Association class. The Polish patients were better managed in terms of implanted electrotherapy devices, percutaneous coronary interventions, and drug therapy, and were more often hospitalized. The primary end point of achieving the target dose of sacubitril / valsartan at treatment week 10 was met by 45.6% of the Polish patients and 48.4% of the non­Polish population (P = 0.61). Approximately 90% of the Polish patients received and maintained any sacubitril / valsartan dose for 2 weeks over 10­week treatment vs 87.5% of the non­Polish patients (P = 0.36). The rate of permanent sacubitril / valsartan treatment discontinuation was low in both Polish (3.9%) and non­Polish populations (6.4%) (P = 0.33). CONCLUSIONS: Sacubitril / valsartan can be used safely in the early period after an episode of acute HF both in the Polish and non­Polish patients with HFrEF, and the likelihood to achieve the maximum dose is the same despite significant differences between the studied populations.

Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database.

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25-30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality.

ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH. METHODS: The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed. RESULTS: P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO2 slope; r = 0.436, p = 0.029) and echocardiographic estimated RA pressure (RAP; r = 0.504, p = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload-tricuspid regurgitation pressure gradient (TRPG; r = 0.788, p < 0.001), RV free wall thickness (r = 0.738, p < 0.001), and mean pulmonary arterial pressure (mPAPECHO; r = 0.62, p = 0.0016), respectively, as well as VE/VCO2 slope (r = 0.593, p = 0.001) and mPAP assessed directly in RHC (mPAPRHC; r = 0.469, p = 0.0497). R-wave in lead aVR correlated positively with TRPG (r = 0.719, p < 0.001), mPAPECHO (r = 0.446, p = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAPRHC (r = 0.505, p = 0.033) and pulmonary vascular resistance (r = 0.554, p = 0.026) and negatively with pulmonary capillary wedge pressure (r = -0.646, p = 0.004). QRS duration correlated positively with estimated RAP (r = 0.589, p = 0.004), vena cava inferior diameter (r = 0.506, p = 0.016), and RA area (r = 0.679, p = 0.002) and negatively with parameters of exercise capacity: peak VO2 (r = -0.486, p = 0.012), CPET maximum load (r = - 0.439, p = 0.025), and 6-MWT distance (r = -0.430, p = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors. CONCLUSION: Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity.

IGFBP7 Concentration May Reflect Subclinical Myocardial Damage and Kidney Function in Patients with Stable Ischemic Heart Disease.

The objective of this study was to determine the associations between insulin-like growth-factor-binding protein 7(IGFBP7) concentrations and concentrations of troponin T(TnT), N-terminal pro-B-type natriuretic peptide(NT-proBNP) and the parameters of kidney function in patients with stable ischemic heart disease(IHD). The IHD group consisted of 88 patients, and the population group comprised 66 subjects without a history of IHD. IGFBP7, TnT and NTproBNP concentrations were measured. The IGFBP7 value was considerably higher in the IHD group (1.76 ± 1 ng/mL vs. 1.43 ± 0.44 ng/mL, respectively, p = 0.019). Additionally, IHD subjects had a significantly higher concentration of TnT and NTproBNP. In both groups there was a significant correlation between IGFBP7 and serum parameters of kidney function (creatinine concentration: population gr. r = 0.45, p < 0.001, IHD gr. r = 0.86, p < 0.0001; urea concentration: population gr. r = 0.51, p < 0.0001, IHD gr. r = 0.71, p < 0.00001). No correlation between IGFBP7 and microalbuminuria or the albumin to creatinine ratio in urine was found. Moreover, there was a significant correlation between IGFBP7 concentration and markers of heart injury/overload-TnT and NT-BNP(r = 0.76, p < 0.001 and r = 0.72, p < 0.001, respectively). Multivariate regression analysis in joint both revealed that the IGFBP7 concentration is independently associated with urea, creatinine and TnT concentrations (R2 for the model 0.76). IHD patients presented significantly higher IGFBP7 concentrations than the population group. Elevated IGFBP7 levels are associated predominantly with markers of kidney function and myocardial damage or overload.

Monocyte Subsets in Patients with Chronic Heart Failure Treated with Cardiac Resynchronization Therapy.

BACKGROUND: The exact role of individual inflammatory factor in heart failure with reduced ejection fraction (HFrEF) remains elusive. The study aimed to evaluate three monocyte subsets (classical-CD14++CD16-, intermediate-CD14++CD16+, and nonclassical-CD14+CD16++) in HFrEF patients and to assess the effect of the cardiac resynchronization therapy (CRT) on the changes in monocyte compartment. METHODS: The study included 85 patients with stable HFrEF. Twenty-five of them underwent CRT device implantation with subsequent 6-month assessment. The control group consisted of 23 volunteers without HFrEF. RESULTS: The analysis revealed that frequencies of non-classical-CD14+CD16++ monocytes were lower in HFrEF patients compared to the control group (6.98 IQR: 4.95-8.65 vs. 8.37 IQR: 6.47-9.94; p = 0.021), while CD14++CD16+ and CD14++CD16- did not differ. The analysis effect of CRT on the frequency of analysed monocyte subsets 6 months after CRT device implantation showed a significant increase in CD14+CD16++ (from 7 IQR: 4.5-8.4 to 7.9 IQR: 6.5-9.5; p = 0.042) and CD14++CD16+ (from 5.1 IQR: 3.7-6.5 to 6.8 IQR: 5.4-7.4; p = 0.017) monocytes, while the frequency of steady-state CD14++CD16- monocytes was decreased (from 81.4 IQR: 78-86.2 to 78.2 IQR: 76.1-81.7; p = 0.003). CONCLUSIONS: HFrEF patients present altered monocyte composition. CRT-related changes in the monocyte compartment achieve levels observed in controls without HFrEF.

Effectiveness and safety of a simple home-based rehabilitation program in pulmonary arterial hypertension: an interventional pilot study.

BACKGROUND: Rehabilitation plays an important role in the management of patients with pulmonary arterial hypertension (PAH) and current guidelines recommend implementation of a monitored individualized exercise training program as adjuvant therapy for stable PAH patients on optimal medical treatment. An optimal rehabilitation model for this group of patients has not yet been established. This randomized prospective study assessed the effectiveness and safety of a 6-month home-based caregiver-supervised rehabilitation program among patients with pulmonary arterial hypertension. METHODS: A total of 39 patients with PAH were divided into two groups: intervention group (16 patients), subjected to a 6-month home-based physical training and respiratory rehabilitation program adapted to the clinical status of participants, and control group (23 patients) who did not perform physical training. The 6-min walk test (6MWT), measurement of respiratory muscle strength, quality of life assessment (SF-36, Fatigue Severity Scale - FSS) were performed before study commencement, and after 6 and 12 months. Adherence to exercise protocol and occurrence of adverse events were also assessed. RESULTS: Physical training significantly improved 6MWT distance (by 71.38 ± 83.4 m after 6 months (p = 0.004), which remained increased after 12 months (p = 0.043), and respiratory muscle strength after 6 and 12 months (p < 0.01). Significant improvement in quality of life was observed after the training period with the use of the SF-36 questionnaire (Physical Functioning, p < 0.001; Role Physical, p = 0.015; Vitality, p = 0.022; Role Emotional, p = 0.029; Physical Component Summary, p = 0.005), but it did not persist after study completion. Adherence to exercise protocol was on average 91.88 ± 14.1%. No serious adverse events were noted. CONCLUSION: According to study results, the home-based rehabilitation program dedicated to PAH patients is safe and effective. It improves functional parameters and quality of life. Strength of respiratory muscles and 6MWD remain increased 6 months after training cessation. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03780803 . Registered 12 December 2018.

Echocardiographic Assessment of Right Ventricular-Arterial Coupling in Predicting Prognosis of Pulmonary Arterial Hypertension Patients.

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular-arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients.

Characteristics and outcomes of patients with chronic thromboembolic pulmonary hypertension in the era of modern therapeutic approaches: data from the Polish multicenter registry (BNP-PL).

BACKGROUND: Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact of the changed landscape of CTEPH therapies on patients' management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies. METHODS: We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry. RESULTS: We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants (n = 301; 58.3%) were preferred over vitamin K antagonists (n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment. CONCLUSIONS: The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT03959748.

Impact of Pulse Wave Velocity and Parameters Reflecting Android Type Fat Distribution on Left Ventricular Diastolic Dysfunction in Patients with Chronic Coronary Syndromes.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is caused by a decreased left ventricle relaxation and is associated with an increased risk of symptomatic heart failure (HF) and excessive mortality. AIM: To evaluate the frequency and factors related to LVDD in the population with chronic coronary syndromes (CCS). METHODS: 200 patients (mean age 63.18 ± 8.12 years, 75.5% male) with CCS were included. LVDD was diagnosed based on the recent echocardiography guidelines. RESULTS: LVDD was diagnosed in 38.5% of CCS population. From the studied factors, after adjustment for age, sex, and N-terminal pro-brain natriuretic peptide (NT-proBNP), LVDD associated positively with android/gynoid (A/G) fat mass ratio, left ventricular mass index (LVMI), and negatively with Z-score and left ventricular ejection fraction (LVEF). In stepwise backward logistic regression analysis, the strongest factors associated with LVDD were pulse wave velocity value, handgrip strength and waist to hip ratio (WHR). CONCLUSIONS: LVDD is common among CCS patients and it is associated with parameters reflecting android type fat distribution regardless of NT-proBNP and high-sensitivity troponin T concentrations. Deterioration in diastolic dysfunction is linked with increased aortic stiffness independently of age and sex. Further studies evaluating the effects of increasing physical fitness and lowering abdominal fat accumulations on LVDD in CCS patients should be considered.

Defining right ventricular dysfunction by echocardiography in normotensive patients with pulmonary embolism.

INTRODUCTION: Although the prognostic value of various echocardiographic parameters of right ventricular dysfunction (RVD) was reported in normotensive patients with acute pulmonary embolism (PE), there is no generally accepted definition of RVD. OBJECTIVES: The aim of the study was to compare echocardiographic parameters for the prediction of an adverse 30­day outcome and create an optimal definition of RVD.                                     Patients and methods: Echocardiographic parameters including the right ventricular to left ventricular diameter ratio (RV to LV ratio) and tricuspid annular plane systolic excursion (TAPSE) to predict PE­related mortality, hemodynamic collapse, or rescue thrombolysis within the first 30 days were directly compared in 490 normotensive patients with PE. RESULTS: An adverse outcome (AO) was present in 31 patients (6.3%); 8 of them (1.6%) died due to PE. Systolic blood pressure, RV to LV ratio, and TAPSE were independent predictors of AO. The receiver operator characteristic yielded an area under the curve of 0.737 (0.654-0.819; P <0.001) for the RV to LV ratio and 0.75 (0.672-0.828; P <0.001) for TAPSE with regard to an AO. The hazard ratio for AO was 2.5 for the RV to LV ratio of more than 1 (95% CI, 1.2-5.7; P <0.03) and 3.8 for TAPSE of less than 16 mm (95% CI, 1.74-8.11; P = 0.001). A combined RVD criterion (TAPSE <16 mm and RV to LV ratio >1) was present in 60 patients (12%), and showed a positive predictive value of 23.3% with a high negative predictive value of 95.6% regarding an AO (HR, 6.5; 95% CI, 3.2-13.3; P <0.001). CONCLUSIONS: Defining RVD on echocardiography by the RV to LV ratio of more than 1 combined with TAPSE of less than 16 mm identified patients with an increased risk of 30­day PE­related mortality, hemodynamic collapse, or rescue thrombolysis, while patients without this sign had a very good 30­day prognosis.

Galectin-3 as the Prognostic Factor of Adverse Cardiovascular Events in Long-Term Follow up in Patients after Myocardial Infarction-A Pilot Study.

Galectin-3 (Gal-3) is a new independent risk factor in the development and severity of coronary artery disease (CAD). The aim of the study was to evaluate whether Gal-3 concentration has prognostic value and if it reflects the progression of atherosclerosis in carotid arteries in patients with CAD after acute myocardial infarction (AMI). The analysis included 110 patients who were hospitalized due to AMI, treated with primary coronary intervention (PCI) and further attended a follow-up visit, and 100 healthy volunteers. The Gal-3 concentration and carotid ultrasound were evaluated at baseline and on a follow-up visit. We found that the Gal-3 concentration in the group with hyperlipidemia decreased during the observation (10.7 vs. 7.9 ng/mL, p = 0.00003). Patients rehospitalized during follow up had higher concentration of Gal-3 in the acute phase of myocardial infarction (MI) (10.7 vs. 7.2 ng/mL, p = 0.02; 10.1 vs. 8.0 ng/mL, p = 0.002, respectively). In the group of patients who had none of the following endpoints: subsequent MI, PCI, coronary artery bypass grafting (CABG) or stroke, there was a decrease in Gal-3 concentration at the follow-up visit. Parameters affecting the frequency of a composite endpoint occurrence are: the presence of atheromatous plaque in the carotid artery (p = 0.017), Gal-3 (p = 0.004) and haemoglobin (p = 0.03) concentration. In multivariate analysis, only Gal-3 concentration higher than 9.2 ng/mL at discharge was associated with a nine-fold increase of risk of composite endpoint occurrence (p = 0.0005, OR = 9.47, 95% CI 2.60-34.45). A significant decrease in Gal-3 concentration was observed in the group of patients after AMI without the endpoint occurrence during observation.

ECG Indices Poorly Predict Left Ventricular Hypertrophy and Are Applicable Only in Individuals With Low Cardiovascular Risk.

Background: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular events. The electrocardiography (ECG) has poor sensitivity, but it is commonly used to detect LVH. AIM: To evaluate the diagnostic efficacy of known ECG indicators to recognize LVH in subgroups with different cardiovascular risk levels. Methods: 676 volunteers were included. RESULTS: We found that 10.2% of the analyzed population had LVH based on echocardiography. Individuals with LVH were older, had a higher body mass index, higher systolic blood pressure, lower heart rate, higher parameters of insulin resistance, higher cardiovascular risk, and android-type obesity. Variables that remained independently associated with LVH were QRS duration, left atrial volume index, troponin T, and hemoglobin A1c. The receiver operating characteristics (ROC) curve analysis of the Sokolow-Lyon index did not show a significant predictive ability to diagnose LVH in the whole study population including all cardiovascular risk classes. The ROC curves analysis of Cornell and Lewis indices showed a modest predictive ability to diagnose LVH in the general population and in a low cardiovascular class. CONCLUSIONS: There is a need for new, simple methods to diagnose LVH in the general population in order to properly evaluate cardiovascular risk and introduce optimal medical treatment of concomitant disease.

Characterization of Patients with Pulmonary Arterial Hypertension: Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

Current knowledge of pulmonary arterial hypertension (PAH) epidemiology is based mainly on data from Western populations, and therefore we aimed to characterize a large group of Caucasian PAH adults of Central-Eastern European origin. We analyzed data of incident and prevalent PAH adults enrolled in a prospective national registry involving all Polish PAH centers. The estimated prevalence and annual incidence of PAH were 30.8/mln adults and 5.2/mln adults, respectively and they were the highest in females ≥65 years old. The most frequent type of PAH was idiopathic (n = 444; 46%) followed by PAH associated with congenital heart diseases (CHD-PAH, n = 356; 36.7%), and PAH associated with connective tissue disease (CTD-PAH, n = 132; 13.6%). At enrollment, most incident cases (71.9%) were at intermediate mortality risk and the prevalent cases had most of their risk factors in the intermediate or high risk range. The use of triple combination therapy was rare (4.7%). A high prevalence of PAH among older population confirms the changing demographics of PAH found in the Western countries. In contrast, we found: a female predominance across all age groups, a high proportion of patients with CHD-PAH as compared to patients with CTD-PAH and a low use of triple combination therapy.

Chemokines profile in patients with chronic heart failure treated with cardiac resynchronization therapy.

PURPOSE: Inflammatory mechanisms have been suggested to play a role in the heart failure with reduced ejection fraction (HF-REF) development, but the role of chemokines is largely unknown. Cardiac resynchronization therapy (CRT) may reverse the HF-REF course. We aimed to evaluate selected chemokines concentrations in HF-REF patients and their relationship with disease severity and clinical response to CRT. MATERIALS AND METHODS: The study included 37 patients (64.1 ± 11.04 years, 6 females) with HF-REF subjected to CRT, controlled prior to implantation and after 6 months. The control population included 26 healthy volunteers (63.9 ± 8.1 years, 8 females). Serum chemokines concentrations were determined using multiplex method. RESULTS: HF-REF patients were characterized by the higher baseline MIF, NAP-2 and PF4 concentrations and lower Axl, BTC, IL-9, and IL-18 BPa concentrations comparing to controls. After 6 months of CRT only NAP-2 concentration decreased significantly in comparison to the baseline values. CONCLUSIONS: HF-REF patients present altered chemokines profile compared to the control group. The CRT-related alleviation of HF-REF causes only slight changes in the chemokines concentrations especially in the platelet-associated ones. The precise chemokines role in the HF-REF pathogenesis and their prognostic value remains to be established.

Treatment of chronic thromboembolic pulmonary hypertension in a multidisciplinary team.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) may be treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapy (MT). Assessment in a multidisciplinary team of experts (CTEPH team) is currently recommended for treatment decision making. The aim of the present study was to report the effects of such an interdisciplinary concept. METHODS AND RESULTS: A total of 160 patients were consulted by the CTEPH team between December 2015 and September 2018. Patient baseline characteristics, CTEPH team decisions and implementation rates of diagnostic and therapeutic procedures were analysed. Change in World Health Organization (WHO) functional class and survival rates were evaluated by treatment strategy. A total of 51 (32%) patients were assessed as operable and 109 (68%) were deemed inoperable. Thirty-one (61% of operable patients) underwent PEA. Patients treated with PEA, BPA(+MT) and MT alone were 50.9 ± 14.7, 62.9 ± 15.1 and 68.9 ± 12.7 years old, respectively. At the follow-up, PEA patients had the highest WHO functional class improvement. Patients treated with BPA(+MT) had significantly better survival than PEA (p = 0.04) and MT patients (p = 0.04; 2-year survival of 92%, 79% and 79%, respectively). CONCLUSIONS: The CTEPH team ensures that necessary diagnostic procedures are performed. A relatively low proportion of patients was assessed by the CTEPH team as operable and underwent surgery, which in survivors resulted in the best functional improvement. Although patients undergoing BPA(+MT) were older than patients treated with PEA, their survival was better than patients subjected to PEA or MT alone. The reviews of this paper are available via the supplemental material section.

Atrial Fibrillation in Patients with Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis.

Pulmonary embolism (PE) is one of the most common causes of cardiovascular death. The most often PE etiology is a deep vein thrombosis (DVT) of the lower extremities, but embolic material can arise in pelvic or upper extremity veins as well as in right heart chambers. There is growing number of evidences of atrial fibrillation (AF) involvement in PE. The presence of AF in patients with PE may be both the cause and the consequence of PE. The PE association with AF should be considered in patients without confirmed DVT and with history of AF, which itself is associated with prothrombotic state. The valuable diagnostic method is echocardiography that may bring the insight into source of embolic material. Another possible AF and PE association is the AF as a consequence of an abrupt increase in pulmonary vascular resistance due to the occlusion of the pulmonary vessels. Large-scale population-based studies have provided a considerable body of evidence on the involvement of PE in the onset of subsequent AF. Another important issue is the influence of AF on prognosis in patients with PE. Most investigators demonstrated a negative impact of AF on mortality. The main problem to resolve is whether AF is an independent mortality risk factor or whether it occurs as a result of comorbidities or the severity of a PE episode. Although the pathophysiological basis of this bidirectional relationship exists, many questions are still unresolved and require further studies, including the significance of paroxysmal AF accompanying an acute PE episode, the usefulness of PE risk scales in patients with concomitant AF, and the effect of anticoagulant treatment on PE and AF occurrence. Regardless of the type of AF, clinicians should be alert to the possibility of PE in patients with previous history of AF or presenting with new-onset AF.

Increased platelet content of SDF-1alpha is associated with worse prognosis in patients with pulmonary prterial hypertension.

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.85*10-10 [0.29 - 1.37] vs. 0.45*10-10 [0.19-0.65], sIL-6R 1.54*10-7 [1.32-2.21] vs. 1.14*10-7 [1.01-1.28] and SDF-1 (2.72*10-7 [1.85-3.23] vs. 1.70*10-7 [1.43-2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.68*10-7 [2.45-4.62] vs. 1.69*10-7 [1.04-2.28], p = 0.001), with no significant differences between plasma levels. Kaplan-Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation.

The significance of diminished sTWEAK and P-selectin content in platelets of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative changes in pulmonary arteries. There is growing evidence suggesting that soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and P-selectin could be involved in PAH development and progression. Here we investigate whether circulating platelets may be a source of sTWEAK and contribute to diminished availability of sTWEAK and P-selectin in PAH patients. We have prospectively enrolled two independent study groups of stable patients with confirmed PAH and age matched controls: derivation (10 PAH; 15 controls) and validation (20 PAH; 12 controls). P-selectin and sTWEAK concentrations were measured in platelet-poor plasma and platelet lysate. To avoid procedural bias, in each group we employed different protocols for platelet isolation. Consistently, both in derivation and validation groups PAH patients presented significantly lower sTWEAK content in platelets than control group with no significant differences in plasma levels. Similarly, patients presented comparable to controls plasma P-selectin concentrations and lower concentration in platelet lysate. Kaplan-Meier analysis revealed that patients with low platelet sTWEAK/total protein concentration ratio had more frequently detoriation of PAH in the follow-up (16.51 ±â€¯3.32 months), log-rank test, p = .03. Patients diagnosed with pulmonary arterial hypertension present diminished sTWEAK and P-selectin storage capacity in platelets. Thrombocytes appear to be a major source of sTWEAK that could be released upon local injury and its decreased availability could have an impact on pathophysiology and prognosis in PAH.

Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy.

INTRODUCTION: Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects. MATERIAL AND METHODS: The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits. RESULTS: The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6-3.8 vs. 2.1, IQR: 1.4-3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36-64 vs. 53. IQR 44-76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF (r = -0.5, p = 0.001) and positively with BNP (r = 0.5, p = 0.008) and CRP concentrations (r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: -0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04). CONCLUSIONS: HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients' functional status is associated with a smaller change of sIL-6R concentration in time.