Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology.

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Demographical and Clinical Factors Predictive for Aortic Dilatation. When should we be Concerned about the Size?

Background: Thoracic aortic aneurysms are often an accidental finding and result from a degenerative process. Medical therapy includes pharmacological control of arterial hypertension and smoking cessation, that slows the growth of aneurysms. An association between the dilatation of the ascending and abdominal aorta has been already reported. The aim of the study was to identify possible demographic and clinical factors that may implicate further imaging diagnostics in patients with ascending aorta dilatation. Methods: There were 181 (93 (53%) males and 88 (47%) females) patients with a median age of 54 (41-62) years who underwent cardiac magnetic resonance due to non-vascular diseases, were enrolled into retrospective analysis. Results: Multivariable analysis revealed ascending aorta dilatation (odds ratios (OR) = 7.45, 95% confidence interval (CI): 1.98-28.0, p = 0.003) and co-existence of coronary artery disease (OR = 8.68, 95% CI: 2.15-35.1, p = 0.002) as significant predictors for thoracic descending aorta dilatation. In patients with abdominal aorta dilatation, the multivariable analysis showed a predictive value of ascending aortic dilatation (OR = 14.8, 95% CI: 2.36-92.8, p = 0.004) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.027). In addition, cut-off values were established for age groups determining the risk of thoracic aorta dilatation over 49 years and abdominal aorta dilatation over 54 years. Conclusions: The results of our analysis showed predictive factors, including ascending aorta dilatation and co-existence of coronary artery disease, particularly over 49 years of age for thoracic, while ascending aorta dilatation and age, particularly over 54 years, for abdominal aorta dilatation. These features may be considered to increase clinical vigilance in patients with aortic diameter abnormalities.

Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

Neutrophil Extracellular Trap Formation in Advanced Heart Failure Patients-Preliminary Report.

In end-stage heart failure, which is characterized by persistent or progressive ventricular dysfunction despite optimal medical therapy, a left ventricular assist device (LVAD) can be beneficial. Congestive heart failure provokes inflammatory and prothrombotic activation. The aim of this study was to evaluate the serum concentration of citrullinated histone 3 (CH3) representing neutrophil extracellular trap (NET) formation in patients referred for LVAD implantation. There were 10 patients with a median age of 61 (57-65) years enrolled in a prospective single-center analysis who underwent LVAD implantation. The CH3 plasma concentration was measured preoperatively and on the 1st and 7th postoperative days, followed by control measurements on the median (Q1-3) 88th (49-143) day. The preoperative CH3 concentration strongly correlated with brain natriuretic peptide (r = 0.879, p < 0.001). Significant differences in CH3 serum concentration were observed between pre- and postoperative measurements, including an increase on the first postoperative day (p < 0.001), as well as a decrease on the seventh day (p = 0.016) and in follow-up (p < 0.001). CH3 concentration, as a marker of NET formation, decreases after LVAD implantation.

Long-Term Nitrogen Dioxide Exposure as a Possible 5-Year Mortality Risk Factor in Diabetic Patients Treated Using Off-Pump Surgical Revascularization-A Retrospective Analysis.

Background: There is mounting evidence that diabetic-related cardiac metabolism abnormalities with oxidative stress and inflammatory mechanism activation align with the functional impairments that result in atherosclerotic lesion formation. Among the possible non-traditional coronary lesion risk factors, environmental exposure may be significant, especially in diabetic patients. Methods: A total of 140 diabetic patients (115 (82%) males and 25 (18%) females) with a mean age of 65 (60-71) underwent surgical revascularization due to multivessel coronary disease. The possible all-cause mortality risk factors, including demographical and clinical factors followed by chronic air pollution exposure, were identified. Results: All patients were operated on using the off-pump technique and followed for 5.6 (5-6.1) years. The multivariable model for 5-year mortality prediction presented the nitrogen dioxide chronic exposure (HR: 3.99, 95% CI: 1.16-13.71, p = 0.028) and completeness of revascularization (HR: 0.19, 95% CI: 0.04-0.86, p = 0.031) as significant all-cause mortality risk factors. Conclusions: Ambient air pollutants such as an excessive chronic nitrogen dioxide concentration (>15 µg/m3) may increase 5-year all-cause mortality in diabetic patients following surgical revascularization.

Long-Term Survival after Coronary Artery Surgical Revascularization-Does Ambient Temperature Matter?

Background and Objectives: The progression of global warming results in an increased exposure to extreme heat, leading to exaggeration of preexisting diseases and premature deaths. The aim of the study was to present possible risk factors for all-cause long-term mortality in patients who underwent surgical revascularization, including an assessment of the influence of ambient temperature exposure. Materials and Methods: Retrospective analysis included 153 (123 (80%) males and 30 (20%) females) patients who underwent off-pump revascularization and were followed for a median time of 2533 (1035-3250) days. The demographical, clinical data and ambient temperature exposure were taken into analysis for prediction of all-cause mortality. Individual exposure was calculated based on the place of habitation. Results: In the multivariate logistic regression model with backward stepwise elimination method, risk factors such as dyslipidaemia (p = 0.001), kidney disease (p = 0.005), age (p = 0.006), and body mass index (p = 0.007) were found to be significant for late mortality prediction. In addition to traditional factors, environmental characteristics, including tropical nights (p = 0.043), were revealed to be significant. Conclusions: High night-time ambient temperatures known as tropical nights may be regarded as additional long-term mortality risk factor after surgical revascularization.

Relation between Systemic Inflammatory Index (SII) and Hair Trace Elements, Metals and Metalloids Concentration in Epicardial Coronary Artery Disease-Preliminary Report.

Background: Coronary artery atherosclerosis development and progression are related to generic, clinical, and lifestyle factors combined with inflammatory activation. The relationship between trace element concentration and morbidity is under investigation to gain a clearer understanding of underlying pathological processes. Methods: Thirty-five consecutive patients (22 males and 13 females) with a median [interquartile range (IQR)] age of 67 (61-73) years presenting with anginal symptoms were included in the single center prospective analysis in 2022 and divided into a epicardial coronary artery disease (CAD) and non-CAD group. Scalp hair chemical analysis and inflammatory markers from a peripheral blood count were analyzed. Results: The correlation analysis of elements and inflammatory indexes showed statistical significance between median hair lithium (Li) concentration and the systemic inflammatory index (SII) (r = -0.476, p = 0.046), antimony (Sb) (r = -0.521, p = 0.028) followed by chromium (Cr) (r = -0.478, p = 0.045) and iron (Fe) (r = -0.604, p = 0.008) in the CAD group. Similar correlations were not found in non-CAD group. Conclusions: The correlation between scalp hair lithium (Li), antimony (Sb), chromium (Cr) and iron (Fe) concentration and the systemic inflammatory index (SII) were revealed only in patients with coronary artery disease. Our analysis identified a strong correlation between inflammatory activation and iron concentration.

Coronary Artery Bypass Surgery: Comparing the Long-Term Impact of Total Arterial Grafting With Multiarterial Plus Saphenous Vein Grafting.

INTRODUCTION: This study aimed to compare the long-term outcomes in a propensity matched population receiving total arterial grafting (TAG) and multiple arterial grafts (MAG) in addition to saphenous vein graft (SVG) following multivessel coronary artery bypass grafting requiring at least three distal anastomoses. METHODS: In this retrospective study, 655 patients from two centers met the inclusion criteria and were divided into two groups: TAG group (n = 231) and MAG + SVG group (n = 424). Propensity score matching was performed resulting in 231 pairs. RESULTS: No significant differences were observed between both groups in terms of early outcomes. Survival probabilities at 5, 10, and 15 y were 89.1% versus 94.2%, 76.2% versus 76.1%, and 66.7% versus 69.8% in the TAG and MAG + SVG groups, respectively (hazard ratio stratified on matched pairs: 0.90; 95% confidence interval [0.45-1.77]; P = 0.754). Freedom from major adverse cardiac and cerebral events (MACCE) in the matched cohort did not show any significant difference between both groups. Probabilities at 5, 10, and 15 y were 82.7% versus 85.6%, 62.2% versus 75.3%, and 48.8% versus 59.5% in the TAG and MAG + SVG groups, respectively (hazard ratio stratified on matched pairs: 1.12; 95% confidence interval [0.65-1.92]; P = 0.679). Subgroup analyses of the matched cohort showed no significant difference between TAR with three arterial conduits compared to TAR with two arterial conduits with sequential grafting and MAG + SVG in terms of long-term survival and freedom from MACCE. CONCLUSIONS: Multiple arterial revascularizations in addition to SVG may yield comparable long-term outcomes in terms of survival and freedom from MACCE compared to total arterial revascularization.

The Significance of Simple Inflammatory Markers in Off Pump Surgery-Review.

The inflammatory background of coronary artery disease is gaining more attention in recent times. Off pump surgery is minimally invasive type of surgical revascularization with relatively low number of applications in cardiac surgery centers worldwide that allows for perioperative inflammatory reactions minimalization. The simple inflammatory markers (neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelets to lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), aggregate index of systemic inflammation (AISI)) possess a clinically significant impact on patients' prognosis and may help to improve patients' long-term results. The review presents the current knowledge regarding their utility in clinical practice. Assessment of inflammatory indices obtained from whole blood count analysis allows to indicate those patients who need scrupulous follow-up due to predicted worse long-term survival. Perioperative measurement and analysis of simple whole blood counts is inexpensive and easily available and may improve the results of surgical revascularization by better identification of patients at higher risk of worse outcomes.

Neutrophil Count as Atrioventricular Block (AVB) Predictor following Pediatric Heart Surgery.

Neutrophils play a significant role in immune and inflammatory reactions. The preoperative inflammatory activation may have a detrimental effect on postoperative outcomes. The aim of the study was to investigate the relation between preoperative hematological indices on postoperative complications' risk in pediatric cardiac congenital surgery. The retrospective single center analysis included 93 pediatric patients (48 (65%) males and 45 (35%) females), mean age of 7 (3−30) months referred for cardiac surgery in cardiopulmonary bypass due to functional single ventricle disease (26 procedures), shunts lesions (40 procedures) and cyanotic disease (27 procedures). Among simple hematological indices, the receiver-operating-characteristic curve showed that a neutrophil count below 2.59 K/uL was found as an optimal cut-off point for predicting postoperative atrioventricular block following pediatric cardiac surgery (AUC = 0.845, p < 0.0001) yielding a sensitivity of 100% and a specificity of 65.62%. Preoperative values of neutrophil count below 2.59 K/uL in whole blood analysis can be regarded as a predictive factor (AUC = 0.845, p < 0.0001) for postoperative atrioventricular block in pediatric cardiac surgery.

Cardioprotective Effect of Low Level of LDL Cholesterol on Perioperative Myocardial Injury in Off-Pump Coronary Artery Bypass Grafting.

Background and Objectives: Coronary artery disease is still a major cause of death in developed countries. Low-density lipoprotein cholesterol (LDL-C) lowering with statin therapy is a key strategy in major acute coronary events' prevention. The aim of the study was to establish if there is a cardioprotective effect of pre-operative LDL lowering therapy on perioperative myocaridal injury in patients undergoing off-pump coronary artery bypass grafting (CABG). Moreover, the impact of pre-operative LDL level on long term outcome was analysed. Materials and Methods: The retrospective single center analysis included 662 consecutive patients (431 (65%) males and 231 (35%) female, mean age of 65 ± 8) referred for cardiac surgery due to stable chronic coronary syndrome between 2012-2018. The follow up was 9 years. Results: A statistically significant difference was found in postoperative serum Troponin-I for LDL thresholds of 1.8 mmol/L (p = 0.009), 2.6 mmol/L (p = 0.03) and 3.0 mmol/L (p = 0.001). The results indicate that cardioprotective role of LDL is achieved within LDL concentration rate below 1.8 mmol/L (<70 mg/dL). Five patients died perioperatively, whereas 1-year and 9-year overall mortality rates were 4% (n = 28) and 18.6% (n = 123), respectively. Comparing the survival group with diseased, Mann-Whitney U test showed a statistically significant difference in HDL-C (p = 0.007), Troponin (p = 0.009), Castelli index (p = 0.001) and atherogenic index (p = 0.004). Preoperative levels of total cholesterol, LDL-C and HDL-C did not significantly differ between survivors and diseased. The 9-year mortality risk did not differ significantly between subgroups divided according to LDL-C thresholds of 1.4 mmol/L (55 mg/dL), 1.8 mmol/L (70 mg/dL), 2.6 mmol/L (100 mg/dL) and 3.0 mmol/L (116 mg/dL). Conclusions: Preoperative low level of LDL-C cholesterol (below 1.83 mmol/L, 70 mg/dL) has a cardioprotective effect on perioperative myocardial injury in off-pump coronary artery bypass grafting.

Neutrophile-to-Lymphocyte Ratio as a Predictor of Mortality and Response to Treatment in Invasive Aspergillosis among Heart Transplant Recipients-Exploratory Study.

Background and objective: Aspergillus pulmonary infections are potentially life-threatening complications that can occur after heart transplantation. The aim of the study was to find an easily available mortality predictor during Aspergillosis infection therapy following heart transplantation. Materials and methods: This study involved 15 heart recipients with the mean age of 55 ± 6 years who were diagnosed with invasive aspergillosis (IA) in a mean time of 80 ± 53 (19-209) days after orthotropic heart transplantation. Results: Out of fifteen patients diagnosed with IA, five died. The mean time from diagnosis to death in the deceased group was 28 ± 18 days. They were diagnosed with IA in a mean time of 80 ± 53 (19-209) days after orthotropic heart transplantation. During the initial seven days of therapy, the neutrophil to lymphocyte ratio (NLR) significantly differed between the two groups on day three and day seven, with median values of 10.8 [4.3-17.0] vs. 20.2 [17.4-116.8] (p = 0.0373) and 5.2 [3.2-8.1] vs. 32.2 [13.5-49.9] (p = 0.0101) in the survivor and the deceased group, respectively. The NLR was a significant predictor of death both on day three (cut-off point 17.2) and day seven (cut-off point 12.08) of therapy. Conclusions: Findings in our study indicate that NLR may be of predictive value in the estimation of mortality risk or response to treatment among patients with invasive aspergillosis following heart transplantation.

Monocyte-to-Lymphocyte Ratio as a Predictor of Worse Long-Term Survival after Off-Pump Surgical Revascularization-Initial Report.

Background and objective: Coronary artery disease is one of the leading causes of deaths nowadays and the trends in diagnosis and revascularization are still in plateau despite well-known factors. Simple whole blood count parameters may be used to measure inflammatory reactions that are involved in processes of atherosclerosis progression. The aim of our study was to analyse the association between simply available hematologic indices and long-term mortality following off-pump coronary artery bypass grafting (OPCAB). Material and Methods: The study group comprised 129 consecutive patients (16 females and 113 males, mean age 66 ± 6 years) who underwent surgical revascularization with off-pump technique between January 2014 and September 2019. The mean follow-up was 4.7 +/-1.9 years. A receiver operating characteristics curve was applied to estimate demographical and perioperative parameters including MLR for mortality. Results: Cox regression analysis revealed chronic pulmonary obstructive disease (HR = 2.86, 95%CI 1.05-7.78), MLR (HR = 3.81, 95%CI 1.45-10.06) and right coronary artery blood flow (HR = 1.06, 95%CI 1.00-1.10) as significant factors predicting increased mortality risk. In the presented model, the MLR > 1.44 on 1st postoperative day was a significant predictor of late mortality after the OPCAB procedure (HR = 3.82, 95%CI 1.45-10.06). Conclusions: Pronounced inflammatory reaction after off-pump surgery measured by MLR > 1.44 can be regarded as a worse long-term prognostic factor.

Pre-procedural abnormal function of von Willebrand Factor is predictive of bleeding after surgical but not transcatheter aortic valve replacement.

Both transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have been proven to effectively correct von Willebrand Factor (vWF) pathologies, however there is limited data simultaneously comparing outcomes of both approaches. We prospectively enrolled patients with severe aortic stenosis referred for TAVI (n = 52) or SAVR (n = 48). In each case, vWF antigen (vWF:Ag), vWF activity (vWF:Ac) and activity-to-antigen (vWF:Ac/Ag) ratio were assessed at baseline, 24 h and 72 h after procedure. VWF abnormalities were defined as reduced vWF:Ac/Ag ratio (< 0.8). Bleeding events in both arms were classified according to Valve Academic Research Consortium (VARC-2) definitions. Overall, there was no difference between patients referred for TAVI and SAVR in vWF:Ac (1.62 ± 0.52 vs 1.71 ± 0.64; p = 0.593), vWF:Ag (1.99 ± 0.81 vs 2.04 ± 0.81; p = 0.942) or vWF:Ac/Ag ratio (0.84 ± 0.16 vs 0.85 ± 0.12; p = 0.950). Pathological vWF:Ac/Ag ratio was found in 20 (38%) TAVI and 15 (31%) SAVR patients (p = 0.407). Normalization of vWF:Ac/Ag ratio at day 3 after procedure was achieved in 19 (95%) TAVI and 13 (87%) SAVR patients (p = 0.439). Similar prevalence of major or life-threatening bleedings (MLTB) after TAVI and SAVR in entire groups was observed (19% vs. 23%, p = 0.652). VWF abnormalities were associated with higher incidence of MLTB in SAVR (53% vs 9%, p < 0.001), but not TAVI (15% vs. 22%, p = 0.132). Accordingly, in receiver-operating characteristic curve analysis vWF:Ac/Ag ratio < 0.8 showed significant sensitivity and specificity for predicting MLTB in SAVR group (AUC 0.735, 95% CI 0.538-0.931, p = 0.019). We proved that abnormal function of vWF is corrected successfully after both TAVI and SAVR, but vWF abnormalities are predictive of MLTB only in surgical patients.

Concomitant coronary artery disease and its management in patients referred to transcatheter aortic valve implantation: Insights from the POL-TAVI Registry.

BACKGROUND: Coronary artery disease (CAD) and degenerative aortic stenosis often coexist. However, the impact of CAD and its management on the prognosis after transcatheter aortic valve implantation (TAVI) remains uncertain. We sought to evaluate the impact of obstructive CAD, SYNTAX score (Ss), and percutaneous coronary intervention (PCI) prior to TAVI on short-term outcome. METHODS: Overall, 896 patients who underwent TAVI after heart team decision was included. Pre-procedural angiograms were analysed to calculate baseline Ss (bSs) and residual Ss (rSs). Baseline, procedural and follow-up data up to 30 days was acquired from the national POL-TAVI registry. RESULTS: Patients with obstructive CAD at baseline (n = 462, 52%) had higher mortality as compared with the remaining (8.7 vs. 5.1%, log-rank P = 0.039). Also, after correction for confounding factors obstructive CAD was identified as independent predictor of mortality (hazard ratio [HR] 1.74, 95% confidence intervals [CIs] 1.03-2.94, P = 0.037). In obstructive CAD, neither bSs (AUC 0.47, CI 0.38-0.56, P = 0.47) nor rSs (AUC 0.47, CI 0.30-0.64, P = 0.72 for those undergoing PCI and AUC 0.48, CI 0.37-0.59, P = 0.75 for the remaining) was predictive of mortality. When revascularization status was considered, patients with PCI prior to TAVI had similar outcome as those without obstructive CAD at baseline (7.7 vs. 5.1%, log-rank P = 0.23) with no negative impact on mortality (HR 1.13, CI 0.62-2.09, P = 0.69). CONCLUSIONS: In conclusion, obstructive CAD at baseline evaluation for TAVI has independent negative impact on short-term prognosis. However, neither baseline nor residual Ss values have prognostic ability in patients undergoing TAVI. Revascularization prior to TAVI seems to improve survival to levels comparable with patients without obstructive CAD at baseline.

Neopterin as a Biomarker in Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Upregulation of the immune system is regarded to play an important role in the etiopathobiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, neopterin (NP) has never been investigated in patients with PAH and CTEPH. OBJECTIVES: The aim of the study was to evaluate the concentration of NP in blood in order to examine its impact on outcome and relationship with disease severity in that population. METHODS: Serum concentration of NP was analysed prospectively in 50 patients (36 with PAH and 14 with CTEPH vs. 31 healthy controls) and assessed in relation to clinical parameters and outcome. RESULTS: NP concentration in the PAH and CTEPH groups combined was significantly higher than in the control group (8.68, 6.39-15.03 vs. 5.14, 4.16-5.98 nmol/L, p < 0.0000001). During 9 months of follow-up, clinical deterioration occurred in 18 patients (including 8 deaths), and NP concentration in this group was higher when compared to stable patients (15.6, 8.52-25.13 vs. 7.87, 6.18-9.89, p = 0.002). The cutoff value of NP derived from ROC curve analysis was 15.3 nmol/L (p = 0.002, AUC 0.77, p = 0.0004, HR = 4.35, 95% CI 1.43-13.18, log-rank test). On Cox regression analysis, NP predicted clinical deterioration (p = 0.009, 95% CI 1.01-1.06). NP correlated positively with NT-proBNP (p < 0.001), red blood cell distribution width (p < 0.001), and right atrium area (p = 0.002) and inversely with 6-min walking test (p = 0.002) and peak oxygen consumption (p = 0.001). CONCLUSIONS: NP concentration is increased in patients with PAH and inoperable CTEPH. Elevated NP concentration is associated with adverse clinical outcomes and correlates with clinical parameters.

Red Blood Cells Distribution Width as a Potential Prognostic Biomarker in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Red blood cells distribution width (RDW) predicts survival in cardiovascular diseases. Little is known about the variability of RDW level over time among patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). To our knowledge, RDW has never been analysed as a marker of response to specific treatment. MATERIALS AND METHODS: We retrospectively analysed 77 patients for: i) RDW measured during the last hospitalisation before death or during the last follow-up (RDWlast); ii) mean RDW from all hospitalisations during the entire follow-up of the patient (RDWmean); iii) maximum RDW of all hospitalisations of each patient (RDWmax). In order to assess response to specific treatment and association with prognosis, we compared RDW levels (obtained from 56 patients) before and 3 to 6 months after introduction or intensification of treatment in both the alive and deceased group. RESULTS: Twenty-eight of 77 patients died, whereas in specific drugs treatment response analysis, 22 of 56 patients died during follow-up. The cut-off values derived from the ROC analysis and assessed using the log-rank test were significant for RDWlast (p<0.0001), RDWmean (p<0.001) and RDWmax (p=0.02). A decrease in RDW levels after introduction or intensification of specific treatment was significant (p=0.015) in survivors, whereas there was no significance (p=0.29) in decrease in RDW levels in non-survivors after change of therapy. CONCLUSIONS: Red blood cells distribution width might be a potential prognostic biomarker in patients with PAH and inoperable CTEPH. The decrease in RDW level after introduction or escalation of PAH-targeted and CTEPH-targeted drugs is associated with a good treatment response and better prognosis.

The Management of Supraventricular Tachyarrhythmias in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Atrial remodelling in pulmonary arterial hypertension (PAH) may lead to higher incidence of supraventricular arrhythmias (SVA). The purpose of this study was to evaluate the efficiency and safety of various methods for treatment of SVA in this group. METHODS: This was a single centre study. Forty-eight patients (33 women and 15 men) aged 19-77 years (median 49 years) were enrolled. There were 30 patients with idiopathic PAH, 10 had PAH associated with connective tissue disease, and eight with congenital heart disease. A retrospective analysis was performed to estimate the prevalence and type of supraventricular arrhythmias, as well as efficiency and safety of treatment methods. Mean follow-up period was 28.8±17.7 months. RESULTS: Supraventricular arrhythmias occurred in 17 patients (35%) and appeared to be atrial fibrillation, flutter or tachycardia. Supraventricular arrhythmias coexisted with elevated mean right atrial pressure in 75%. Four patients had more than one type of SVA. A flutter-like macro-reentrant form of atrial tachycardia dependent on cavo-tricuspid isthmus was found in four cases. The treatment of SVA included typical methods: antiarrhythmic drugs, direct current cardioversion (DCC), and radiofrequency (RF) ablation. All of the therapeutic methods were effective in managing acute arrhythmia. Three patients required re-ablation. Overall mortality: 14 patients (29%) in the whole study group, including six in SVA group (35%) and eight without SVA (26%). CONCLUSIONS: In patients with PAH DCC, pharmacological cardioversion and RF ablation can be applied safely and effectively. Flutter-like macro-reentrant atrial tachycardia dependent on cavo-tricuspid isthmus is observed in this group. It is more challenging, but possible, to successfully treat this arrhythmia with RF ablation.

Cardiovascular safety of antihistamines.

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the 'rapid' I Kr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk.

Serum Uric Acid as an Indicator of Right Ventricular Dysfunction in LVAD Patients: A Preliminary Study.

(1) Background: Left ventricular assist devices (LVADs) represent mechanical support in end-stage congestive heart failure and are characterized by satisfactory long-term results. Uric acid (UA) represents one of the early heart failure markers whose usefulness was postulated in clinical practice. (2) Methods: Twenty-nine male patients with a median age of 58 (51-62) years were referred for LVAD implantation due to end-stage congestive heart failure in the mean (SD) New York Heart Association (NYHA) status class 3.3 (0.6). Preoperative and postoperative right ventricular (RV) characteristics were compared with serum uric acid concentration within 12 (8-15) months following the implantation. (3) Results: Significant correlations between postoperative uric acid concentration and right ventricular dimension (r = 0.604, p = 0.005), tricuspid annulus plane systolic excursion (TAPSE) (r = -0.496, p = 0.022), left ventricular ejection fraction (r = -0.463, p = 0.046), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) (r = 0.505, p = 0.041) were noted. (4) Conclusions: The analysis shows the association between the postoperative RV diameter and TAPSE results in LVAD patients and uric acid concentration. Serum uric acid can be regarded as a possible right ventricular dysfunction marker in LVAD patients.