Calcium scoring on coronary computed angiography tomography with photon-counting detector technology: Predictors of performance.

INTRODUCTION: Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy. METHODS: CCTA datasets were acquired with either 120 or 140 â€‹kVp. CAC scores and volumes were calculated from TNC and VNI images in 197 consecutive patients undergoing CCTA. CAC density score, mean volume/lesion, aortic Hounsfield units and standard deviations were then measured. Finally, percentage deviation (VNI - TNC/TNC∗100) of CTA-derived CAC scores from non-enhanced scans was calculated for each patient. Predictors (including anthropometric and acquisition parameters, as well as CAC characteristics) of the degree of discrepancy were evaluated using linear regression analysis. RESULTS: While the agreement between TNC and VNI was substantial (mean bias, 6.6; limits of agreement, 178.5/145.3), a non-negligible proportion of patients (36/197, 18.3%) were falsely reclassified as CAC score â€‹= â€‹0 on VNI. The use of higher tube voltage significantly decreased the percentage deviation relative to TNC-based values (ߠ​= â€‹-0.21 [95%CI: 0.38 to -0.03], p â€‹= â€‹0.020) and a higher CAC density score also proved to be an independent predictor of a smaller difference (ߠ​= â€‹-0.22 [95%CI: 0.37 to -0.07], p â€‹= â€‹0.006). CONCLUSION: The performance of VNI-based calcium scoring may be improved by increased tube voltage protocols, while the accuracy may be compromised for calcified lesions of lower density. The implementation of VNI in clinical routine, however, needs to be preceded by a solution for detecting smaller lesions as well.

The diagnostic accuracy of truncated cardiovascular MR protocols for detecting non-ischemic cardiomyopathies.

Cardiovascular magnetic resonance imaging is one of the most important diagnostic modalities in the evaluation of cardiomyopathies. However, significant limitations are the complex and time-consuming workflows and the need of contrast agents. The aim of this multi-center retrospective study was to assess workflows and diagnostic value of a short, contrast agent-free cardiac magnetic resonance protocol. 160 patients from Heidelberg, Germany and 119 patients from Montreal, Canada with suspected cardiomyopathy and 20 healthy volunteers have been enrolled. Scans were performed at a 1.5Tesla or 3Tesla scanner in Heidelberg and at a 3Tesla scanner in Montreal. We used single-slice T1 map only. A stepwise analysis of images has been performed. The possible differential diagnosis after each step has been defined. T1-values and color-encoded T1 maps significantly contributed to the differential diagnosis in 54% of the cases (161/299); the final diagnosis has been done without late gadolinium enhancement images in 83% of healthy individuals, in 99% of patients with dilated cardiomyopathy, in 93% of amyloidosis patients, in 94% of patients with hypertrophic cardiomyopathy and in 85% of patients with hypertensive heart disease, respectively. Comparing the scan time with (48 ± 7 min) vs. without contrast agent (23 ± 5 min), significant time saving could be reached by the short protocol. Subgroup analysis showed the most additional diagnostic value of T1 maps in amyloidosis and hypertrophic cardiomyopathy or in confirmation of normal findings. In patients with unclear left ventricular hypertrophy, a short, non-contrast protocol can be used for diagnostic decision-making, if the quality of the T1 map is diagnostic, even if only one slice is available.

The role of age in post-cardiac arrest therapy in an elderly patient population.

AIM: We investigated the effect of age on post-cardiac arrest treatment outcomes in an elderly population, based on a local database and a systemic review of the literature. METHODS: Data were collected retrospectively from medical charts and reports. Sixty-one comatose patients, cooled to 32-34 °C for 24 h, were categorized into three groups: younger group (≤65 years), older group (66-75 years), and very old group (>75 years). Circumstances of cardiopulmonary resuscitation (CPR), patients' characteristics, post-resuscitation treatment, hemodynamic monitoring, neurologic outcome and survival were compared across age groups. Kruskal-Wallis test, Chi-square test and binary logistic regression (BLR) were applied. In addition, a literature search of PubMed/Medline database was performed to provide a background. RESULTS: Age was significantly associated with having a cardiac arrest on a monitor and a history of hypertension. No association was found between age and survival or neurologic outcome. Age did not affect hemodynamic parameter changes during target temperature management (TTM), except mean arterial pressure (MAP). Need of catecholamine administration was the highest among very old patients. During the literature review, seven papers were identified. Most studies had a retrospective design and investigated interventions and outcome, but lacked unified age categorization. All studies reported worse survival in the elderly, although old survivors showed a favorable neurologic outcome in most of the cases. CONCLUSION: There is no evidence to support the limitation of post-cardiac arrest therapy in the aging population. Furthermore, additional prospective studies are needed to investigate the characteristics and outcome of post-cardiac arrest therapy in this patient group.

Vitamin D Deficiency Predicts Poor Clinical Outcomes in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND AND AIMS: Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT. METHODS AND RESULTS: We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (p = 0.045) and poor clinical response (p = 0.03) after adjusting to all significant baseline predictors. CONCLUSION: Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.

Platelet impedance adhesiometry: A novel technique for the measurement of platelet adhesion and spreading.

INTRODUCTION: Thrombogenesis plays an important role in today's morbidity and mortality. Antithrombotics are among the most frequently prescribed drugs. Thorough knowledge of platelet function is needed for optimal clinical care. Platelet adhesion is a separate subprocess of platelet thrombus formation; still, no well-standardized technique for the isolated measurement of platelet adhesion exists. Impedimetry is one of the most reliable, state-of-art techniques to analyze cell adhesion, proliferation, viability, and cytotoxicity. We propose impedimetry as a feasible novel method for the isolated measurement of 2 significant platelet functions: adhesion and spreading. METHODS: Laboratory reference platelet agonists (epinephrine, ADP, and collagen) were applied to characterize platelet functions by impedimetry using the xCELLigence SP system. Platelet samples were obtained from 20 healthy patients under no drug therapy. Standard laboratory parameters and clinical patient history were also analyzed. RESULTS: Epinephrine and ADP increased platelet adhesion in a concentration-dependent manner, while collagen tended to have a negative effect. Serum sodium and calcium levels and age had a negative correlation with platelet adhesion induced by epinephrine and ADP, while increased immunoreactivity connected with allergic diseases was associated with increased platelet adhesion induced by epinephrine and ADP. ADP increased platelet spreading in a concentration-dependent manner. CONCLUSION: Impedimetry proved to be a useful and sensitive method for the qualitative and quantitated measurement of platelet adhesion, even differentiating between subgroups of a healthy population. This novel technique is offered as an important method in the further investigation of platelet function.

Left atrial rather than left ventricular impaired mechanics are associated with the pro-fibrotic ST2 marker and outcomes in heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. METHODS AND RESULTS: In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r = -0.30, P = 0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P > 0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P = 0.023). CONCLUSIONS: Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF.

Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: a classical twin study.

BACKGROUND/OBJECTIVES: Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs. SUBJECTS/METHODS: In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models. RESULTS: In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (rMZ=0.81, rDZ=0.32), similar to SAT and VAT quantities (rMZ=0.80, rDZ=0.68 and rMZ=0.79, rDZ=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two. CONCLUSIONS: Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.

Early diastolic septal movement in patients with myocarditis.

AIM: To evaluate early diastolic septal relaxation as a parameter in the diagnostic workup via cardiovascular magnetic resonance imaging (CMRI) in patients with myocarditis. MATERIALS AND METHODS: Early diastolic septal movement was evaluated (EDS) prospectively via frame-by-frame analysis in 255 consecutive patients with presenting signs of myocarditis and in 64 controls matched 4:1 for gender and age. ECG-triggered, T2-weighted, fast spin echo triple inversion recovery sequences and late gadolinium enhancement were obtained, as well as left ventricular (LV) function and dimensions in patients and controls. RESULTS: EDS was detected in 66.7% of the patients and 18.7% of the controls (p<0.001). Sensitivity was 69.4% and specificity 79.7%. Patients with EDS had a significant lower LV ejection fraction (LV-EF) of 61.1±0.6% and significant higher end-diastolic volume (EDV) of 158.5±2.7 ml than in patients without EDS (LV-EF 65.3±0.9%, p=0.0001; EDV 148.4±3.9 ml, p=0.04). A significant negative correlation was observed between LV-EF and EDS in patients, and a lower LV-EF correlated with a more frequent occurrence of EDS (r=-0.24, p=0.0001). Scar tissue was also more frequent in patients than controls (63.1% and 7.8%, p=0.007). CONCLUSIONS: EDS is a parameter obtained non-invasively by CMRI and is present in a high percentage of patients with myocarditis. Cardiac functional parameters are significantly altered in patients with EDS. EDS is a feasible parameter that can play an important role in the diagnosis of myocarditis.

Transradial and transulnar access for iliac artery interventions using sheathless guiding systems: A feasibility study.

PURPOSE: Our aim was to evaluate the acute success and complication rates of the transradial and transulnar access for iliac artery stenting using sheathless guiding systems. METHODS: Clinical and angiographic data from 156 consecutive patients with symptomatic iliac artery stenosis who were treated with transradial or transulnar access were evaluated. All patients underwent Duplex ultrasound before and after the intervention. The primary endpoints were the procedural success rate, major adverse events, and access site complication rates. The secondary endpoints were the angiographic result of the iliac artery intervention, fluoroscopy time, X-ray dose, procedure length, crossover rate to another puncture site and hospitalization duration. The impact of the learning curve was also investigated, along with right or left radial access. RESULTS: The indication for the intervention was intermittent claudication in 109 patients (69.9%), critical limb ischemia in 44 (28.2%) subjects and acute limb ischemia in three individuals (1.9%). Technical success was achieved in 155 patients (99.4%), with a crossover rate of 3.8%. Radial and ulnar artery access was used in 151 (96.8%) and 7 (4.5%) patients, respectively. The Ankle-brachial index increased from 0.69 [0.65-0.72] to 0.91 [0.88-0.95] as a result of the procedures (P < 0.001). The cumulative incidence of major adverse events was 3.8% at the 2-month follow-up (0% in patients with intermittent claudication and 13.8% in patients with critical limb ischemia). Radial artery access site complications were encountered in eight patients (5.1%). We documented decreased X-ray doses (1742.0 [783.9-2701] vs. 1435 [991.1-1879] vs. 692.8 [275.3-1110] Gy cm-2 P < 0.05) over time; however, the fluoroscopy time, procedure time, and contrast consumption were not significantly different. Left hand access was not associated with significantly better results than right radial artery access. CONCLUSIONS: Iliac artery stenting can be safely and effectively performed using radial or ulnar artery access and sheathless guiding catheters, with acceptable complication rates and high levels of technical success. The physician learning curve plays an important role in decreasing the X-ray dose. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Transseptal Leftventricular Endocardial Pacing is an Alternative Technique in Cardiac Resynchronization Therapy. One Year Experience in a High Volume Center.

INTRODUCTION: In patients receiving cardiac resynchronization therapy (CRT), failure rate to implant the left ventricular (LV) lead by the traditional trans-venous approach is 4-8%. Surgical epicardial implantation is considered as an alternative, but this technique is not without morbidity. Evidence from case documentation and from small trial batches demonstrated the viability of endocardial LV lead implantation where surgical epicardial lead placement is not applicable. MATERIAL AND METHODS: Four patients were implanted with endocardial LV lead using the transseptal atrial approach after unsuccessful transvenous implantation. Implantation of an endocardial active fixation LV leads was successful in all patients with stable electrical parameters immediately after implantation and over the follow-up period. All patients received anticoagulation therapy in order to target the international normalized ratio of 2.5-3.5 and have not experienced any thromboembolic, hemorrhagic events, or infection. RESULTS: Follow-up echocardiography indicated significant improvement of LV systolic function (24 + 4.9 to 32 + 5.1 %, P = 0.023) with a notable improvement of the functional status. CONCLUSIONS: Endocardial left ventricular lead implantation can be a valuable and safe alternative technique to enable LV stimulation in high surgical risk patients where standard coronary sinus implant is unsuccessful.

Radiofrequency ablation of focal atrial tachycardia: Benefit of electroanatomical mapping over conventional mapping.

BACKGROUND: Catheter ablation is a proven therapy of focal atrial tachycardia. However limited information is available about the additional value of electroanatomical over conventional mapping methods for this specific arrhythmia. METHODS: Consecutive catheter ablation procedures of FAT were analyzed in two cardiology centres. Only conventional mapping was used in 30 of the 60 procedures whereas additionally CARTO mapping was performed in another 30 procedures. Acute, six-month success rate, and procedural data were analyzed. RESULTS: Localization of ectopic foci is congruent with previously published data. There was no statistically significant difference between procedure time and fluoroscopy time using additionally CARTO mapping, compared to conventional mapping only. Acute success rate was higher in procedures guided by CARTO mapping than in procedures based on conventional mapping (27/30 vs. 18/30, p = 0.0081). During the 6-month follow-up period there was a better outcome (p = 0.045) in case of CARTO guided procedures (success: 11 cases, partial success: 12 cases, failure: 4 cases) compared to conventional mapping (success: 4 cases, partial success: 18 cases, failure: 7 cases). CONCLUSIONS: Catheter ablation of focal atrial tachycardias using the CARTO electroanatomical mapping system seems to provide higher acute and 6-month success rate compared to ablation using conventional mapping methods only.

Safety, clinical outcome, and fracture rate of femoropopliteal stenting using a 4F compatible delivery system.

OBJECTIVE: To determine the safety, clinical outcome, and fracture rate of femoropopliteal interventions using 4F stents. METHODS: Between January 2010 and December 2011, 112 symptomatic patients were treated by stent implantation. Ten patients were lost to follow up; therefore, 102 patients (62 men; mean age 66.4 ± 10.1 years) were retrospectively analyzed. The indication for femoropopliteal revascularization was severe claudication (Rutherford-Becker score = 3) in 63 (62%) patients and chronic critical limb ischemia (Rutherford-Becker score = 4-6) in 39 (38%). Follow up included palpation of peripheral pulses and measurement of ankle brachial index. In patients with suspected in-stent restenosis duplex ultrasonography was performed. In 2013, patients were asked to return for a fluoroscopic examination of the stents. RESULTS: 114 lesions (Trans-Atlantic InterSociety Consensus-C and D, n = 45) were treated with 119 stents (Astron Pulsar, n = 42; Pulsar-18, n = 77). Lesions were long (≥100 mm) in 49 cases and heavily calcified in 35. Stents were long (≥120 mm) in 46 cases. Ten stents were partially overlapped. The technical and clinical success rates were 100%. Two puncture related complications were noted, neither of which required surgical repair. Eleven patients died (myocardial infarction, n = 4; stroke, n = 2; cancer, n = 5) and nine patients underwent major amputation (above knee, n = 4). The primary patency rate was 83% at 6 months and 80% at 12 months. The primary assisted patency rate was 97% at 6 months and 94% at 12 months. The secondary patency rate was 86% at 6 months and 85% at 12 months. The prevalence of fractures was 26% (type III and IV, 10%) after an average follow up of 25 months. CONCLUSION: Femoropopliteal stenting using a 4F compatible delivery system can be accomplished with a low complication rate, acceptable fracture rate, and with similar 12 month patency and revascularization rates as their 6F counterparts.

Clinical implementation of cardiac resynchronization therapy-regional disparities across selected ESC member countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Mesh-covered embolic protection stent implantation in ST-segment-elevation myocardial infarction: final 1-year clinical and angiographic results from the MGUARD for acute ST elevation reperfusion trial

The MGuard, a bare metal stent covered with a polymer mesh, was designed to reduce distal embolization during percutaneous coronary intervention in ST-segment-elevation myocardial infarction. In the MGUARD for Acute ST Elevation Reperfusion trial, the primary end point of complete ST-segment resolution was significantly improved with the MGuard compared with control. We evaluated 1-year clinical and angiographic results.METHODS AND RESULTS:Patients with ST-segment-elevation myocardial infarction ≤12 hours undergoing primary percutaneous coronary intervention of a single de novo native lesion were randomized to the MGuard versus any commercially available metallic stent (39.8% drug-eluting). Clinical follow-up was performed through 1 year, and angiography at 13 months was planned in 50 MGuard patients. There was no difference in major adverse cardiac events (1.8% versus 2.3%; P=0.75) at 30 days between the groups. Major adverse cardiac events at 1 year were higher with the MGuard, driven by greater ischemia-driven target lesion revascularization (8.6% versus 0.9%; P=0.0003). Conversely, mortality tended to be lower with the MGuard at 30 days (0% versus 1.9%; P=0.04) and at 1 year (1.0% versus 3.3%; P=0.09). Late lumen loss at 13 months in the MGuard was 0.99±0.80 mm, and binary restenosis was 31.6%.CONCLUSIONS:In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a trend toward reduced 1-year mortality was present in patients treated with the MGuard stent. Target lesion revascularization and major adverse cardiac events rates during follow-up were higher in the MGuard group than in the control stent group, and angiographic late loss of the MGuard was consistent with that expected from bare metal stents.

Complement activation and its prognostic role in post-cardiac arrest patients.

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 °C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac arrest patients.

Left ventricular untwisting in athlete's heart: key role in early diastolic filling?

Untwisting contributes to left ventricular filling through suction generation. We sought to investigate diastolic function and untwisting dynamics in different forms of left ventricular hypertrophy: in athlete's heart and hypertrophic cardiomyopathy. Elite athletes in kayaking, canoeing and rowing (n=28), patients with hypertrophic cardiomyopathy (HCM, n=15) and healthy sedentary volunteers (n=13) were compared. Left ventricular volumes, wall thickness-to-volume ratio were assessed by cardiac MRI. Following conventional and tissue Doppler measurements, untwist and untwist rate were determined by speckle tracking echocardiography. Wall thickness-to-volume ratio describing remodelling was significantly higher in HCM, but similar in athletes and controls (athlete vs. HCM vs. control: 0.107±0.019 vs. 0.271±0.091 vs. 0.104±0.012 mm×m²/ml, mean±SD, p<0.001). Mitral lateral annulus e' velocity referred to diastolic dysfunction in HCM (15.3±3.6 vs. 7.9±3.3 vs. 15.0±3.0 cm/s, p<0.01). At time point of mitral valve opening, untwist and untwist rate were significantly different: the highest values were measured in athletes, while the lowest were found in HCM (untwist: 51.3±19.1 vs. 11.6±10.4 vs. 35.9±16.3%; untwist rate: -32.5±13.0 vs. -10.6±10.8 vs. -23.0±7.7°/s, p<0.05). Untwisting correlated with E/A, e' and E/e'. Athlete's heart is characterized by increased untwist and untwist rate, which can aid diastolic function. Evaluation of untwisting dynamics may help to distinguish pathological hypertrophy.

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

Cinaciguat prevents neointima formation after arterial injury by decreasing vascular smooth muscle cell migration and proliferation.

AIMS: Vascular smooth muscle cell (VSMC) migration, proliferation and remodeling of the extracellular matrix contribute to lumen loss after arterial injury leading to restenosis. Several studies indicated the role of the cyclic guanosine monophosphate signaling in neointimal formation. Cinaciguat, the novel soluble guanylate cyclase activator, currently being in phase IIb clinical trial, has been shown to exert antiplatelet and anti-remodeling effects in animal models of vascular pathology. In this study we investigated the effects of cinaciguat on post-injury arterial stenosis. METHODS AND RESULTS: Male Sprague-Dawley rats (n=100) underwent endothelial denudation by wire injury of the right common carotid artery. Cinaciguat (10mg/kg/day orally) were administered to 50 rats (1-, 2-, 3-day and 1-, 3-week treatment time), while 50 rats received placebo. A 3-week treatment resulted in a significantly reduced vascular stenosis (17.53 ± 10.84% in the treatment group vs. 43.25 ± 30.83% in the control wire injury group) and neointima/media area ratio (0.45 ± 0.32 in the treatment group vs. 1.09 ± 0.69 in the control wire injury group). By using quantitative real-time PCR, Western blot and immunohistochemistry, matrix-metallopreoteinase-9 (MMP-9) was found to be upregulated in the control-injured carotids over the whole follow-up, and cinaciguat significantly decreased MMP-9 expression by 3 weeks. As assessed by protein immunoblot, injury-induced local decrease of soluble guanylate cyclase ß1 subunit could be recovered by cinaciguat. In vitro wound healing assay with VSMCs revealed dose-dependent antimigratory and antiproliferative effects of cinaciguat. Plasma level of cyclic guanosine monophosphate was significantly elevated after 3 weeks of treatment. CONCLUSION: Our results show that cinaciguat prevents injury-induced neointimal hyperplasia by decreasing VSMC migration and proliferation through the regulation of MMP-9.

Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes.

Foregoing researches made on the N/OFQ system brought up a possible role for this system in cardiovascular regulation. In this study we examined how N/OFQ levels of the blood plasma changed in acute cardiovascular diseases. Three cardiac patient groups were created: enzyme positive acute coronary syndrome (EPACS, n = 10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11). We compared the patients to healthy control subjects (n = 31). We found significantly lower N/OFQ levels in the EPACS [6.86 (6.21-7.38) pg/ml], ENACS [6.97 (6.87-7.01) pg/ml and IHD groups [7.58 (7.23-8.20) pg/ml] compared to the control group [8.86 (7.27-9.83) pg/ml]. A significant correlation was detected between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ depression is in association with the level of ischemic stress and the following inflammatory response. Further investigations are needed to clarify the relevance and elucidate the exact effects of the ischemic stress on the N/OFQ system.

Patchy myocardial pattern of virus sequence persistence in heart transplant recipients--possible role of sampling error in the etiology.

BACKGROUND: The pathway from viral myocarditis to end-stage heart failure is commonly accepted, but diagnosis of virus-mediated myocardial injury remains challenging. Virus persistency in the myocardium may accelerate ventricular failure; thus, a precise diagnosis of virus persistency may prevent the development of end-stage heart failure. METHODS: We performed a systematic investigation on the sampling error of viral diagnostics in heart transplant recipients: Transmural samples from 5 regions of the explanted hearts from recipients during heart transplantation were amplified using entero-, adeno-, and herpesvirus sequences and histologic examinations performed. RESULTS: We examined 175 myocardial samples from dilated cardiomyopathy and 100 samples from 20 forensic medicine patients. Seven patients were positive for the examined viruses: 10 positive regions for adenovirus, and 1 positive region for herpes virus DNA, but none for enterovirus. A focal myocardial pattern was detected for adenovirus. CONCLUSION: Our results with the patchy myocardial viral persistence may explain possible false-negative results related to virus-mediated etiology among end-stage dilated cardiomyopathy patients. Therefore, repeated endomyocardal biopsies, and multiple cardiac samples are recommended to be obtained to evaluate the etiology of heart failure, thus reducing the occurrence of end-stage heart failure and decreasing the number of patients requiring heart transplantation.