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.

Atrial fibrillation in young ischemic stroke patients: an underestimated cause?

BACKGROUND: Undetected atrial fibrillation (AF) is often suspected as the possible cause in patients with cryptogenic ischemic stroke (IS), especially in elderly population. In young IS patients, the prevalence of AF, particularly paroxysmal form, remains still not enough established. Our aim was to assess the presence of AF in young patients using a long-term electrocardiography (ECG) Holter monitoring. METHODS: The study set consisted of acute IS patients ≤50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study (NCT01541163). In all patients, admission ECG, serum cardiac markers, transesophageal echocardiography, 24-h and 3-week ECG Holter monitoring were performed. RESULTS: Out of 634 enrolled patients in the HISTORY study, 98 were ≤50 years (56 males, mean age 39.7 ± 8.4). In total, AF was detected in 10.2% of patients and 70% of them had a paroxysmal form of AF. The elevated serum cardiac markers were present in 70% of patients with detected AF (p = 0.0001). CONCLUSION: AF was detected in 10.2% of young stroke patients and paroxysmal form of AF prevailed. Using of long-term ECG Holter monitoring improved the detection of AF. Patients with presence of AF had more frequently elevated serum specific cardiac markers.

High incidence of acute and subacute ischaemic foci on brain MRI in patients with a diagnosis of acute pulmonary embolism and confirmed patent foramen ovale.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially life-threatening diagnosis when a certain amount of thrombotic mass obstructs blood flow through the pulmonary circulation. The finding of acute and subacute ischaemic foci on magnetic resonance imaging (MRI) of the brain in a group of patients with this diagnosis in whom we demonstrate the presence of patent foramen ovale (PFO) by transoesophageal echocardiography (TEE) is surprisingly high. METHODS: A total of 129 patients with a diagnosis of pulmonary embolism (confirmed by computed tomography with contrast agent, CTA) who consented to further examination were examined by transthoracic echocardiography (TTE) and transoesophageal echocardiography (TEE) with contrast agent, underwent magnetic resonance imaging of the brain according to a specific protocol, and underwent a comprehensive baseline laboratory examination. RESULTS: In our group of 129 patients, we found the presence of PFO in 36.4% (n=47) of them. A total of 5.4% (n=7) patients had asymptomatic acute and subacute ischaemic changes on brain MRI; 6 of them had concomitant PFO. The statistically significant correlation between troponin levels and the presence of pathological findings on MRI and the trend of a similar correlation for NT-proBNP values is also very interesting finding. CONCLUSIONS: The association between the presence of PFO and the occurrence of symptomatic or asymptomatic findings on brain MRI is a well-known fact (the issue of paradoxical embolism) but the high frequency of acute and subacute lesions on brain MRI in the group of patients with a diagnosis of acute PE is surprising.

Association of polymorphisms of platelet receptors GPIa (807C>T), GPVI (13254T>C), and P2Y12 (34C>T and H1/H2 haplotype) with increased risk of periprocedural bleeding in patients undergoing coronary angiography/percutaneous coronary intervention.

INTRODUCTION: Periprocedural bleeding related to coronary angiography (CAG) or percutaneous coronary intervention (PCI) is associated with worse prognosis. Determining genetic variations associated with increased bleeding risk may help to identify high-risk patients. AIM: To analyse the association between single nucleotide polymorphisms (SNPs) of crucial haemostatic platelet receptors (GPIa, GPVI, P2Y12) and the risk of periprocedural bleeding complications related to CAG/PCI. MATERIAL AND METHODS: The population consisted of 73 patients with ischaemic heart disease who developed bleeding complications within 30 days after CAG/PCI and 331 patients without bleeding. The frequency of SNPs of GPIa 807C/T, GPVI 13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype was analysed using polymerase chain reaction (PCR) hybridization methods. RESULTS: The prevalence of variant alleles GPIa 807T, GPVI 13254C, P2Y12 34T, and P2Y12 H2 haplotype in the total study population was 56.7%, 20.3%, 56.2%, and 24.3%, respectively. The presence of variant alleles was not related to increased risk of periprocedural bleeding: GPIa 807C/T (OR = 1.29, 95% CI: 0.75-2.24, p = 0.334), GPVI 12354T/C (OR = 0.82, 95% CI: 0.40-1.64, p = 0.551), P2Y12 34C/T (OR = 0.71, 95% CI: 0.42-1.22, p = 0.189), P2Y12 H1/H2 haplotype (OR = 0.69, 95% CI: 0.35-1.36, p = 0.258). The frequency of the homozygous form of P2Y12 H2 haplotype was higher in the group of patients who developed bleeding (OR = 2.79, 95% CI: 0.51-13.77, p = 0.161). CONCLUSIONS: No significant association of the SNPs of GPIa 807C/T, GPVI 13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype with increased risk of periprocedural bleeding was found in patients with ischaemic heart disease undergoing CAG/PCI.

Number of severe bleeding complications according to classification used: Is unified classification of bleeding complications really necessary?

BACKGROUND: To compare the number of severe periprocedural bleeding complications from the total number of bleeding complications associated with diagnostic selective coronary angiography or percutaneous coronary intervention (PCI) when using different classifications (TIMI, GUSTO, PLATO, BARC) and to relate these classifications to real hemodynamic status of evaluated patients. METHODS: We analyzed data from 106 patients who underwent invasive procedure for ischemic heart disease (selective coronary angiography/PCI) and suffered from any type of bleeding complication. RESULTS: The number of bleeding according to impacts on hemodynamic status and consequent treatment shows that 54.7% of all bleedings did not need any specific therapy. Bleeding leading to death, hemorrhagic shock, hemodynamic instability, administration of blood transfusion, surgical procedure and local treatment occurred in 6.6%, 1.9%, 5.7%, 14.2%, 2.8%, and 14.2%, respectively. The results comparing bleeding classifications demonstrate that the rate of severe bleeding complications may increase up to 4 times when different classifications are used on the same group of patients (TIMI 9.4%, GUSTO 15.1%, PLATO 39.2% and BARC 35.9%). The power of association between severe bleeding determined by these classifications and real hemodynamic compromise using Kendall's tau-c correlation is -0.4106 (95% CI -0.599 to -0.222), -0.5355 (95% CI -0.718 to -0.353), -0.5513 (95% CI -0.729 to -0.374) and -0.7552 (95% CI -0.897 to -0.612) for TIMI, GUSTO, PLATO and BARC, respectively. CONCLUSIONS: The data show significant dependence of percentage of severe periprocedural bleeding complications on selected classification. The strongest association between severe bleeding and real hemodynamic status was found for BARC classification as this classification seems to be promising for future general use.

Troponin T: Correlation with location and volume of acute brain infarction.

BACKGROUND: The troponin T (cTnT) is frequently elevated in acute ischemic stroke (AIS) patients. However, the relationship, if any, between the cTnT level and brain infarction remains to be established. The aim was to investigate the possible correlation between the location and volume of brain infarction and the cardiac cTnT serum level in AIS patients. METHODS: The study consisted of consecutive AIS patients admitted within 12h of stroke onset. The location and volume of the acute ischemic lesion was assessed with magnetic resonance imaging. Standard laboratory tests, including cTnT and repeated electrocardiograms, were performed at admission and after 4h. Correlations between the cTnT level and the location and volume of brain infarction and baseline parameters were tested with a Spearman correlation coefficient. Univariate and multiple logistic regression analysis (LRA) were used to determine the possible predictors of cTnT elevation. RESULTS: Out of the 200 enrolled patients, elevated cTnT was present in 71 (36%). No correlation was found between the cTnT serum levels and the location (P>0.05) nor volume of brain infarction (r=0.05, P=0.48). LRA identified creatinine (OR: 1.26 per 10µmol/L increase; 95% CI: 1.043-1.524), NT-proBNP (OR: 1.05 per 100µg/L increase; 95% CI: 1.018-1.093) and male gender (OR: 3.674; 95% CI: 1.025-13.164) as significant independent predictors of pathological elevation of cTnT. CONCLUSIONS: Although elevated cTnT serum level is relatively frequent in AIS patients within the first 12h of stroke onset, it is not related to the location or volume of brain infarction. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov (No. NCT01541163).

Paroxysmal atrial fibrillation in young cryptogenic ischemic stroke: A 3-week ECG Holter monitoring study.

BACKGROUND: Atrial fibrillation is known very frequent cause of ischemic stroke. Undetected paroxysmal atrial fibrillation (PAF) is thus often considered a possible cause of cryptogenic ischemic stroke (CIS). The aim of this prospective study was to detect PAF using ECG Holter monitoring and determinate whether prolongation of the Holter monitoring to 3 weeks would increase the detection rates of PAF in young CIS patients ≤ 50 years. METHODS: The study set consisted of IS patients ≤ 50 years enrolled in the HISTORY (Heart and Ischemic STrOke Relationship studY) study (NCT01541163). CIS was defined according to the TOAST criteria including the absence of ultrasonographic or angiographic signs of atherosclerosis, vasculitis or dissection. Admission ECG, serum levels of high sensitive Troponin T (hs TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), markers of thrombophilia, transoesophageal echocardiography (TEE) and 24-hour ECG-Holter monitoring were performed in all patients. In case of negative 24-h ECG Holter, an additional 3-weeks monitoring was done. RESULTS: Of the 105 enrolled patients ≤ 50 years, 95 (90%) were identified as cryptogenic (49 males, mean age 39.1 ± 8.2 years). All CIS patients had normal admission ECG. In total, PAF was detected in 9 (9.5%, 95% CI: 3.5% - 17.8%) patients; in two during 24-h ECG Holter and in seven during 3-weeks Holter monitoring. Patients with PAF had more frequently elevated admission hs TnT and NT-proBNP levels (P - 0.0001). CONCLUSIONS: PAF was detected in 9.5% of young CIS patients and 3-weeks ECG Holter monitoring increased the detection rate.

ECG in patients with acute heart failure can predict in-hospital and long-term mortality.

Initial risk stratification in patients with acute heart failure (AHF) is poorly validated. Previous studies tended to evaluate the prognostic significance of only one or two selected ECG parameters. The aim of this study was to evaluate the impact of multiple ECG parameters on mortality in AHF. The Acute Heart Failure Database (AHEAD) registry collected data from 4,153 patients admitted for AHF to seven hospitals with Catheter Laboratory facilities. Clinical variables, heart rate, duration of QRS, QT and QTC intervals, type of rhythm and ST-T segment changes on admission were collected in a web-based database. 12.7 % patients died during hospitalisation, the remainder were discharged and followed for a median of 16.2 months. The most important parameters were a prolonged QRS and a junctional rhythm, which independently predict both in-hospital mortality [QRS > 100 ms, odds ratio (OR) 1.329, 95 % CI 1.052-1.680; junctional rhythm, OR 3.715, 95 % CI 1.748-7.896] and long-term mortality (QRS > 120 ms, OR 1.428, 95 % CI 1.160-1.757; junctional rhythm, OR 2.629, 95 % CI 1.538-4.496). Increased hospitalisation mortality is predicted by ST segment elevation (OR 1.771, 95 % CI 1.383-2.269) and prolonged QTC interval >475 ms (OR 1.483, 95 % CI 1.016-2.164). Presence of atrial fibrillation and bundle branch block is associated with increased unadjusted long-term mortality, but mostly reflects more advanced heart disease, and their predictive significance is attenuated in the multivariate analysis. ECG in patients admitted for acute heart failure carries significant short- and long-term prognostic information, and should be carefully evaluated.

Real time 3-dimensional transesophageal echocardiography is more specific than 2-dimensional TEE in the assessment of left atrial appendage thrombosis.

BACKGROUND: In patients indicated for detection of intraatrial thrombus (T), 2-dimensional transesophageal echocardiography (2DTEE) is routinely used but differentiation between T and trabeculae or artifacts in the left atrial appendage (LAA) is often difficult. AIMS: To compare the diagnostic value of real time 3D-transesophageal echocardiography (RT3DTEE) and 2DTEE in the assessment of LAA thrombosis. PATIENTS AND METHODS: One hundred and ten consecutive patients (73M, aged 64+-13) were examined by 2DTEE. In terms of possible T, individual pts were diagnosed as negative (N2), uncertain trabecular finding (U2), other/artifacts (O2), and clearly positive (T2). The RT3DTEE was then applied and the categorization repeated (N3,U3,O3 and T3, resp.). Finally, the operator decided whether the RT3DTEE. A: had an additional diagnostic value, and/or B: changed the definite diagnosis of thrombosis. RESULTS: N2:71; U2:17; O2:19; T2:3; N3:97; U3:1; O3:12; T3:0. Ad A/ RT3DTEE enabled us to refine or change the diagnosis in 26/110 cases. 17 pts were switched from group U2 to N3, 7:O2-N3 and 2:T2-N3. 12 pts from O2 and 1 pt from T2 remained unclarified. Ad B/ Diagnoses were changed in 6 patients after RT3DTEE. A very suspicious T2 was found in 3 patients. In 1, the finding was requalified definitely as musculi pectinati. In the second patient, the finding was re-categorized as just a spontaneous echocontrast without T. In another 4 patients, T in LAA was definitely excluded after RT3DTEE (1 patient switched from U2 to N3, 3 from O2 to N3). In another 13, the findings remained unclear, mostly because of poor quality image. No real thrombus was found in this study. CONCLUSION: RT3DTEE provides additional information, which may be helpful in the differentiation of thrombus from other findings. It is particularly useful in the identification of muscular trabeculae in the left atrial appendage.

Troponin T in acute ischemic stroke.

Multiple interactions are considered to occur among the various forms of cardiovascular and cerebrovascular diseases. The aim of this study was to assess the serum level profile of cardiac troponin T (cTnT) in patients with acute ischemic stroke (AIS) to evaluate factors associated with increased serum levels of cTnT. Patients with AIS enrolled in this prospective observational study were admitted to the hospital <12 hours after stroke onset. At admission, and 4 hours later, all patients were subjected to neurologic examinations and brain computed tomography or magnetic resonance imaging; standard laboratory tests, including cTnT and other cardiac markers; and repeated electrocardiography. Correlations between cTnT and several baseline parameters were tested, and multivariate regression analysis was used to assess the predictors of cTnT elevation. In total, 107 consecutive patients with AIS (65 men, mean age 67.2 ± 14.2 years) were enrolled. Thirty-nine patients (36.4%) presented with elevated cTnT above the upper limit of normal. The cTnT levels were correlated significantly with age (r = 0.448) and the levels of N-terminal pro-brain natriuretic peptide (r = 0.528), cystatin C (r = 0.457), creatine kinase-MB mass (r = 0.253), urea (r = 0.281), and albumin (r = -0.219). Multiple logistic regression analysis found creatinine >90 µmol/L (odds ratio 3.45, 95% confidence interval 1.09 to 10.85), N-terminal pro-brain natriuretic peptide (odds ratio 100 µg/L increase 1.09, 95% confidence interval 1.03 to 1.16), and creatine kinase-MB mass (odds ratio per 1 µg/L increase 1.45, 95% confidence interval 1.04 to 2.04) were associated with cTnT elevation in patients with AIS. In conclusion, elevated cTnT can be frequently detected in patients with AIS. To reliably identify patients with current acute myocardial impairment, more in-depth clinical investigation is needed.

Assessment of relationship between acute ischemic stroke and heart disease--protocol of a prospective observational trial.

BACKGROUND: Stroke and acute myocardial infarction are the leading causes of death and disability in industrialized countries. Multiple interactions exist between the various forms of cardiovascular and cerebrovascular diseases, and risk factors for development of stroke and major cardiovascular events are similar. There is currently no clear link between acute coronary syndrome and stroke, although it has been repeatedly described. In addition, there are currently no clear recommendations for how to proceed in the case of signs of myocardial damage in patients with acute stroke and how to manage the next follow-up. METHODS-DESIGN: In this prospective observational trial, 500 consecutive ischemic stroke patients admitted at the Comprehensive Stroke Center will be enrolled within 12 h from stroke onset. The set of examinations will consist of: 1) Acute brain computed tomography or magnetic resonance imaging 2) Laboratory tests: A) within 12 h from stroke onset: NT pro B-type of natriuretic peptide, pro-atrial natriuretic peptide, creatinekinase MB, troponin T (cTnT), interleukin 6, procalcitonin, high sensitive C-reactive protein and D-dimers. B) control level of cTnT after 4 h from admission C) non-acute laboratory samples within 60 h from stroke onset: glycated haemoglobine, serum lipids; 3) Electrocardiogram (ECG) on admission and 4 h from stroke onset; 4) Transesophageal or transthoracal echocardiography and 24-h ECG-Holter within 15 days from stroke onset; 5) Neurosonological examination within 60 h from stroke onset; 6) Thirty patients with a positive finding of acute myocardial ischemia (ECG, cTnT) will be examined by coronary angiography (CAG); 7) Epidemiological data will be acquired. STATISTICS: The epidemiological characteristics of the whole sample of patients; correlation between differences between group of cardioembolic ischemic stroke patients and group of patients with ischemic stroke of another etiology; correlation of infarction volume on DWI-MRI with the level of cTnT; correlation of the ECG findings with the level of cTnT and clinical signs; correlation of the CAG findings with level of cTnT and ECG findings will be statistically evaluated at the 5% level of statistical significance. CONCLUSION: The main goal of the project is to improve identification of patients with acute coronary syndrome and with concurrent acute ischemic stroke as these patients require specific treatment and secondary prevention of ischemic events. TRIAL REGISTRATION: Clinicaltrials.gov NCT01541163.