Cognitive changes associated with cerebral emboli during coronary intervention.

OBJECTIVE: To investigate factors influencing the frequency and type of microembolic signals (MES) detected using transcranial Doppler (TCD) in patients undergoing elective coronary intervention, and to correlate MES with silent stroke detected using magnetic resonance imaging (MRI) and cognitive dysfunction. METHODS: The subset study of a randomized clinical trial was conducted on 70 patients (58 males; mean age 59.9 ± 8.4 years) who underwent bilateral TCD monitoring of middle cerebral arteries (MCAs) during elective coronary interventions. Neurologic examination and brain MRI were performed prior to, and 24 h post­intervention. Cognitive function tests were performed prior to, and on day 30 post­intervention. RESULTS: The incidence of detected MES was 94.3 %. Eighteen (25.7 %) patients had new clinically asymptomatic ischemic lesions on MRI. The number of solid MES negatively correlated with changes in revised Addenbrooke's Cognitive Examination test (ACE-R) and, the number of solid MES and combinations of solid and gaseous MES negatively correlated with changes in Mini Mental­State Examination (MMSE) conducted on day 30 after the intervention (p < 0.05 in all cases). CONCLUSION: Cardiac catheterization was associated with a high risk of cerebral embolism in our patients. A higher number of solid MES and combinations of solid and gaseous MES was associated with the deterioration in cognitive tests (Tab. 5, Fig. 3, Ref. 30).

RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.

RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia. Many non-p.R4810K rare variants of RNF213 have been identified in white moyamoya disease patients, although the ethnic mutations have not been investigated in this population. In the present study, we screened for RNF213 variants in 19 Slovakian and Czech moyamoya disease patients. A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic. We previously reported one proband harboring RNF213 p.D4013N. Results from the present study identified four rare variants other than p.D4013N (p.R4019C, p.E4042K, p.V4146A, and p.W4677L) in four of the patients. P.V4146A was determined to be a novel de novo mutation, and p.R4019C and p.E4042K were identified as double mutations inherited on the same allele. P.W4677L, found in two moyamoya disease patients and an unaffected subject in the same pedigree, was a rare single nucleotide polymorphism. Functional analysis showed that RNF213 p.D4013N, p.R4019C and p.V4146A-transfected human umbilical vein endothelial cells displayed significant lowered migration, and RNF213 p.V4146A significantly reduced tube formation, indicating that these are disease-causing mutations. Results from the present study identified RNF213 rare variants in 22.2% (4/18 probands) of Slovakian and Czech moyamoya disease patients, confirming that RNF213 may also be a major causative gene in a relative large population of white patients.

Implementation of ESC-STEMI guidelines into clinical practice: an analysis of the Slovak Registry of Acute Coronary Syndromes (SLOVAKS).

This study analysed the implementation of official European Society of Cardiology (ESC) guidelines for the management of ST elevated myocardial infarction (STEMI) patients. Initiatives were aimed at the education of both healthcare professionals and inhabitants. Changes in clinical practice and clinical outputs were analysed using data acquired from the SLOVak registry of Acute Coronary Syndromes (SLOVAKS). From 2007 to 2008 positive changes were noticed at every level of the 'life chain'. The proportion of patients treated by primary percutaneous coronary intervention (PCI) and by early reperfusion rose significantly. Total ischaemic time was shortened by 12 min in patients treated by thrombolysis and by 26 min in patients treated by PCI. In-hospital lethality for STEMI decreased significantly. The weakest point in the management of STEMI patients in Slovakia was the still-significant time loss incurred by patients themselves. Targeted initiatives aimed at implementing official ESC guidelines can significantly improve clinical outcomes in a relatively short period of time.

Impact of left ventricular ejection fraction on clinical outcomes over five years after infarct-related coronary artery recanalization (from the Occluded Artery Trial [OAT]).

In the Occluded Artery Trial (OAT), percutaneous coronary intervention (PCI) of an infarct-related artery on days 3 to 28 after acute myocardial infarction was of no benefit compared to medical therapy alone. The present analysis was conducted to determine whether PCI might provide benefit to the subgroup of higher risk patients with a depressed ejection fraction (EF). Of 2,185 analyzed patients (age 58.6 +/- 11.0 years) with infarct-related artery occlusion on days 3 to 28 after acute myocardial infarction in the Occluded Artery Trial, 1,094 were assigned to PCI and 1,091 to medical therapy. The primary end point was a composite of death, reinfarction, and New York Heart Association class IV heart failure. The outcomes were analyzed by EF (first tertile, EF < or =44%, vs second and third tertiles combined, EF >44%). Interaction of the treatment effect with EF on the study outcomes were examined using the Cox survival model. The 5-year rates of the primary end point (death, reinfarction, or New York Heart Association class IV heart failure) were not different in either subgroup (PCI vs medical therapy, hazard ratio 1.25, 99% confidence interval 0.83 to 1.88, for EF < or =44%; hazard ratio 0.98, 99% confidence interval 0.64 to 1.50, for EF >44%). However, in patients with an EF >44%, PCI reduced the rate of subsequent revascularization (p = 0.004, interaction p = 0.05). In conclusion, optimal medical therapy remains the overall treatment of choice for stable patients with a persistent total occlusion of the infarct-related artery after acute myocardial infarction, irrespective of the baseline EF. In patients with normal or moderately impaired left ventricular contractility, PCI reduced the need for subsequent revascularization but did not otherwise improve outcomes.

Distribution and determinants of myocardial perfusion grade following late mechanical recanalization of occluded infarct-related arteries postmyocardial infarction: a report from the occluded artery trial.

OBJECTIVE: To evaluate the distribution and determinants of myocardial perfusion grade (MPG) following late recanalization of persistently occluded infarct-related arteries (IRA). BACKGROUND: MPG reflects microvascular integrity. It is an independent prognostic factor following myocardial infarction, but has been studied mainly in the setting of early reperfusion. The occluded artery trial (OAT) enrolled stable patients with persistently occluded IRAs beyond 24 hr and up to 28 days post-MI. METHODS: Myocardial blush was assessed using TIMI MPG grading in 261 patients with TIMI 3 epicardial flow following IRA PCI. Patients demonstrating impaired (0-1) versus preserved (2-3) MPG were compared with regard to baseline clinical and pre-PCI angiographic characteristics. RESULTS: Impaired MPG was observed in 60 of 261 patients (23%). By univariate analysis, impaired MPG was associated with failed fibrinolytic therapy, higher heart rate, lower systolic blood pressure, lower ejection fraction, LAD occlusion, absence of collaterals (P < 0.01) and ST elevation MI, lower diastolic blood pressure, and higher systolic sphericity index (P < 0.05). By multivariable analysis, higher heart rate, LAD occlusion, absence of collaterals and higher systolic sphericity index (P < 0.01), and lower systolic blood pressure (P < 0.05) were independently associated with impaired MPG. CONCLUSION: Preserved microvascular integrity was present in a high proportion of patients following late recanalization of occluded IRAs post-MI. Presence of collaterals was independently associated with preserved MPG and likely accounted for the high frequency of preserved myocardial perfusion in this clinical setting. Impaired MPG was associated with baseline clinical and angiographic features consistent with larger infarct size.