Adverse Effects of Meditation: Autonomic Nervous System Activation and Individual Nauseous Responses During Samadhi Meditation in the Czech Republic.

Buddhist meditation practices, including Samadhi meditation, which forms the basis for mindfulness practice, are broadly promoted as pathways to wellbeing, but evidence of their adverse effects is emerging. In a single-group observational study with assessments of autonomic system before, during, and after Samadhi meditation, we explore the relationship between post-meditation nausea symptoms and the degree of change in autonomic system activity during meditation as compared to before and after in 57 university students (42 women; mean age = 22.6) without any previous experience in meditation or yoga practices. We hypothesize that nauseous feelings in meditation are connected to a rapid increase of activity in the sympathetic nervous system, as indicated by decreased heart-rate variability (HRV). We additionally explore links between meditation-induced nausea and two markers of parasympathetic activity: increased HRV and vasovagal syncope. Engaging in meditation and increased nausea during meditation were both associated with increased markers of HRV parasympathetic activity, but 12 individuals with markedly higher nausea demonstrated increased HRV markers of sympathetic activity during meditation. Vasovagal syncope was observed but found to be unrelated to nausea levels. Drivers of adverse effects of meditation in some individuals require further investigation.

Computed tomography is better than echocardiography in predicting balloon-expandable transcutaneous implantation valve size in a real-world clinical practice single-center study.

AIMS: Transcatheter aortic valve replacement (TAVR) has become the standard of care for selected patients with severe aortic stenosis. Multidetector computed tomography (MDCT) and transoesophageal 2D/3D (two-dimensional/three-dimensional) echocardiography (ECHO) are used for aortic annulus (AA) sizing. The aim of this study was to compare the accuracy of AA sizing by ECHO versus MDCT for Edwards Sapien balloon expandable valve in a single center. METHODS AND RESULTS: Data from 145 consecutive patients with TAVR (Sapien XT or Sapien S3) were analyzed retrospectively. A total of 139 (96%) patients had favorable outcomes after TAVR (at most mild aortic regurgitation and only one valve implanted). The 3D ECHO AA area and area-derived diameter were smaller than the corresponding MDCT parameters (464 ± 99 vs. 479 ± 88 mm2 , p < .001, and 24.2 ± 2.7 vs. 25.0 ± 5.5 mm, p = .002, respectively). The 2D ECHO annulus measurement was smaller than both the MDCT and 3D ECHO area-derived diameters (22.6 ± 2.9 vs. 25.0 ± 5.5 mm, p = .013, and 22.6 ± 2.9 vs. 24.2 ± 2.7 mm, p < .001, respectively) but larger than the minor axis diameter of the AA derived from MDCT and 3D ECHO by multiplanar reconstruction (p < .001). The 3D ECHO circumference-derived diameter was also smaller than the MDCT circumference-derived diameter (24.3 ± 2.5 vs. 25.0 ± 2.3, p = .007). The sphericity index by 3D ECHO was smaller than that by MDCT (1.2 ± .1 vs. 1.3 ± .1, p < .001). In up to 1/3 of the patients, 3D ECHO measurements would have predicted different (generally smaller) valve size than was the valve size implanted with favorable result. The concordance of the implanted valve size with the recommended size based on preprocedural MDCT and 3D ECHO AA area was 79.4% versus 61% (p = .001), and for the area-derived diameter, the concordance was 80.1% versus 61.7% (p = .001). 2D ECHO diameter concordance was similar to MDCT (78.7%). CONCLUSIONS: 3D ECHO AA measurements are smaller than MDCT measurements. If 3D ECHO-based parameters alone are used to size the Edwards Sapien balloon expandable valve, then the selected valve size would have been smaller than the valve size implanted with favorable result in 1/3 of the patients. MDCT preprocedural TAVR assessment should be the preferred method over 3D ECHO in routine clinical practice to determine Edwards Sapien valve size.

The decline in stroke hospitalization due to COVID-19 is unrelated to COVID-19 intensity.

BACKGROUND AND PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic many countries reported a decline in stroke volumes. The aim of this study was to analyze if the decline was related to the intensity of the COVID-19 pandemic. METHODS: The first pandemic year (1 March 2020 to 28 February 2021) overall and during the three COVID-19 waves were compared with the preceding year. Volumes of acute ischaemic stroke (AIS), subarachnoid hemorrhage, intracerebral hemorrhage and recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) were obtained from the National Register of Reimbursed Health Services. Door-to-needle time, onset-to-door time and National Institutes of Health Stroke Scale at admission were obtained from the Registry of Stroke Care Quality. RESULTS: During the pandemic year compared to the preceding year there were 26,453 versus 28,771 stroke admissions, representing an 8.8% decline (p < 0.001). The declines (-10%, -11%, -19%) appeared in COVID-19 waves (spring 2020, autumn 2020, winter 2021) except for an increase (2%) during summer 2020. Admissions for AIS declined by 10.2% (p < 0.001), whilst hemorrhagic stroke volumes were minimally decreased. The absolute volumes of IVT and MT decreased by 9.4% (p < 0.001) and 5.7% (p = 0.16), respectively. However, the proportions of ischaemic stroke patients receiving IVT (18% vs. 18%; p = 0.72) and MT (6% vs. 6%; p = 0.28) remained unchanged. CONCLUSIONS: There was a decline in stroke admissions, but such decline was not related to COVID-19 incidence. The frequency of use of recanalization procedures (IVT, MT) and times (onset-to-door time, door-to-needle time) in AIS were preserved in the Czech Republic during the first year of the pandemic.

Survival and lung function decline in patients with definite, probable and possible idiopathic pulmonary fibrosis treated with pirfenidone.

BACKGROUND: There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a lower degree of diagnostic certainty. We report on outcomes of treatment with pirfenidone in IPF patients diagnosed with various degrees of certainty. METHODS AND FINDINGS: We followed patients in the multi-national European MultiPartner IPF Registry (EMPIRE) first seen between 2015 and 2018. Patients were assessed with HRCT, histopathology and received a multi-disciplinary team (MDT) IPF diagnosis. Endpoints of interest were overall survival (OS), progression-free survival (PFS) and lung function decline. RESULTS: A total of 1626 patients were analysed, treated with either pirfenidone (N = 808) or receiving no antifibrotic treatment (N = 818). When patients treated with pirfenidone were compared to patients not receiving antifibrotic treatment, OS (one-, two- and three-year probability of survival 0.871 vs 0.798; 0.728 vs 0.632; 0.579 vs 0.556, P = 0.002), and PFS (one-, two- and three-year probability of survival 0.597 vs 0.536; 0.309 vs 0.281; 0.158 vs 0.148, P = 0.043) was higher, and FVC decline smaller (-0.073 l/yr vs -0.169 l/yr, P = 0.017). The benefit of pirfenidone on OS and PFS was also seen in patients with probable or possible IPF. CONCLUSIONS: This EMPIRE analysis confirms the favourable outcomes observed for pirfenidone treatment in patients with definitive IPF and indicates benefits also for patients with probable or possible IPF.

Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry. METHODS: For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment. RESULTS: A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths. CONCLUSIONS: The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

Oncological outcomes of surgery for isolated retroperitoneal recurrence in renal cancer patients after radical nephrectomy.

AIMS: Isolated retroperitoneal recurrence (IRR) in renal cancer patients after radical nephrectomy (RN) is a rare event and poses a therapeutic dilemma. We evaluated oncologic outcomes in surgically treated patients with IRR and established prognostic factors associated with survival. The benefit of metastasis-directed therapy (MDT) in those with clinical progression after extirpation of IRR was assessed. METHODS: This was a retrospective single-institutional study in which 60 renal cancer patients after previous RN underwent surgery for suspicion of IRR within the period of 2004-2019; in 55 of them, RCC recurrence was histologically confirmed. No patient had distant metastatic disease at the time of IRR diagnosis. In cases of clinical progression after IRR surgery, MDT (metastasectomy, stereotactic radiotherapy) was selectively used. Kaplan-Meier curves were used to estimate survival outcomes. Univariable and multivariable Cox proportional hazards regression analyses were used to evaluate associations between clinicopathological parameters and cancer-specific survival. RESULTS: Median age at IRR diagnosis was 64 years (range 23-81). IRR was diagnosed at a median of 42 months (IQR 19-99) after RN. Surgical complications of grade 3-5 after IRR extirpation were rare (7%). Median follow-up time was 50 months (IQR 19-80). Five-year recurrence-free survival and cancer-specific survival rates were 32% and 66%, respectively. Radiographic progression was observed in 34 (62%) patients at a median of 11 months after IRR surgery, out of which 22 patients (40%) underwent MDT. When compared with 12 patients without MDT, the MDT patients had a prolonged median time to systemic treatment of 58 (vs. 16 months), and median cancer-specific survival of 88 (vs. 46 months). Upon multivariable analysis, the interval from nephrectomy ≤12 months (HR 7.77), tumour grade 3-4 (HR 13.24) and female sex (HR 7.42) were determined to be independent prognostic factors of cancer-related mortality. CONCLUSION: Aggressive surgical therapy of IRR is feasible with relatively low morbidity. More than half of the patients experience long-term survival. The interval from nephrectomy to IRR less than 12 months, tumour grade 3-4 and female sex were negative prognostic predictors. In the case of progression, metastasis-directed therapy may prolong the interval to initiation of systemic treatment.

Treat COVID-19, but Not Only COVID-19: Stroke Matters as Well.

INTRODUCTION: During the COVID-19 pandemic, studies reported less number of hospitalizations for acute stroke and reduction in the use of recanalization treatments. This study analyzes nationwide data on stroke admissions and management in the Czech Republic during the first wave of the COVID-19 pandemic. METHODS: We compared the early COVID-19 pandemic (March-May 2020) with the pre-pandemic period (January-February 2020 and March-May 2019): (a) the National Register of Reimbursed Health Services provided volume of all admissions for subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and ischemic stroke (IS), and volume of recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]); (b) Registry of Stroke Care Quality provided door-to-needle time (DNT), onset-to-door time (ODT), and stroke severity at admission (National Institutes of Health Stroke Scale, NIHSS) for IS. RESULTS: During the pandemic (March-May 2020), the peak number of COVID-19 patients treated in Czech hospitals was 39 per million. In March-May 2020 versus March-May 2019, hospital admissions decreased as follows: stroke overall by 14% (p < 0.001), IS by 14% (p < 0.001), SAH by 15% (p = 0.07), and ICH by 7% (p = 0.17). The mean age was 74 years versus 74 years (p = 0.33), and 52% versus 51% were men (p = 0.34). The volumes of IVT and MT decreased by 14% (p = 0.001) and 19% (p = 0.01), respectively. The proportions of all IS patients receiving IVT or MT remained unchanged, with, respectively, 17% versus 17% receiving IVT (p = 0.86) and 5% versus 5% receiving MT (p = 0.48). DNT and ODT were 24 versus 25 min (p = 0.58) and 168 versus 156 min (p = 0.23), respectively. NIHSS at admission did not differ (6 vs. 6; p = 0.54). CONCLUSION: Even with a low burden of COVID-19 during the first wave and no change in organization and logistics of stroke services, stroke admissions and volume of recanalization treatments decreased. Public health communication campaigns should encourage people to seek emergency medical care for stroke symptoms during the COVID-19 pandemic.

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study.

BACKGROUND: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. METHODS: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients (n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals (n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. RESULTS: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56-40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68-43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13-0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival. CONCLUSION: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.

Differences in Baseline Characteristics and Access to Treatment of Newly Diagnosed Patients With IPF in the EMPIRE Countries.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with poor prognosis. The diagnosis and treatment possibilities are dependent on the health systems of countries. Hence, comparison among countries is difficult due to data heterogeneity. Our aim was to analyse patients with IPF in Central and Eastern Europe using the uniform data from the European Multipartner IPF registry (EMPIRE), which at the time of analysis involved 10 countries. Newly diagnosed IPF patients (N = 2,492, between March 6, 2012 and May 12, 2020) from Czech Republic (N = 971, 39.0%), Turkey (N = 505, 20.3%), Poland (N = 285, 11.4%), Hungary (N = 216, 8.7%), Slovakia (N = 149, 6.0%), Israel (N = 120, 4.8%), Serbia (N = 95, 3.8%), Croatia (N = 87, 3.5%), Austria (N = 55, 2.2%), and Bulgaria (N = 9, 0.4%) were included, and Macedonia, while a member of the registry, was excluded from this analysis due to low number of cases (N = 5) at this timepoint. Baseline characteristics, smoking habit, comorbidities, lung function values, CO diffusion capacity, high-resolution CT (HRCT) pattern, and treatment data were analysed. Patients were significantly older in Austria than in the Czech Republic, Turkey, Hungary, Slovakia, Israel, and Serbia. Ever smokers were most common in Croatia (84.1%) and least frequent in Serbia (39.2%) and Slovakia (42.6%). The baseline forced vital capacity (FVC) was >80% in 44.6% of the patients, between 50 and 80% in 49.3%, and <50% in 6.1%. Most IPF patients with FVC >80% were registered in Poland (63%), while the least in Israel (25%). A typical usual interstitial pneumonia (UIP) pattern was present in 67.6% of all patients, ranging from 43.5% (Austria) to 77.2% (Poland). The majority of patients received antifibrotic therapy (64.5%); 37.4% used pirfenidone (range 7.4-39.8% between countries); and 34.9% nintedanib (range 12.6-56.0% between countries) treatment. In 6.8% of the cases, a therapy switch was initiated between the 2 antifibrotic agents. Significant differences in IPF patient characteristics and access to antifibrotic therapies exist in EMPIRE countries, which needs further investigation and strategies to improve and harmonize patient care and therapy availability in this region.

Anticoagulant Use and Bleeding Risk in Central European Patients with Idiopathic Pulmonary Fibrosis (IPF) Treated with Antifibrotic Therapy: Real-World Data from EMPIRE.

INTRODUCTION: Nintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF). OBJECTIVE: Our objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy. METHODS: The European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized. RESULTS: Group A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively). CONCLUSION: Real-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).

Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury.

BACKGROUND/AIMS: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients. METHODS: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model. RESULTS: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI. CONCLUSION: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

Heart failure oral therapies at discharge are associated with better outcome in acute heart failure: a propensity-score matched study.

AIMS: Heart failure oral therapies (HFOTs), including beta-blockers (BB), renin-angiotensin system inhibitors (RASi) and mineralocorticoid receptor antagonists, administered before hospital discharge after acute heart failure (AHF) might improve outcome. However, concerns have been raised because early administration of HFOTs may worsen patient's condition. We hypothesized that HFOTs at hospital discharge might be associated with better post-discharge survival. METHODS AND RESULTS: The study population was composed of 19 980 AHF patients from the GREAT registry. The primary and secondary outcomes were 90-day and 1-year all-cause mortality, respectively. Survival was estimated with univariate and covariate-adjusted Cox proportional hazards regression models for the whole population and after propensity-score matching. HFOTs at discharge were consistently associated with no excess mortality in the unadjusted and adjusted analyses of the whole and matched cohorts. In the matched cohort, BB and RASi at discharge were associated with lower 90-day mortality risks compared to the respective untreated groups [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.69; and HR 0.53, 95% CI 0.42-0.66, respectively]. The favourable associations of BB and RASi at discharge with 90-day mortality were present in many subgroups including patients with reduced or preserved left ventricular ejection fraction and persisted up to 1 year after discharge. The combination of RASi and BB was associated with an even lower risk of death than RASi or BB alone. CONCLUSIONS: Administration of HFOTs at hospital discharge is associated with better survival of AHF patients.

Patent Foramen Ovale and the Risk of Cerebral Infarcts in Acute Pulmonary Embolism-A Prospective Observational Study.

BACKGROUND: Pulmonary embolism (PE) is associated with a risk of consecutive paradoxical embolism with brain infarction through a patent foramen ovale (PFO). The aims of this study were to assess the rate of new ischemic brain lesions (IBLs) using magnetic resonance imaging (MRI) during a 12-month follow-up period with anticoagulation and to evaluate the potential relationship with the presence of PFO on transesophageal echocardiography (TEE). SUBJECTS AND METHODS: Seventy-eight patients with acute PE underwent baseline contrast TEE with brain MRI. After the 12-month follow-up, 58 underwent brain MRI. The rates of MRI documenting new IBLs were measured based on the presence of PFO. RESULTS: PFO was detected in 31 patients (39.7%). At baseline MRI, IBL was present in 39 of 78 patients (50%). The presence of IBL was not significantly higher in patients with PFO than in patients without PFO (20 [64.5% patients with PFO] versus 19 [40.4% without PFO] of 39 patients with baseline IBL, P = .063). At the follow-up MRI, in the group with new IBL (9 of 58 patients, 15.5%), the number of patients with PFO was significantly higher than that without PFO (7 [33.3%] versus 2 [5.4%], P = .008). PFO was identified as an independent predictor of new IBL (odds ratio 4.6 [1.6-47.4], P = .008). CONCLUSIONS: The presence of PFO was associated with new IBL in patients with PE. These patients are at a higher risk of ischemic stroke despite effective anticoagulation therapy.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial.

AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial. METHODS AND RESULTS: A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable (n = 1361) and relax-non-comparable (n = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future. CONCLUSIONS: Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial infarction.

The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.

Plasma Levels of Soluble CD146 Reflect the Severity of Pulmonary Congestion Better Than Brain Natriuretic Peptide in Acute Coronary Syndrome.

BACKGROUND: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. METHODS: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. RESULTS: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. CONCLUSIONS: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis.

Natriuretic peptides in addition to Zwolle score to enhance safe and early discharge after acute myocardial infarction: A prospective observational cohort study.

BACKGROUND: The Zwolle score is recommended to identify low-risk patients eligible for early hospital discharge after ST-elevation myocardial infarction (STEMI), but since only one third of STEMI has low Zwolle score, hospital discharge is frequently delayed. B-type natriuretic peptide (BNP) also provides prognostic information after STEMI. The aim of the study was to test the hypothesis that patients with high Zwolle score associated with low BNP share similar outcomes than those with low Zwolle score. METHODS AND RESULTS: The study population consisted of 1032 consecutive STEMI patients in whom BNP was measured 24h after chest pain onset. The area under the curve of Zwolle score and plasma BNP for 30-day mortality were 0.82 and 0.87, p=0.39. A BNP threshold of 200pg/ml had sensitivity of 100% and specificity of 34% for predicting 30-day mortality. Patients with high Zwolle score and BNP≤200pg/ml (n=183) had similar mortality and hospital stay to those with low Zwolle score (0% vs. 0.5% and 5 vs. 5days, both p=1.0). By contrast, patients with high Zwolle score and BNP>200pg/ml had the highest mortality (6.7%) and the longest hospital stay (6days), both p<0.01. CONCLUSION: STEMI patients with high Zwolle score but low BNP share similar outcomes with those with low Zwolle score and should be eligible for early discharge. Hence, using the rule of "low-Zwolle or low-BNP" might increase the number of STEMI patients that might be eligible for early discharge.

Natriuretic peptides, nitrite/nitrate and superoxide dismutase have additional value on top of the GRACE score in prediction of one-year mortality and rehospitalisation for heart failure in STEMI patients - Multiple biomarkers prospective cohort study.

BACKGROUND: Blood-based biomarkers have a prognostic value in patients with myocardial infarction. The aim of our prospective observational cohort study was to evaluate the prognostic value of biomarkers of different pathophysiological pathways for the occurrence of 1-year all-cause mortality and hospitalisation due to acute heart failure. METHODS AND RESULTS: In 593 patients with ST-segment elevation MI (STEMI) treated by primary PCI, biomarkers were evaluated at 24h after MI onset. A minimum of three-year follow-up was achieved in all patients. The combination of 1-year all-cause mortality and hospitalisation due to heart failure was the primary endpoint. A cohort for validation of our combined GRACE-natriuretic peptide (NP) score included 667 STEMI patients. The primary endpoint was reached in 9.3% of patients. Among 21 biomarkers, only B-type natriuretic peptide (BNP), NT-proBNP, superoxide dismutase and nitrite/nitrate, added to clinical GRACE score led to a significant increase in the area under the curve of C statistics, in comparison to GRACE alone (tested by Delong's test). Continuous net reclassification improvement and integrated discrimination index demonstrated an improved reclassification and discrimination of the GRACE model for SOD, BNP and NT-proBNP, and improved reclassification for nitrite/nitrate. Consistent results for this new combined prognostic model GRACE-NP were found also for a validation cohort. CONCLUSIONS: The levels of NP have an additional value to the prognostic properties of the GRACE score for the prediction of the combined endpoint of one-year mortality or hospitalisation for AHF. Nitrite/nitrate and SOD are strong prognostic factors, even on top of the GRACE score.

Factors underlying elevated troponin I levels following pacemaker primo-implantation.

BACKGROUND: Cardiac troponins are routinely used as markers of myocardial damage. Originally, they were only intended for use in diagnosing acute coronary syndromes; however, we now know that raised serum troponin levels are not always caused by ischemia. There are many other clinical conditions that cause damage to cardiomyocytes, leading to raised levels of troponin. However, the specificity of cardiac troponins towards the myocardium is absolute. Our work focuses on mechanical damage to the myocardium and on monitoring the factors that raise the levels of cardiospecific markers after primo-implantation of a pacemaker with an actively fixed electrode. AIMS: (i) To determine whether the use of a primo-implanted pacemaker with an electrode system with active fixation will raise troponin levels over baseline. (ii) To assess whether troponin I elevation is dependent on procedure complexity. METHODS: We enrolled 219 consecutive patients indicated for pacemaker primo-implantation; cardiospecific marker values (troponin I, CKMB, myoglobin) were determined before the implantation procedure and again at 6- and 18-h intervals after the procedure. We monitored duration of cardiac skiascopy, number of attempts to place the electrode (active penetration into the tissue) and intervention range (single-chamber versus dual-chamber pacing), and we assessed the clinical data. RESULTS: The average age of the enrolled patients was 78.2 ± 8.0 years (median age, 80 years); women constituted 45% of the group. We implanted 128 dual-chamber and 91 single-chamber devices with an average skiascopic time of 38.6 ± 22.0 s (median, 33.5 s). Troponin I serum levels increased from an initial 0.03 ± 0.07 µg/L (median, 0.01) to 0.18 ± 0.17 µg/L (median, 0.13) and 0.09 ± 0.18 µg/L (median, 0.04) at 6 and 18 h, respectively. The differences were statistically significant (P < 0.001 or P < 0.001). We confirmed a correlation between troponin increase and duration of skiascopy (P < 0.001). We also demonstrated a correlation between increased troponin I and number of attempts to place a pacemaker electrode (penetration into the tissue) at 6 h (P < 0.001) post-implantation. CONCLUSION: We detected slightly elevated troponin I levels in patients with primo-implanted pacemakers using electrodes with active fixation. We demonstrated a direct correlation between myocardial damage (number of electrode penetrations into the myocardium) and troponin I elevation, as well as between complexity (severity) of the implantation procedure (indicated by prolonged skiascopy) and raised troponin I. The described phenomenon demonstrates the loss of the diagnostic role of troponin I early after pacemaker primo-implantation in patients with concomitant chest pain.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUND: The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 µmol/l), D--diabetes mellitus) scoring system. METHODS: AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). RESULTS: Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001). CONCLUSION: The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.