Showing papers by "Aleš Linhart published in 2012"

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization

Abstract: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P = 0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P = 0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. Conclusions Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.)

Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal. “Prague OHCA study”

Abstract: Background: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. Methods: This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines.

Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation.

Abstract: Extracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO. In 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined. CaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%). In a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.

Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study.

Abstract: Background: There is no study focusing on changes in coronary atherosclerosis during dual lipid-lowering therapy with statin and ezetimibe. Methods and Results: Eighty-nine patients with stable angina randomized in a 1:1 ratio to Group A (aggressive therapy: atorvastatin 80mg, ezetimibe 10mg) and Group S (standard therapy) were analyzed. Treatment period was 12 months. Coronary arteries were examined by intravascular ultrasound and virtual histology. We found a decrease in the percent atheroma volume (PAV) (-0.4%) in Group A compared with an increase (+1.4%) in Group S (P=0.014) and this was accompanied by an increased frequency of combined atherosclerosis regression (increased lumen volume+decreased PAV) in group A (40.5%) compared with group S (14.9%) (P=0.007). The target low-density lipoprotein cholesterol level <2mmol/L, presence of at least 4 of 5 atherosclerotic risk factors, and decreased level of vascular cellular adhesive molecule were independent predictors of plaque regression. There were no significant differences in plaque composition between the 2 groups over the study duration. However, during analysis of the 2 groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusions: Dual lipid-lowering therapy starts atherosclerosis regression, but does not lead to significant changes in plaque composition. The continuous shift in plaque from fibro and fibro-fatty to necrotic with calcification was present in both groups. (Circ J 2012; 76: 176-183)

Hypertrophic cardiomyopathy due to the mitochondrial DNA mutation m.3303C>T diagnosed in an adult male.

Abstract: Mitochondrial disorders comprise a heterogeneous group of diseases with multisystem involvement including myocardium. Most cases of mitochondrial cardiomyopathy are associated with myopathy and encephalopathy and are generally present in infancy or childhood. The disease often exhibits a rapid downward course with death frequently occuring within the first year of life. We describe a unique case of hypertrophic cardiomyopathy due to mitochondrial DNA mutation m.3303C >T in the MT-TL1 gene, diagnosed accidentally in a 35-year-old male. The patient initially presented with stroke of assumed cardioembolic origin due to the presence of two interatrial communications associated with mobile aneurysm of the interatrial septum. No other extracardiac manifestations of mitochondrial disorder were observed.

Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction and left ventricular dysfunction: a 24- month follow up study.

Abstract: Objective and background Despite the use of reperfusion therapies, outcomes in patients with large myocardial infarction (MI), late reperfusion and left ventricular (LV) dysfunction are poor. We investigated long-term safety and efficacy of intracoronary injections of autologous bone marrow-derived mononuclear cells (BMNCs). Methods 27 patients with anterior MI (age 59±12 years, mean baseline LV ejection fraction (LVEF) 39±5 %), who underwent percutaneous coronary intervention 4-24 hours after the onset of symptoms, were randomly assigned either to intracoronary BMNCs injection (n=17, BMNCs group, out of which 14 underwent long-term follow-up), or to standard therapy (n=10, Control group). The LVEF, the LV end-diastolic and end-systolic volumes (LVEDV, LVESV) were assessed by echocardiography at discharge, Month 4 and 24. Myocardial perfusion was assessed using SPECT at baseline and Month 4. Results At 24-month, there was no difference in rates of serious clinical events (36 % vs 50 %, p=0.54). At Month 4 LVEF improved to similar extent in both groups (absolute change +5.8 % vs +7.6 %, p=0.75), with similar infarct size reductions (-10.9 % vs -12.2 %, p=0.47). However, at Month 24, LVEF further improved in BMNCs patients (+12 % vs +8.5 %, p=0.03). This effect resulted from a more pronounced reduction in LVESV (-2.6 ml vs -1.8 ml, p=0.26) and a smaller increase in LVEDV (+16.7 ml vs +17.9 ml, p=0.27) suggesting beneficial long-term effects on LV remodeling. Conclusions BMNCs injections in patients with MI and LV dysfunction were associated with a significant improvement of global LVEF during long term follow-up compared to standard therapy (Tab. 3, Fig. 1, Ref. 50). Full Text in PDF www.elis.sk.

Pulmonary arterial hypertension associated with systemic sclerosis in the Czech Republic.

Abstract: Systemic sclerosis (SSc) is an important cause of pulmonary arterial hypertension (PAH), with an estimated prevalence of 7.85–26.7%. Our aim was to estimate the prevalence of PAH among patients with SSc in the Czech Republic and to compare haemodynamics in SSc patients diagnosed with PAH through screening with those diagnosed previously, based on symptoms. During 2007, SSc patients in the Czech Republic, without significant pulmonary function impairment or cardiac disease, underwent screening for PAH with transthoracic echocardiography. Those with a tricuspid regurgitant (TR) jet gradient suggestive of PAH (>30 mmHg) underwent subsequent right heart catheterisation (RHC) to confirm the diagnosis (mean pulmonary arterial pressure, mPAP, ≥25 mmHg; pulmonary capillary wedge pressure, ≤15 mmHg). Haemodynamics in patients diagnosed with PAH in this way were compared with those in patients diagnosed previously, based on symptoms. Two hundred and three SSc patients (mean age, 53.8 ± 13 years; 82.3% women) from 26 rheumatology practices were screened. Among these, 17 had a TR jet gradient >30 mmHg and underwent RHC; PAH was confirmed in six patients. These six patients were found to have significantly lower mPAP than nine patients diagnosed previously with PAH, based on symptoms (31.17 ± 5.56 vs. 46.89 ± 9.48 mmHg, p = 0.0014). Prevalence of PAH in our SSc cohort was 7.08%. SSc patients diagnosed with PAH through screening have less advanced disease in terms of haemodynamics than those with PAH diagnosed previously based on symptoms; their prognosis is therefore likely to be more favourable.

Genetic variation screening of TNNT2 gene in a cohort of patients with hypertrophic and dilated cardiomyopathy.

Abstract: Mutations in troponin T (TNNT2) gene represent the important part of currently identified disease-causing mutations in hypertrophic (HCM) and dilated (DCM) cardiomyopathy. The aim of this study was to analyze TNNT2 gene exons in patients with HCM and DCM diagnosis to improve diagnostic and genetic consultancy in affected families. All 15 exons and their flanking regions of the TNNT2 gene were analyzed by DNA sequence analysis in 174 patients with HCM and DCM diagnosis. We identified genetic variations in TNNT2 exon regions in 56 patients and genetic variations in TNNT2 intron regions in 164 patients. Two patients were found to carry unique mutations in the TNNT2 gene. Limited genetic screening analysis is not suitable for routine testing of disease-causing mutations in patients with HCM and DCM as only individual mutation-positive cases may be identified. Therefore, this approach cannot be recommended for daily clinical practice even though, due to financial constraints, it currently represents the only available strategy in a majority of cardio-centers.

Gender differences in total cholesterol levels in patients with acute heart failure and its importance for short and long time prognosis.

Abstract: The purpose of this study was to evaluate whether there are gender differences in total cholesterol levels in patients with acute heart failure and if there is an association of this parameter with short and long time mortality. Methods. The AHEAD MAIN registry is a database conducted in 7 university hospitals, all with 24 h cath lab service, in 4 cities in the Czech Republic. The database included 4 153 patients hospitalised for acute heart failure in the period 2006–2009. 2 384 patients had a complete record of their total cholesterol levels. 946 females and 1437 males were included in this analysis. According to the admission total cholesterol levels, patients were divided into 5 groups: < 4.50 mmol/l (group A), 4.50–4.99 mmol/l (group B), 5.0–5.49 mmol/l (group C), 5.50–5.99 mmol/l (group D) and > 6.0 mmol/l (group E). The median total cholesterol levels were 4.24 in males and 4.60 in females (P<0.001). There were differences in the distribution of total cholesterol levels between men and women: group A 57.6 vs 45.0%, group B 13.8 vs 16.3%, group C 9.8 vs 12.5%, group D 7.7 vs 11.4%, group E 11.1 vs 14.8% respectively (all P<0.001). The median age of men was 68.7 vs 77.3 years in women (P<0.001). In all total cholesterol categories women were older than men: group A 77.7 vs 69.5 years, group B 78.6 vs 69.1 years, group C 77.3 vs 68.8 years, group D 76.8 vs 64.2 years, group E 75.6 vs 64.4 years (all P<0.001). For the calculation of long term mortality, the cohort was divided into three groups: total cholesterol levels below 4.50 mmol/l, 4.50-5.49 mmol/l and above 5.50 mmol/l. The log rank test was used for the analysis. Results. There were no differences in hospital mortality between male and female in general (9.2 vs 10.8%, P<0.202), or in total cholesterol levels in subgroups. Total cholesterol levels were associated with in-hospital mortality (P<0.002). In the long-term follow up (78 months) patients with total cholesterol levels below 4.5 mmol/l had the worst prognosis (P<0.001). An independent influence of total cholesterol level on mortality and survival was confirmed in the multivariate model as well. Conclusions. Women with acute heart failure had higher total cholesterol levels than men in all ages. There was a higher percentage of women with total cholesterol levels above 6 mmol/l and lower percentage in the group below 4.5 mmol/l than in men. In all, total cholesterol categories women were older than men. Total cholesterol levels are important for in- hospital mortality and long term survival of patients admitted for acute heart failure.

Carotid intima-media thickness in young survivors of acute myocardial infarction

Abstract: BACKGROUND: Carotid intima-media thickness (CIMT) is considered to be a useful surrogate marker of coronary atherosclerosis. However, it is unclear whether this applies to young patients with acute myocardial infarction (AMI), in whom most cases are attributable to the destabilization of focal atheroma.

Coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial extracorporeal membrane oxygenation and intraaortic balloon counterpulsation

Abstract: An extracorporeal membrane oxygenation (ECMO)-based approach is increasingly used in cardiac arrest (CA). However, little is known about coronary perfusion pressure progress over time in CA managed by ECMO. The aim of this study was to assess femorofemoral (FF) compared to femoro-subclavian (FS) venoarterial ECMO in a pig model of prolonged CA on coronary perfusion pressure (CPP), myocardial metabolic recovery and resuscitability.

Impact of antecedent hypertension on outcomes in patients hospitalized with severe forms of acute heart failure.

Abstract: Objective Even though several studies described a positive influence of elevated initial blood pressure on the outcome in acute heart failure (AHF), data specifically addressed to a population with severe AHF associated with antecedent hypertension, regardless of admission blood pressure values, are missing. Methods and results From the 4153 consecutive patients enrolled in the Czech AHF registry we selected 1343 patients who suffered from pulmonary oedema or cardiogenic shock and compared them according to the presence of antecedent hypertension. Demographic, clinical, laboratory, treatment profiles and mortality rates were assessed and predictors of short- and long-term outcome were identified. Patients with antecedent hypertension (n = 1053, 78%) were older (P < 0.001), more often women (P. 0.001), having more co-morbidities and a worse laboratory profile. A trend for worse survival of hypertensive patients was observed when compared to a non-hypertensive cohort (1-, 2-, 3-year survival 70.0, 61.5, 55.5% vs. 72.6, 68.2, 64.0%, P = 0.062). Age and creatinine levels were independently associated with mortality during the whole follow-up period (P < 0.001). Low left ventricular ejection fraction, need of mechanical ventilation, inotropic and vasopressor support, were adversely related to in-hospital mortality (P < 0.001). On the other hand, presence of initial tachycardia improved short-term outcome (P = 0.007). Long-term survival was worsened by initial atrial fibrillation (P = 0.036) and anaemia (P < 0.001) while the presence of de-novo AHF improved it (P = 0.009). Conclusions Long-term antecedent hypertension is not significantly correlated with mortality after an episode of severe AHF, but probably still participates in vascular and end-organ damage. Survival of these patients is determined by other associated co-morbidities.

Hyperinvasive approach to out-of hospital cardiac arrest usingmechanical chest compression device, prehospital intraarrestcooling, extracorporeal life support and early invasiveassessment compared to standard of care. A randomized parallelgroups ...

Abstract: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. Methods This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. Primary outcome 6 months survival with good neurological outcome (Cerebral Performance Category 1–2). Secondary outcomes will include 30 day neurological and cardiac recovery. Discussion Authors introduce and offer a protocol of a proposed randomized study comparing a combined “hyper invasive approach” to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future.

Hybrid myocardial revascularization—the cardiologist's view

Abstract: This article summarizes current knowledge on the mutual position of surgical and interventional treatment of patients with multivessel coronary artery disease. It focuses on the possibilities of their combined use – so called hybrid myocardial revascularization. The use of minimally invasive surgery combined with current technologies of coronary interventions offers new opportunities, taking advantages of both procedures and eliminating some of their disadvantages. This previously rarely used technique could improve the clinical outcomes and treatment comfort in selected groups of patients.